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Pattern of CNS anomalies in a population with a high rate of consanguineous marriages
Clinical Genetics
Abstract
Nine thousand six hundred and ten births were prospectively studied in the three major hospitals in Al-Ain, United Arab Emirates (UAE) between October 1995 and January 1997. Babies suspected of, or diagnosed, as having central nervous system (CNS) abnormalities were evaluated by a neonatologist, a clinical geneticist and a pediatric neurologist. Brain computerized tomography/magnetic resonance imaging (CT/MRI) was performed on all babies suspected of having CNS abnormalities. In addition, metabolic screening and chromosome analysis were also performed when indicated. Of the 225 babies with congenital anomalies identified, 31 had CNS abnormalities (3.2/1000). Syndromic abnormalities of the CNS were present in 13 cases (42%), chromosomal abnormalities in one case (3.2%) and the rest included: neural tube defect (NTD) in 11 cases (36%), holoprosencephaly in two cases (6.4%) and hydrocephalus in four cases (12.9%). Detailed analysis of the syndromic types revealed that out of the 13 cases, 12 were inherited as autosomal recessive (AR) and in one case the inheritance was undetermined. Consanguinity with high level of inbreeding was present in 12 cases and the majority of the syndromes identified were extremely rare. The study indicates that CNS anomalies are fairly common in the UAE, particularly, the recessive syndromic types. Careful and detailed analysis of such anomalies is required so that accurate genetic advice can be given.
... In contrast, little is known about the epidemiology of CBMs in non-Western countries. In a study conducted in the United Arab Emirates, Al-Gazali et al. [8] found that 13.8% of all newborns with congenital anomalies had CNS abnormalities. Interestingly; the rate of consanguinity in the group of newborns with CNS anomalies was 38.7% [8]. ...
... In a study conducted in the United Arab Emirates, Al-Gazali et al. [8] found that 13.8% of all newborns with congenital anomalies had CNS abnormalities. Interestingly; the rate of consanguinity in the group of newborns with CNS anomalies was 38.7% [8]. In comparison, our study revealed a significantly higher rate of consanguinity amongst the studied group reaching 76.2%. ...
Congenital brain malformations (CBMs) are a heterogeneous group characterised by abnormal structure of the developing brain. Their aetiology includes in-utero infections, teratogenicity and in a considerable group, genetic causes. Due to the high rate of consanguineous marriages and the possible high prevalence of prenatal infections in Sudan, CBMs are likely to be common. The main aim of this study was to review the clinical profile of children with CBMs attending two main tertiary paediatrics neurology outpatient clinics in Khartoum State, Sudan. Children under the age of 18 years who presented with developmental delay, seizures or abnormal head size were evaluated clinically and with neuroimaging for possible CBMs. Out of 2,114 patients seen within 6 months (September 2016-March 2017) at the Outpatient Departments, 105 patients (5%) were diagnosed with CBMs. Sixty patients (57.1%) had a single brain anomaly, 36 patients (34.1%) had two brain anomalies while nine patients (8.6%) had multiple brain anomalies. Collectively, cortical malformations either isolated or in combination with other anomalies were observed in 37 patients (35.1%), thus by representing the commonest CBMs. Community-based epidemiological studies are needed to ascertain CBMs prevalence, common causes and long-term outcomes.
... Without more detailed data, it is not clear why the Sarawakian indigenous people had higher prevalence than other Malaysians. Some possible reasons include (a) genetic predisposition [16]; (b) being a more rural community with less access to early antenatal care and information, periconceptional folic acid fortification and early antenatal diagnosis and termination of affected pregnancies; and (c) diet preference, with less exposure to food fortified with folic acid. Currently, folic acid fortification of food was voluntary and not mandatory in Malaysia. ...
... The urbanites, which constituted the majority of the Chinese Malaysian and large proportion of the Malays, had more access to such fortified food than communities living in very rural areas of Sarawak, where the road systems were less well developed. Although high rates of consanguinity were reported as an important cause of NTDs in some communities in other countries [16,17], it is not likely a major cause of NTDs among the Sarawakian indigenous people, as consanguineous marriage was not encouraged and practiced commonly. In the present study, there were only a few infants with trisomies, suggesting that this was not a common risk factor associated with NTDs in the Malaysian cohort. ...
Unlabelled:
This study aimed to determine the prevalence and early outcome of neural tube defects (NTDs) in Malaysia. This prospective study included all neonates with NTDs (spina bifida, anencephaly, encephalocoele) born in 2009 in 32 Malaysian hospitals in the Malaysian National Neonatal Network. The prevalence of NTDs was 0.42 per 1000 live births, being highest among the indigenous people of Sarawak (1.09 per 1000 live births) and lowest among Malaysians of Chinese descent (0.09 per 1000 live births). The most common type of NTDs was anencephaly (0.19 per 1000 live births), followed by spina bifida (0.11 per 1000 live births) and encephalocoele (0.07 per 1000 live births). Majority of the infants with anencephaly (94.5%, n = 51), 45.8% (n = 11) with encephalocoele and 9.5% (n = 4) with spina bifida died. The median duration of hospital stay was 4 (range: 0-161) days.
Conclusion:
NTDs were common in Malaysia. Mortality was high. Long-term monitoring of NTD prevalence following folic fortification of food is recommended.
... The neuroradiological hallmark of the disorder is a malformation of the midbrain-hindbrain junction known as the ''molar tooth sign,'' consisting of cerebellar vermis hypoplasia or dysplasia, thick horizontally oriented superior cerebellar peduncles, and abnormally deep interpeduncular fossa. The birth prevalence of this syndrome in the UAE is estimated to be 1 in 5,000 [Al-Gazali et al., 1999]. Forty cases from 17 families with Joubert syndrome were evaluated. ...
... This autosomal recessive syndrome has a birth prevalence of 1/5,000 in the UAE [Al-Gazali et al., 1999], and is known to be common in Kuwaiti Bedouins and Palestinians [Teebi et al., 1992]. One family from the UAE originally from Oman was evaluated [Smith et al., 2006] and found to have a homozygous mutation in mecklin (TMEM67; MKS3) gene (Table 7). ...
The United Arab Emirates inhabitants are ethnically diverse, with ancestries from Arabia, Persia, Baluchistan, and Africa. However, the majority of the current five million inhabitants are expatriates from the Asian subcontinent, Middle Eastern, African, and European countries. Consanguineous marriages within most UAE subpopulations are still the norm, leading to the formation of isolates and higher frequencies of recessive conditions. The UAE is ranked sixth in terms of prevalence of birth defects, with more than 270 genetic disorders reported in the national population. The UAE has high frequencies of blood disorders including thalassemias, sickle cell disease, and G6PD. In addition, certain genetic conditions are relatively common including cystic fibrosis, Joubert, and Meckel syndromes. Furthermore, numerous rare congenital malformations and metabolic disorders have been reported. We review the single gene disorders that have been studied at the molecular level in the UAE (which currently stand at 76) and compile the mutations found. Several novel (p.S2439fs) mutations have been reported including c.7317delA in NF1, c.5C>T (p.A2V) in DKC1, c.1766T>A (p.I589N) in TP63, and c.2117G>T (p.R706L) in VLDLR. We hope that this review will form the basis to establish a UAE mutations database and serve as a model for the collection of mutations of a country.
... 39 The incidence of hydrocephalus was 1.6/1,000 from Al-Madinah Al-Munawarah, Saudi Arabia, 40 0.41/1000 in Al-Ain, UAE. 41 In Hegazy et al, 25 study the percentage of Trisomy-21 among the neurologically impaired was 25.99%. Only 4 cases (0.75/1000) (2 cases encephalocele and 2 cases meningomyelocele) with neural tube defects (NTD) was reported in this study which is lower than that reported by other investigators. ...
... Only 4 cases (0.75/1000) (2 cases encephalocele and 2 cases meningomyelocele) with neural tube defects (NTD) was reported in this study which is lower than that reported by other investigators. The incidence of neural tube defect were 0.82 to 1.6/1000 in Saudi Arabia, 28,42,43 0.78/1000 births in Asir region, Saudi Arabia, 44 1.14/1000 in Al-Ain, UAE, 41 1.3/1000 in Kuwait, 45 1.507/1000 in Bahrain 46 and 1.6/1000 in Shiraz-Iran. 47 The etiology of NTD has been proven to be closely related to folic acid deficiency. ...
To estimate the incidence of major and minor congenital malformations among liveborn infants at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Estimation of risk factors were also evaluated.
Between March 2004 and May 2005, a total of 5356 babies born at King Abdulaziz University Hospital, were enrolled in this study for malformations. Details of cases were recorded after parents' interviews, clinical, radiological, and laboratory evaluations.
One hundred and forty-seven (27.06/1000 livebirth) and 13 (2.39/1000 birth) stillbirth had congenital anomalies. In all livebirth, incidences of major anomalies were 93.9% and minor were 6.1%. Mothers of 95.9% with congenital malformation were healthy, 3.4% were diabetic and 0.7% had cardiac malfomation. In 38.8% of cases parents were consanguineous. Among the liveborn births, the most common system involved was cardiovascular (7.1/1000), followed by musculoskeletal/limb (4.1/1000), external genitalia (2.8/1000), urinary (2.6/1000), multiple chromosomal (2.2/1000), orofacial (1.9/1000), central nervous system (1.9/1000), skin (1.7/1000), multiple single gene (1.3/1000), multiple sequence (0.75/1000), eyes (0.56/1000), unclassified (0.19/1000), musculoskeletal/abdominal (0.19/1000), endocrine (0.19/1000).
High incidence of major malformation in Jeddah. Importance of Genetic Counseling is revealed in our study since more than three quarters of mothers were under 36 years, and may well plan future pregnancies.
... The prevalence of CP in children was 2.8 per 1,000 reported in our study between 2016-2020 was slightly higher than 2.08 in Europe from 2002 (15) Results show similar ranges and that could be due to inherited causes such as genetic microcephaly and other syndromes associated with CP, perhaps due to consanguinity and close relation marriages which is common in the region. (20) There is also a notable increase in multiple births and prematurity related to fertility therapy. (21) Babies born too early are at risk for intraventricular hemorrhage, ie, bleeding in the brain. ...
Objectives:
The aim of this study is to explore the epidemiology (e.g., point prevalence and possible risk factors) as well as the clinical presentation and management of cerebral palsy children who have been seen in a tertiary level children hospital between 2016 and 2020.
Methods:
A proposal has been sent to and approved by Mohammad Bin Rashid University’s Institutional Review Board in March 2021 before the collection and analysis of the data. The approval code is MBRU-IRB-2021-19.
This descriptive cross-sectional study was conducted by collecting and analyzing secondary data of one-hundred cases of cerebral palsy patients. Selected files were of all patients with CP 2016- 2020 and variables included: subtypes of cerebral palsy (spasticity, dyskinesia, or ataxia), gestational age, birth weight, presented symptoms and clinical features, abnormal findings on brain MRI, and prescribed treatment.
Results:
Point prevalence of children with CP was found to be 2.8 per 1,000 admissions during that timeframe, which is slightly higher than that seen worldwide. The patients were aged 1-17 with a mean age of 7.7 years ± 4.28SD, and the most common type of cerebral palsy is spastic diplegic CP making up 32% of the total motor types. The most common abnormal finding on brain MRI was white matter injury of the brain. Furthermore, other known risk factors, including low birth weight and preterm birth were investigated in the study.
Conclusion:
Because of multiple associated conditions and complexities of support needed, management of CP is best done by a multidisciplinary team. Further research on the burden of cerebral palsy in children will help in the monitoring and delivery of cerebral palsy care in the future.
What is already known about this subject?
• Cerebral palsy (CP) is the most common motor disability in childhood with an overall prevalence of 2.11 per 1,000 live births worldwide. (6)
• The prevalence of CP is higher for children born preterm or at low birthweight. (6)
What does this study add?
• This is the first descriptive cross-sectional study to be conducted in Dubai to estimate the point prevalence of cerebral palsy in children.
How might this impact public health and clinical practice?
• This study aims to raise awareness of the condition by providing updated estimates of the burden of the disease, this will help in the monitoring and delivery of cerebral palsy care in the future.
• This study will also act as a base for many researchers to build on in the future.
... In the present study it is found that the most common form of consanguineous marriage was between the first cousins (68%).According to Bittle A H (2001), it is predicted for these cases to have 12.5% of their genes in common that is equivalent to inbreeding coefficient of F ≥ 0.0625 16 . This finding suggests that anencephaly and close relative marriage is strongly associated, similar to other study findings [17][18][19]. The marriage is mostly family decision and arranged linked to significant advantages of consolidation their power and structure. ...
Background: Anencephaly is a type of neural tube defect characterized by abnormal development of the brain and the bones of the skull. Aims: to investigate the association between consanguinity and anencephaly which is the most severe form of neural tube defects and to assess the magnitude of the problem. Methods :A case-control study was conducted between January and December 2014, all women with anencephaly that were admitted to the obstetric department of al Thawra General hospital , Sana'a , were enrolled in this study .The subjects were divided into study ( n = 72 ) and control groups (n=25). Results: From a total of 11283 deliveries, 97 women were having anencephaly giving the overall incidence as 8.5/1000 births. We found significant number (74.2%) of these affected women had consanguineous marriage (95% CI 62.5-83.7; p = 0.0001). The first cousin union was present in (68%). Compared with control, the study cases were characterized by poverty, low education, absence of antenatal care, and mostly from rural setting. Conclusion: Consanguineous marriage is common in our societies and strongly associated with fetal congenital anomalies particularly anencephaly.
... and varies according to the region and sociocultural levels [21]. The consanguinity potentially can increase the risk of fetal NTDs by boosting the risk of autosomal recessive chromosomal dependent syndromes that are responsible for NTDs and central nervous system anomalies [22]. The rate of consanguinity in this study was 19.12% and similar to the rate of pregnancies without fetal NTDs. ...
Objective: To evaluate the risk factors, chromosomal abnormalities and additional anomalies of cases diagnosed with fetal neural tube defects (NTDs). Material and Method: The data of cases diagnosed with fetal NTDs between January 2016 and August 2020 with fetal NTD were retrieved from the hospital database. Only patients whose diagnosis confirmed after pregnancy termination and have a genetic test were included in the study. The family and antenatal history of patients included maternal age, maternal education level, diabetes mellitus, exposed to teratogenic drugs, smoking, and folic acid intake before or during the first trimester, siblings with a congenital abnormality, consanguinity, and AFP MOMs (alpha-fetoprotein, multiple of median) was obtained. Also, the type and level of NTDs and additional anomalies were noted. The data were evaluated using version 23.0 (SPSS Inc., Chicago, IL, USA). Results: During the study period, a total of 68 patients who met the study criteria were included in the study. A total of 27 patients diagnosed with spina bifida, 24 patients with anencephaly and 17 patients with encephalocele. The most anomalies resulted from NTDs was hydrocephaly and pes equinovarus. The most detected chromosomal abnormality was trisomy 13 (3 out of 7), and the most additional anomaly was the cleft lip and palate and detected in 4 (5.88%) patients. Pregestational DM was seen in 12/68 of pregnancies with fetal NTD. Conclusions The rate of additional anomalies and chromosomal abnormalities in cases diagnosed with fetal NTDs is high. Thus, a detailed ultrasonographic examination and genetic tests of fetuses with NTD is essential. The pregnancies complicated with pregestational DM have an increased risk for fetal NTD.
... and varies according to the region and sociocultural levels [21]. The consanguinity potentially can increase the risk of fetal NTDs by boosting the risk of autosomal recessive chromosomal dependent syndromes that are responsible for NTDs and central nervous system anomalies [22]. The rate of consanguinity in this study was 19.12% and similar to the rate of pregnancies without fetal NTDs. ...
Objective: We aimed to evaluate the cervical cerclage treatment among the Syrian refugees with cervical insufficiency. Material and Methods: Retrospective data of 42 Syrian pregnant women who had cervical cerclage suture due to cervical insufficiency between 2015 and 2017 scanned and analyzed with SPSS 22. Results: The mean age of the cases included in the study was 27.4±6.8. 12 cases (28.6%) had spontaneous pregnancy losses twice in the 2nd trimester. 24 cases (57.1%) gave birth via spontaneous vaginal delivery, whereas 18 cases (42.9%) gave birth via cesarean section. A statistically significant difference was determined between pre-cerclage and post-cerclage cervical length. Whilst no difference was detected in pre-cerclage cervical length for deliveries at week 37, a significant difference was detected in post-cerclage length. Conclusıon: Increased miscarriages and second-trimester pregnancy losses seen in the first years of the war especially due to the use of chemical weapons and the stress suffered thereafter as well as the increased reproductive interest after the war bring together a greater desire for a healthy pregnancy and delivery. We believe that cervical-length measurement using transvaginal sonography during post-cerclage checks is important and that measurement of a cervical length equal to or above 30 mm may increase the probability of term delivery and decrease maternal, and most importantly, neonatal complications associated with preterm labor.
... Neural tube defects were the most common types of anomalies seen in Nervous system. The dominance and high frequency of neural tube defects in this study was also reported in previous studies in same geographical areas as in Oman Saudi Arabia (7,23,29), UAE (40)(41)(42)(43), Iran (26,44,45), Pakistan (28,46,47) and India (17,35,(48)(49)(50). Besides, this finding was similar to studies reported by Sawardekar Kiran in 2005, a decade review of major congenital anomalies in Nizwa, Interior provenance, in Oman (51). ...
... Overall, 33.7 % were first cousins, and 20.7% were second cousins 11 . In a study done by Al-Gazali et al. on the patterns of central nervous system anomalies and consanguineous marriages, it was found that a high frequency of the CNS disorders were caused by recessive genes, some disorders being extremely rare and even not mentioned in the literature 12 . In a study carried out by Chandra V the results indicated that consanguinity increases the frequency of rare recessive CNS disorders in a population 13 . ...
... Also, there was an increased clustering of multiple abnormalities and rare recessive disorders in cases with closely related parents and grandparents. 5 Central Nervous System defects like neural tube defects are very common, with an incidence ranging from 1.3/1,000 to 1.6/1,000 in Arab countries (Saudi Arabia, Kuwait, Bahrain, and Iran) 11 and 5.7 /1,000 in India. 12 Spina bifida, the most common neural tube defect, was significantly more frequent among consanguineous parents in many populations, including Saudi Arabian and Indian. ...
Objective: To find out the pattern of different congenital malformation (CM) and to compare the proportion of congenital malformations between consanguineous and non-consanguineous parents. Methodology: This observational study was done in Countess of Dufferin Fund Hospital, (CDF) Hyderabad from July 2006 to June 2008. All newborns with congenital anomaly at birth were included. Complete examination of the newborn after birth and relevant investigations were done. Babies with malformations whose parents were consanguineous were compared with babies having CM whose parents were non-consanguineous. Maternal age, parity, singletons, multiple births, still births and neonatal death were also recorded. Results: Overall prevalence of congenital malformations was 15.7 / 1000 births. Central nervous system anomalies were the commonest (51%). Congenital malformations in the newborns of consanguineous parents were significantly higher than in the newborns of non-consanguineous parents. Still births and neonatal deaths were commoner in the newborns of consanguineous parents. Conclusion: The results of this study show that parental consanguinity is associated with increased congenital malformations; neural tube defect is the most common anomaly seen.
... [33][34][35][36] Similar rates were recorded from The Gulf Cooperation Council (GCC) countries. The incidence was found to be 1.14/1000 in the United Arab Emirates, 37 1.507/1000 in Bahrain, 38 and 1.25/1000 in Oman. 39 An unusually high incidence (3.7-6.96/1000) of NTDs was observed among Egyptians and has been attributed to the high coefficient of inbreeding. ...
This review article discusses the epidemiology, risk factors, prenatal screening, diagnosis, prevention potentials, and epidemiologic impact of neural tube defects (NTDs). The average incidence of NTDs is 1/1000 births, with a marked geographic variation. In the developed countries, the incidence of NTDs has fallen over recent decades. However, it still remains high in the less-developed countries in Latin America, Africa, the Middle East, Asia, and the Far East (>1 to 11/1000 births). Recognized NTDs risks include maternal diabetes, obesity, lower socioeconomic status, hyperthermia, and exposure to certain teratogens during the periconceptional period. Periconceptional folic acid supplementation decreased the prevalence of NTDs by 50-70%, and an obligatory folic acid fortification of food was adopted in several countries to reach women with unplanned pregnancies and those facing social deprivation. Prevention of NTDs can be accelerated if more, especially low income countries, adopted fortification of the staple food in their communities.
... Although the prevalence of consanguineous marriages is relatively low in Europe and the United States (<2% in European countries and <0.2% in the United States), consanguineous marriages between first or second cousins are more common in the Middle East and in Islamic countries (Al-Gazali et al., 1999), where intra-familial unions account for 20 to 50% of all marriages (Tadmouri et al., 2009;Hamamy et al., 2011). First and second cousins marriages are favored among most of the tribes in Saudi Arabia. ...
Background
The role of consanguinity in the etiology of structural birth defects outside of chromosomal and inherited disorders has always been debated. We studied the independent role of consanguinity on birth defects in Saudi women with a high prevalence of consanguineous marriages.Methods
This case and control study was nested within a 3-year prospective cohort study to examine patterns of fetal and neonatal malformations in Saudi women at Prince Sultan Military Medical City (PSMMC), Riyadh -Saudi Arabia. Consanguineous marriages were defined as marriages with first or second cousins (related); unions beyond second cousins (distant relatives) were considered unrelated for this study.ResultsDuring the 3-year study (July 2010 through June 2013), there were 28,646 total births; of these, we included 1,179 babies with major birth defects, and 1,262 babies as their controls. The consanguinity prevalence for all included women was 49.6%. The consanguinity among babies with major Birth Defects (BDs) was 54.5% and 45.2% for controls (P < 0.0002). The prevalence of major birth defects was 41.1 per 1000 total births. Univariate analysis showed that consanguinity had a statistically significant contribution in babies born with genetic syndromes, isolated renal defects, and isolated other defects (P < 0.05). Multivariate logistic regression analyses showed that consanguinity was an independent risk factor for this high prevalence of birth defects in the study population (P < 0.0002).Conclusion
The prevalence of major birth defects in the study population is higher than what is reported from European countries. Consanguinity is a significant independent risk factor for the high prevalence of birth defects. Birth Defects Research (Part A), 2014. © 2014 Wiley Periodicals, Inc.
... As instituições que detém setores de diagnóstico pré-natal se interessam em conhecer a incidência e os padrões dos diferentes tipos de malformações congênitas, determinando o perfil da população à qual a assistência é prestada. Isso viabiliza o planejamento de serviços de saúde adequados a estas condições, e o desenvolvimento de programas de prevenção13 . Neste sentido, ainda, importa atentar para o planejamento de um ambiente onde todos os requisitos sejam atendidos. ...
OBJETIVO: Caracterizar, do ponto de vista sociodemográfico, e obter a evolução pós-natal, das gestantes com diagnóstico ultrassonográfico pré-natal de malformação fetal maior, atendidas no Setor de Medicina Fetal do Hospital das Clínicas (HC) da Faculdade de Medicina da Universidade de São Paulo, entre 15/12/2005 e 15/12/2006. METHODS: Estudo descritivo com 335 gestantes entrevistadas após a obtenção do termo de consentimento pós-informado. Os dados pós-natais foram obtidos mediante contato até um mês após a data provável do parto. Foram excluídas aquelas que não aderiram e que não tiveram confirmação da malformação fetal. RESULTADOS: A idade materna média das gestantes foi de 27,1 anos; a cor da pele predominante parda (48,1%). Em relação à escolaridade, 57,8% das gestantes apresentavam grau de escolaridade igual ou inferior ao ensino médio completo. A renda salarial média foi de 3,1 salários mínimos. Quanto aos antecedentes de malformação fetal, 10,4% das gestantes o referiram. Dentre os casos de malformação atual, as do sistema nervoso central foram as mais prevalentes (28%), seguidas das malformações renais (9,2%) e cardíacas (8,9%). Das gestantes submetidas à pesquisa do cariótipo fetal, 23,6% obtiveram resultados anormais. Em 311 casos (92,8%), o resultado da gestação foi obtido. Destes, 76,8% nasceram vivos; 25,7% evoluíram com óbito neonatal; 16,4% foram natimortos e em 6,3% houve interrupção da gestação. CONCLUSÃO: O presente estudo permitiu conhecer as características sociodemográficas e os resultados gestacionais de mulheres com diagnóstico de malformação fetal, o que poderá ser útil para o planejamento periconcepcional deste grupo de pacientes.
... In part, this may explain the wide variation in the excess incidence of birth defects reported for first cousin progeny, 0.7 to 7.5% greater than in non-consanguineous couples, with the higher values recorded in more recent studies. Congenital defects with a complex aetiology appear to be more common in consanguineous families, 3,18,30,[55][56][57][58][59][60][61][62][63] possibly reflecting rare or even unique recessive mutations, and there is a greater likelihood of recurrence. 64 Many single gene disorders are present at increased prevalence in consanguineous progeny, including autosomal recessive non-syndromal hearing loss, [65][66][67][68][69][70][71] blindness caused by early onset retinal dystrophies, 72-4 childhood glaucoma, and anophthalmos and microphthalmos. ...
... Certain genetic and environmental factors have also been proposed to explain the susceptibility to twinning and NTDs (Garabedian and Fraser, 1994). This explanation is supported by the high incidence of anencephaly in communities with high rates of consanguinity (Zlotogora 1997a,b;Al-Gazali et al., 1999) and by the detection of chromosomal aberrations in spontaneous abortuses with NTD (Coerdt et al., 1997;McFadden and Friedman, 1997). Furthermore, spontaneous abortions are often followed by the term infants with NTD in subsequent pregnancies (Carmi et al., 1994). ...
The incidence rates of anterior neural tube defects, anencephaly and encephalocele appear increased among twins compared with singletons. The current study aimed to evaluate whether the etiology of this phenomenon is related to twinning, assisted reproductive technology (ART), or both.
The study cohort consisted of parturient women who were referred to our ultrasonography unit between January 1998 and December 2009 due to suspicion of severe fetal abnormality. The study cohort was divided into two subgroups based on mode of conception: spontaneous and ART (including IVF and ICSI). The subgroups were further subdivided into singleton and multiple pregnancies. We also compared pregnancies diagnosed with anencephaly in the study group to all live births in the Department of Obstetrics and Gynecology.
Anencephaly was diagnosed in 43 fetuses out of 1154 (3.7%) pregnancies diagnosed with severe fetal anomaly. Anencephaly was diagnosed in 9 out of 78 twin pregnancies (11.5%); of these, 8 of 45 (17.8%) were ART conceived and 1 of 33 (3%) spontaneously conceived. A significant correlation was found between twinning and anencephaly, with an odds ratio (OR) of 3.4 [confidence interval (CI) = 1.3-8.9, P= 0.011], while no significant correlation was found between ART and anencephaly. A significant correlation was found between anencephaly and the combination of ART conception and twinning (OR of 6.6, CI = 2.8-15.3, P< 0.01). Analyzing the distribution of pregnancies diagnosed with anencephaly in the study group compared with the total number of live births in the department revealed a significant correlation between twinning and anencephaly, with an OR of 11.4 (CI = 4.9-26.5, P< 0.01), with no significant correlation between ART and anencephaly. Among all live births, a significant correlation was found between anencephaly and the combination of ART conception and twinning (OR of 24.6, CI = 11.4-53.2, P< 0.01).
Our data suggest that twin pregnancies conceived by ART constitute a high-risk group for anencephaly, due to a possible synergistic effect of twinning and ART.
... Anencephaly was particularly reported more prevalent in communities with high rates of consanguinity. 35 Regarding the NTD sites, the thoracolumbar was the most common site noticed in our NTD cases. This was in agreement with the Western pattern for site distribution, 13 but was in contrast to the North Discussion. ...
To study the incidence, types, and sites of neural tube defects (NTDs) and its associated maternal and environmental variables.
All preterm and full term live and stillborn babies delivered at Al-Ramadi Maternity and Children's Hospital, Al-Anbar Governorate, Iraq, from the 1st of November 2007 to the 1st of November 2008 were examined for gender, gestational age, NTDs, and associated congenital malformations. Mother's data included age, parity, consanguinity, education, antenatal care, previous medical illnesses, other NTDs history, folic acid supplementation, and diagnostic ultrasound. Incidence was calculated per 1000 births.
During the study, 33 infants were delivered with NTDs, giving an incidence of 3.3/1000 births. Most were of myelomeningocele and anencephaly types, and thoracolumbar and lumbosacral sites. Two-thirds of the cases found were from consanguineous marriage, 12 NTD's mothers took folic acid during their pregnancy, while none of them received the drug during the periconceptional period. Three mothers had another NTD affected babies before, and mothers 25-34 years old produced most of the NTD deliveries than any other age groups.
The NTDs incidence is still high compared with developed, and some developing countries. High consanguinity marriage and 100% lack of periconceptional folic acid intake needs further study considerations to reduce such morbid and mortal anomalies.
... The high incidence of autosomal recessive type of dysplasias in our study is probably related to the high level of consanguinity (50% of marriages) in this population (Al-Gazali et al., 1997 ). Previous studies from this region have also shown high rates of malformation caused by recessive genes (Al-Gazali et al., 1995, 1999b). Fibrochondrogenesis was the most common type of bone dysplasia in this study with a birth prevalence of 1.05 per 10,000 births. ...
Define the pattern and birth prevalence of the different types of osteochondrodysplasias in newborn infants in the United Arab Emirates (UAE) population, which is highly inbred and where termination of pregnancy is not accepted.
All infants with a birth weight of 500 gm and above in the three hospitals in Al Ain Medical District of the UAE were studied prospectively over a period of 5 years. For each live birth or stillbirth with suspected skeletal dysplasia, a detailed clinical and radiological examination was carried out. Pregnancy history and information regarding parental age, ethnic origin, family history, and level of consanguinity were obtained and a pedigree was constructed.
Among the 38,048 births during the study period, 36 (9.46/10,000 births) had some type of skeletal dysplasia. Eighteen cases were attributed to autosomal recessive genes (4.7/10,000 births), 10 were due to apparent new dominant mutations (2.62/10,000), five were autosomal dominant type (1.3/10,000) and one was X-linked dominant type (0.26/10,000). In three cases, inheritance was unknown. The most common recessive type of skeletal dysplasia in our series was fibrochondrogenesis (1.05/10,000), followed by chondrodysplasia punctata (0.78/10,000). The birth prevalence rate of skeletal dysplasia doubled in the last 2 years of the 5-year observation period (6.74/10,000 in 1996 vs. 12.86/10,000 in 1999, and 13.45/10,000 in 2000). This increase involved cases caused by new dominant mutations, and occurred mainly in the first half of 1999.
This prospective study has identified a high birth prevalence of skeletal dysplasia, and risk factors are postulated. These findings represent an accurate birthprevalence figure and a useful baseline for this group of birth defects in the UAE.
... In part, this may explain the wide variation in the excess incidence of birth defects reported for first cousin progeny, 0.7 to 7.5% greater than in non-consanguineous couples, with the higher values recorded in more recent studies. Congenital defects with a complex aetiology appear to be more common in consanguineous families, 3,18,30,[55][56][57][58][59][60][61][62][63] possibly reflecting rare or even unique recessive mutations, and there is a greater likelihood of recurrence. 64 Many single gene disorders are present at increased prevalence in consanguineous progeny, including autosomal recessive non-syndromal hearing loss, [65][66][67][68][69][70][71] blindness caused by early onset retinal dystrophies, 72-4 childhood glaucoma, and anophthalmos and microphthalmos. ...
... Anencephalic offspring surviving to term die at birth or soon after (Pinar 2004) thus a pattern of inheritance cannot be established. Anencephaly is reported to be particularly more prevalent in certain communities with a high rate of consanguinity (Zlotogora 1997a,b; Al-Gazali et al. 1999). Spontaneous abortuses with NTD have a significant association with chromosomal aberrations suggesting a genetic component to their etiology (Coerdt et al. 1997; McFadden & Friedman 1997). ...
Spina bifida, anencephaly, and encephalocele are commonly grouped together and termed neural tube defects (NTD). Failure of closure of the neural tube during development results in anencephaly or spina bifida aperta but encephaloceles are possibly post-closure defects. NTD are associated with a number of other central nervous system (CNS) and non-neural malformations. Racial, geographic and seasonal variations seem to affect their incidence. Etiology of NTD is unknown. Most of the non-syndromic NTD are of multifactorial origin. Recent in vitro and in vivo studies have highlighted the molecular mechanisms of neurulation in vertebrates but the morphologic development of human neural tube is poorly understood. A multisite closure theory, extrapolated directly from mouse experiments highlighted the clinical relevance of closure mechanisms to human NTD. Animal models, such as circle tail, curly tail, loop tail, shrm and numerous knockouts provide some insight into the mechanisms of NTD. Also available in the literature are a plethora of chemically induced preclosure and a few post-closure models of NTD, which highlight the fact that CNS malformations are of hetergeneitic nature. No Mendelian pattern of inheritance has been reported. Association with single gene defects, enhanced recurrence risk among siblings, and a higher frequency in twins than in singletons indicate the presence of a strong genetic contribution to the etiology of NTD. Non-availability of families with a significant number of NTD cases makes research into genetic causation of NTD difficult. Case reports and epidemiologic studies have implicated a number of chemicals, widely differing therapeutic drugs, environmental contaminants, pollutants, infectious agents, and solvents. Maternal hyperthermia, use of valproate by epileptic women during pregnancy, deficiency and excess of certain nutrients and chronic maternal diseases (e.g. diabetes mellitus) are reported to cause a manifold increase in the incidence of NTD. A host of suspected teratogens are also available in the literature. The UK and Hungarian studies showed that periconceptional supplementation of women with folate (FA) reduces significantly both the first occurrence and recurrence of NTD in the offspring. This led to mandatory periconceptional FA supplementation in a number of countries. Encouraged by the results of clinical studies, numerous laboratory investigations focused on the genes involved in the FA, vitamin B12 and homocysteine metabolism during neural tube development. As of today no clinical or experimental study has provided unequivocal evidence for a definitive role for any of these genes in the causation of NTD suggesting that a multitude of genes, growth factors and receptors interact in controlling neural tube development by yet unknown mechanisms. Future studies must address issues of gene-gene, gene-nutrient and gene-environment interactions in the pathogenesis of NTD.
... All items for the survey instrument, except sociodemographic and food frequency items, were based on existing research related to congenital anomalies, NTDs, and folic acid (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37). Because no food frequency or diet assessment tool had been used before with Honduran women, the investigators developed a new instrument from tools previously used by experts in the United States (Dr. ...
This study had two purposes: first, to determine the knowledge, attitudes, and practices related to folic acid and birth defects among a convenience sample of postpartum Honduran women; and second, to identify food consumption patterns in this population and determine high-consumption staples for potential folic acid fortification.
Convenience sampling methodology was used to recruit potential study participants. Participants for this study were 2 619 postpartum Honduran women who had had a normal, in-hospital delivery in one of 16 public hospitals located throughout the country or the two social security hospitals that provide services to the Honduran working class population. Over a 10-month period, in-depth, face-to-face oral interviews, supervised by the research coordinator and staff, were conducted in-hospital prior to discharge.
The majority of the women were between 16 and 29 years of age. Approximately half of the respondents (46.4%) had heard of folic acid and over one-third (37.6%) knew that it was a vitamin related to preventing birth defects. Birth defects were most often attributed to drug and alcohol use (20.6%) and lack of vitamin intake (18.1%), but 23.0% related defects to mystical, mythical, or religious causes. Aside from red beans, oranges, and natural fruit juices, folate-rich foods are not widely consumed by this population. The highest consumption frequency of staple foods with the potential to be fortified with folic acid were rice, white flour, corn flour, and pasta.
Results from this study provide potential avenues for food fortification, as well as underscore the need for further education about the role of folic acid in the prevention of neural tube defects. Results highlight that standardized health education for Honduran women of reproductive age is needed if folic acid consumption through fortification and supplementation is to be successful and sustainable.
Congenital anomalies are increasing among low and middle-income countries. Only a few old data are available in the middle-east and in countries where genetic counseling is not implemented through the program of natal care. Our search was to estimate the proportion of congenital brain malformation in the Arab world and to evaluate the related risk factor in each country. Results indicated that Egypt and Tunisia have the highest percentage of congenital brain anomalies with the male proportion being higher than females. Consanguinity marriage and family history are recognized as the most important risk factors for increasing the malformations proportions together with genetic counseling unavailability and in the absence of the modern equipment techniques for chromosomal alterations follow-up. Education, prenatal, natal, and postnatal follow-up are critical for families with a history of congenital anomalies and specifically in cultures where consanguinity marriage is predominant.
Electrodiagnostic studies are considered an extension of the clinical examination for peripheral nervous system diseases and injuries. They have been used routinely to evaluate damaged peripheral nerve function, regardless of etiology. At present, electrodiagnostic evaluation is a very useful tool in peripheral nerve surgery during pre- and intraoperative evaluations and postoperative follow-up. Different techniques are available to assess the functional status of nerves including nerve conduction studies, electromyography, and somatosensory and motor evoked potentials. All of these techniques may be used intraoperatively, in addition to nerve action potential recording and direct electrical nerve stimulation, to evaluate the neural pathways in real time for the resection of intrinsic or extrinsic tumors that affect peripheral nerves. Hence, by using them in tumor resection, the surgeon optimizes the results by diminishing the potential risk of damage during nerve trunk manipulation of healthy fascicles. This chapter examines the general aspects of current monitoring techniques and their intraoperative use for peripheral nerve surgery in tumor resection.
Neurofibromatosis 1 has an incidence of 1 in 2600 to 3000 individuals and represents the most frequent form of neurofibromatosis. Inherited from parents in 50% of cases and consequent to de novo mutations in the remaining half, it is an age-penetrating disorder that affects many of the body systems and in particular the nervous system; lifelong follow-up is necessary to monitor the development of clinical manifestations. Due to its numerous implications and challenging complexity, NF management should preferably be the prerogative of multidisciplinary specialist clinics. NF referral centres should also have an active role in providing education to patients and their families as well as in enforcing prevention strategies.
Clinical and molecular characterization of neuro‐genetic disorders among UAE national patients seen in the Genetic Clinic at Tawam hospital over a period of 3 years. A retrospective chart review of all Emirati patients assessed by clinical geneticists due to neuro‐genetic disorders including global developmental delay, ASD, ID, ADHD, and epilepsy in combination with abnormalities of other organ systems. Each patient had proper assessment including detailed history, three‐generation family history, developmental history and detailed physical examination looking for other system involvement. Hearing test and ophthalmological examination were performed when needed. Magnetic resonance imaging (MRI) of the brain, echocardiogram, and renal ultrasound were pursued as indicated. Detailed psychological evaluation and psychometric assessment were done when indicated. The review was done for a period between January 2018 and December 2020. Genetic investigations included chromosome karyotype, FISH study, metabolic/biochemical tests, chromosome microarray, gene sequencing, targeted mutation testing, trio whole exome and trio genome sequencing. A total of 644 patients with developmental delay, ID, learning difficulty, ASD, ADHD, or NNDs, were seen in genetic clinic from January 2018 to December 2020. A total of 506 patients were included in this review, all completed the genetic evaluations during the study period. There were 398 (61.8%) males and 246 (38.2%) females, with a ratio of 1.6:1. Positive family history of NDD was documented in 132 families, while 115 families had negative history and family history was unknown/unclear in the remaining. Fifty seven (11.26% [57/506]) patients had positive microarray results. Hundred ninety seven (38.9% [197/506]) patients had positive molecular testing. Genetic disorders were found in 133 (67.5% [133/197]) and inborn errors of metabolism were found in 42 (21.3% [42/197]). Consanguinity was documented in 139 patients with positive molecular diagnoses (139/197, 70.5%). Sixty nine (35% [69/197]) patients had autosomal dominant disorders, majority were De Novo (84%). Ninety‐five (48% [95/197]) patients had autosomal recessive diseases, 40 mutations involved inborn errors of metabolism and 50 mutations involved genetic disorders. Pathogenic variants causing both autosomal dominant and recessive disorders were found in 98 patients (49.7% [98/197]), likely pathogenic variants causing both autosomal dominant and recessive disorders were found in 66 patients (33.5% [66/197]). X‐linked related disorders were found in 10 patients (5% [10/197]). Mitochondrial mutation was found in one patient. Novel mutations were found in 76 patients (76/197 i.e., 38.56%). Twenty two patients had variants of unknown significant. The remaining 252 studied patients (252/506 i.e., 49.8%), remained undiagnosed. This study shows that neuro‐genetic disorders in the UAE are very heterogeneous at clinical and molecular levels. Using microarray, WES and WGS a diagnosis was reached in 50% of the patients while no diagnosis was reached in other half of the studied patients. It is possible that some mutations were missed by WGS and WES. However, it is also possible that many of disorders in UAE population are novel and the causative mutation is not yet discovered. More researches need to be done in this population to uncover the molecular basis of these disorders.
Background:
Consanguineous marriages are common in the Middle East including the Gulf countries. The rate of consanguinity in Qatar is approximately 54%, which are mainly first cousins' marriages. Previous studies showed that consanguinity increases the prevalence of birth defects and other genetic disorders. Thus, we studied the effects of consanguinity in a cohort of subjects with certain genetic disorders in Qatar.
Methods:
This cross-sectional study was conducted at two centers in Qatar (Hamad Medical Corporation "HMC" and Shafallah "SC") including 599 Qatari families with certain types of genetic and nongenetic anomalies.
Results:
Consanguineous marriages were seen in 397 of 599 (66.2%) Qatari families and first cousin group counts for 65% in Qatari population. In the total cohort and at HMC, all consanguineous marriages had a significantly higher risk of Autosomal Recessive disorders than nonconsanguineous marriages (total cohort: odds ratio (OR) = 1.72; 95% CI: 1.10, 2.71; p = .02; HMC: OR = 2.98; 95% CI: 1.37, 6.09; p = .005). On the other hand, at HMC, nonconsanguinity was significantly related to chromosomal abnormality (OR = 6.36; 95% CI: 1.13, 35.85; p = .036).
Conclusion:
Our data suggest a significant role of parental consanguinity in increasing the prevalence of genetic disorders; mainly Autosomal Recessive disorders. Chromosomal abnormality disorders were significantly higher among nonconsanguineous marriages. These results help better inform policy makers on social, educational, and public health initiatives that might mitigate the impact of genetic disease in the Qatari society.
Background: Birth defects are an important contributor to infant morbidity and mortality among all racial/ethnic groups, and the 3rd leading cause of infant mortality after cancer and accidents in developed countries
Objective: To estimate the incidence of major and minor birth defects at birth and trying to identify some of possible associated factors.
Methods: Between the 1st of February/2009 and the end of October/2009, 1494 newborns were enrolled in this study in Al- Ramadi Maternity and Children Teaching Hospital was examined for birth defects. Full information regarding the mother, newborn, and some socio-demographic factors were recorded after interview of the mother, and full examination was done by the investigator.
Results: Forty-seven newborns (31.46/1000 total birth) had birth defects. The incidence of major anomalies was 16.73 /1000 total birth and minor 14.73/1000 total birth. Among total births, the most common system involved was genitourinary system (27.7%), followed by central nervous system (19.2%), musculoskeletal system (19.2%), oral anomalies (6.4%), skin (6.4%), and then the others. The incidence of birth defects was significantly higher in preterm infants, low birth weight infants, babies who were breech in utero, and in babies of mothers in both extreme age (below 20 and above 35 years), or had bleeding during pregnancy, urinary tract infection during pregnancy, and polyhydramnios or oligohydramnios.
Conclusion: The incidence of birth defects is alarmingly high in Al- Ramadi city. The catastrophically successive wars imposed on Iraq undoubtedly have played some role in this problem. Attention should be made for defects at birth in genitourinary system, central nervous system and musculoskeletal system, however defects of cardiovascular system, and internal gastrointestinal tract may be evident sometime after birth.
Objective:
To assess fetal abnormalities leading to termination of pregnancy (TOP) performed in twin pregnancies.
Method:
The current study consisted of all women with dichorionic twin pregnancies (study group) who underwent TOP due to fetal abnormalities in our institute from 1999 to 2015. The data were compared to our registry of all parturient women with a singleton pregnancy (control group) that underwent TOP due to fetal anomalies at the same period.
Results:
There were 2495 cases of TOP because of fetal indications during the study period. Of them, 86 (3.4%) and 2409 (96.6%) were from the study and control group, respectively. Structural anomalies were the leading indication for TOP in twins compared with singleton pregnancies (81.4% versus 50.9%, respectively, p < 0.0001). For twins, the leading indication for TOP was central nervous system (CNS) abnormalities and it was more common compared with singleton pregnancies (26.1% versus 12.2%, respectively, p < 0.0001). This was followed by chromosomal/genetic abnormalities (16.3% versus 40.4%, respectively, p < 0.0001).
Conclusions:
We found a different distribution for fetal anomalies leading to TOP in twins versus singleton pregnancies. The main indication for TOP in the study group was structural malformations, with a predominance of CNS abnormalities.
Background
There is no available data from Sudan reflecting the magnitude of the neurological disorders and disabilities in the pediatric age-group. This study aims to evaluate the pattern of neurological disorders among Sudanese children.
Patients and Methods
This is a retrospective survey of children with epilepsy and other neurodisability disorders seen at pediatric neurology outpatient clinic, during the period from January 2007 to August 2013. The data of 9600 patients were analyzed.
Results
A total of 6019 patients were included in the study. The majority of the patients had epilepsy that amounted to 52.8%, followed by cerebral palsy (19.1%), congenital anomalies of the central nervous system (6.2%), neuromuscular disorders (3.2%), stroke (2.4%), ataxia and movement disorders (1.9%), assumed genetic syndromes (1.2%), and others.
Conclusion
Neurological disorders constitute a major cause of chronic morbidity in pediatric age-group.
The United Arab Emirates (UAE) was founded in 1971 as a federation of seven emirates on the Arabian Gulf. It is bounded by Qatar on the northwest, Saudi Arabia on the west and southwest, Oman on the east and northeast, and the Arabian Gulf on the north. It occupies an area of 83,600 km2 and Abu Dhabi is the capital of the state. Six of the emirates lie on the southern shore of the Arabian Gulf and present a continuous coastline stretching some 600 km. The six emirates in geographical order from west to east are Abu Dhabi (which comprises 87% of the entire area of the UAE), Dubai, Sharjah, Ajman, Um Al-Quween, and Ras Al Khaimah. Fujairah is the only emirate without a coastline on the Arabian Gulf; it lies entirely on the Gulf of Oman. © Springer-Verlag Berlin Heidelberg 2010. All rights are reserved.
Objective:
The study investigated the effect of flurbiprofen on the development of anencephaly in early stage chicken embryos.
Material and methods:
We looked at four groups with a total of 36 embryos. There was a control group, a normal saline group, a normal-dose group and a high-dose group with ten, ten, eight and eight eggs with embryo respectively.
Results:
Two embryos in the control group, studied with light microscopy at 48 h, were consistent with 28-29 hours' incubation in the Hamburger-Hamilton System. They had open neural tubes. The other embryos in this group were considered normal. One embryo in the normal saline group was on the occlusion stage at 48 h. One embryo showed an open neural tube. They were compatible with 28-29 hours' incubation in the Hamburger-Hamilton system. The remaining eight embryos showed normal development. In the normal dose group, one embryo showed underdevelopment of the embryonic disc and the embryo was dead. In four embryos, the neural tubes were open. One cranial malformation was found that was complicated with anencephaly in one embryo. In two embryos the neural tubes were closed, as they showed normal development, and they reached their expected stages according to the Hamburger-Hamilton classification. There was no malformation or growth retardation. Four experimental embryos were anencephalic in the high dose group, and three embryos had open neural tubes. One embryo exhibited both anencephaly and a neural tube closure defect. None of the embryos in this group showed normal development.
Conclusions:
Even the usual therapeutic doses of flurbiprofen increased the risk of neural tube defect. Flurbiprofen was found to significantly increase the risk of anencephaly. The provision of improved technical materials and studies with larger sample sizes will reveal the stage of morphological disruption during the development of embryos.
Incidence rates of congenital disorders among the 350 million inhabitants of Arab countries could be influenced via the people's demographic and cultural characteristics. Arabs usually marry at a young age and have large families. They share certain core cultural values and beliefs, with the family accepted as the central structure of society. Consanguineous marriage is favored and respected in most if not all Arab communities, and intrafamilial unions currently account for 20-50% of all marriages. First-cousin unions are especially popular and constitute almost one quarter of all marriages in many Arab countries. Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a considerable proportion of all birth defects among Arabs. Arab geneticists, with their persistent commitment to advancing research, have contributed to the description of a number of rare and new AR syndromes with the identification of novel genes. The collaboration with research teams in high-income countries resulted in a plethora of data on pathogenic variants and their function in causing dysmorphic syndromes. There could still be a considerable number of rare dysmorphic syndromes that prevail among Arabs which are not hitherto described and whose underlying molecular pathologies are not yet defined. Arab countries should thus strive to deploy DNA diagnostics and to build research capability around local priorities. Furthermore, a characterization of the prevailing genetic disorders in each geographic location, together with their mutations, is needed to plan for appropriate screening and testing protocols. An overview of consanguinity in Arab countries and examples of dysmorphology syndromes associated with consanguinity with their available molecular bases will be discussed. © 2014 S. Karger AG, Basel.
The aim of the study was to investigate the relationship between consanguineous marriage and marital adjustment in Turkey. Despite the fact that most studies emphasized the negative genetic effects of consanguineous marriage, a group of people in Turkey still prefer this type of marriage. In addition to the relationship between consanguineous marriage and marital adjustment, extended family relations were also studied. The Dyadic Adjustment Scale and Extended Family Relationship Form were administered to 150 married individuals (75 female and 75 male). Of the participants, 68 were in a consanguineous marriage and 82 nonconsanguineous marriage. The sample was selected by purposive sampling. The result showed that the consanguineous marriage group had significantly lower marital adjustment and had more conflict with extended family than the nonconsanguineous marriage group. The finding is discussed in the context of research and practice.
The effects of consanguineous marriages through genes have strong impacts not only on human capital, but also on political stability through the process that consanguineous marriages alter the sociological structure. Nevertheless, these types of marriages were abandoned by the developed nations at the beginning of the 19th century, although these types of marriages are prefered today in many Asian and African countries. In these countries, the traditional structure could not be broken; a twosome structure is created within the country, within cities, within different regions as well as between regions and between countries. Political stability fails to be achieved in these countries. The twosome structure promotes political instability and bad economic peformances. It is observed that, the countries with high consanguineous marriages experience different sociological and economic factors so that the motives towards individualism considered as an important source of industrial development fail to flourish. An important result of the twosome structure is on human capital investments and on economic development. We followed a different approach in analyzing economic development in accordance with consanguineous marriage and political instability in accordance with human capital investments and economic development. In the study, we analyzed 53 countries; we collected and compiled most recent data of consanguineous marriages, literacy rates and political risk as an indicator of political instability. We calculated GDP per capita growth rates between 1900 and 2003. We grouped countries according to their consanguineous marriage rates. Empirical results show that, the group of developed economies overcome consanguineous marriages before 1900 and achieved political stability, high human capital investments and steady growth rates. On the other hand, the countries practicing high consanguineous marriage rates are less immune to political instability and experience negative growth rates and very low human capital investments. The group of countries that lowered their consanguineous marriage rates below 10 % just before 1980, achieved very rapid economic growth afterwards. Empirical analysis based on factor analysis, correlation and covariance matrices suggest that countries with high consanguineous marriages experience high political instability and fall behind in the process of economic development.
The consanguine marriages and/or causine marriages are generally accepted and evaluated in light of the genetic problems. However, in the study, we aim to explain the effects on economic development and genetics problem of consanguine marriages and to investigate the relationship between economic development, consanguine marriages and genetics. The first part of the study focuses on economic development, consanguine marriages, genetic structure and human capital relations in theoretical framework. The second part contains the econometric analyses, Panel Neural Network investigated.
In our study, development experiences towards economic development are investigated to provide an alternative analysis of economic development, human capital and genetic inheritance in light of consanguineous marriages. The countries analyzed in the study are discussed in accordance with consanguineous marriages. Neural network and panel data analysis are used for analysis of the relationship among consanguineous marriage, economic development, human capital and infant mortality. The results provide empirical findings suggesting that the negative effects of consanguineous marriages and infant mortality on economic development cannot be rejected for the analyzed countries, whereas the negative impact significantly increases for the analyzed African countries.
Arabs are a Semitic people basically defined as individuals speaking Arabic as their native tongue, although with many different dialects, who self-identify as being of Arab ancestry. The Arab world extends from Iraq and the Gulf States in the east to Morocco and Mauritania on the Atlantic coast of North Africa in the west, and through time it has incorporated many populations with ancestral origins outside the Arabian Peninsula. Large Arab communities are now permanent residents in Western Europe, North and South America, and Australia, and so the global Arab population is estimated to number 300–350 million (Hamamy and Bittles 2009).
An essential guide to this major contemporary issue, Consanguinity in Context is a uniquely comprehensive account of intra-familial marriage. Detailed information on past and present religious, social, and legal practices and prohibitions is presented as a backdrop to the preferences and beliefs of the 1100+ million people in consanguineous unions. Chapters on population genetics, and the role of consanguinity in reproductive behaviour and genetic variation, set the scene for critical analyses of the influence of consanguinity in the early years of life. The discussion on consanguinity and disorders of adulthood is the first review of its kind and is particularly relevant given the ageing of the global population. Incest is treated as a separate issue, with historical and present-day examples examined. The final three chapters deal in detail with practical issues, including genetic testing, education and counselling, national and international legislation and imperatives, and the future of consanguineous marriage worldwide.
In this study, development experiences toward economic development are investigated to provide an alternative analysis of economic development, human capital, and genetic inheritance in the light of consanguineous marriages. The countries analyzed in the study are discussed in accordance with consanguineous marriage practices and classified by their per capita gross domestic product (GDP) growth. A broad range of countries are analyzed in the study. Arab countries that experienced high rates of growth in their gross national income during the twentieth century but failed to fulfill adequate development measures as reflected in the growth in national income, countries undergoing transition from tight government regulation to free market democracy, and African nations that have experienced complications in the process of development show important differences in the process of economic development. It is shown that the countries that have reached high average development within the context of per capita GDP have overcome problems integral to consanguineous marriage.
The purpose of this study is to describe the socio demographic profile and perinatal outcome of pregnant women with prenatal ultrasound diagnosis of major fetal malformation at the Hospital das Clínicas, Medical School, São Paulo University. The study was performed from December 15th 2005 to December 15th 2006.
This is an observational descriptive study where 335 pregnant women were interviewed after agreement. Postnatal information was obtained until a month after due date of birth. Cases that were not confirmed and did not consent to participate in the study were excluded.
Mean maternal age was 27.1 years and skin color was brown in 48.1% of cases. According to the education level and salary, 57.8% did not finish college and the mean monthly income was 3.1 minimal wages. A previous history of fetal malformation was reported by 10.4% of women. The central nervous system was the most frequent site of malformation (28.1%), followed by renal (9.3%) and cardiac (9%) defects. Fetal karyotype results were abnormal in 23.6% of fetuses. Pregnancy outcome was ascertained in 311 cases (92.8%): 76.8% were alive, 25.7% were neonatal deaths, 16.4% were stillborn and 6.3% miscarried.
This study describes social demographic features and perinatal outcome in pregnancies with major fetal malformation diagnosed antenatally. This information is useful for parent counseling in cases with an abnormal fetal diagnosis.
To describe the presentation and genetic transmission of ciliary dyskinesia syndrome associated with hydrocephalus and mental retardation in 3 generations of a family.
A large Jordanian family included 9 individuals in 3 generations with recurrent pulmonary infections; 4 male siblings have been diagnosed as having mental retardation, and a maternal uncle was believed to have been similarly affected. Chromosome analysis of the family showed a normal karyotype.
Electron microscopy of the nasal cilia from 3 affected siblings showed features of primary ciliary dyskinesia. Computed tomographic scans of the brains of all 4 affected siblings showed hydrocephalus.
The recurrent pulmonary infections and hydrocephalus in this large Jordanian family are likely related to ciliary dyskinesia, which appears to follow an autosomal recessive mode of inheritance. The unusual presentation of ciliary dyskinesia, hydrocephalus, and mental retardation may be due to a new genetic mutation.
The aim of this study was to determine the level of knowledge and use of periconceptional folic acid supplementation in a sample of postpartum women recruited from three hospitals.
Cross-sectional survey in which a structured questionnaire was used in a face-to-face encounter between the subject and a trained nurse.
Two teaching hospitals associated with Faculty of Medicine and Health Sciences and one private hospital.
Postpartum women in the three hospitals were recruited during a 40-day period in November 1999. Women who did not agree to participate, had complicated labor, delivered babies with congenital malformations, or were too exhausted or difficult to examine, were excluded.
Univariate analyses showed that overall 46.4% of the respondents had heard about folic acid and only 8.7% knew that it prevented birth defects. 45.5% of respondents took folic acid in the first trimester. The percentage of women who had ever heard about folic acid was higher in those with higher education, and those who were not UAE nationals. Use of folic acid was associated with non-UAE nationality.
Awareness of the value of periconceptional folic acid was very low and use of folic acid was less prevalent among women of UAE nationality.
To assess the level of understanding of genetic advice given in the Genetic Clinic and attitudes toward consanguineous marriages, and prenatal, abortion and preconception diagnoses.
One hundred couples underwent structured interviews, and various social and educational data, reason for referral and diagnosis and advice given were recorded. Three months later, the couples were asked open-ended questions about the perceived causation of the disease, recurrence risk, plans for births, and prenatal, abortion and preconception diagnoses.
Half of the couples acknowledged a genetic basis for their child's condition but only 10 remembered the risk given to them. There was a high correlation between educational level and remembering the risk, and the number of healthy children and future plans for further children. Almost half preferred consanguineous marriages and only 10% agreed with prenatal diagnosis and abortion, while 75% agreed with carrier screening and preconception diagnosis in affected families.
Effective genetic counseling in this community requires an informed educated population and introduction of carrier screening and preconception diagnosis in affected families.
The UAE society is cosmopolitan, but the indigenous inhabitants are traditional with puritanical values despite their exposure to other vastly different cultures and habits. Marriages between consanguineous couples are still the norm rather than the exception. As a result, there is a high frequency of genetic disorders, particularly autosomal recessive types. Despite the high frequency of genetic disorders like haemoglobinopathies and others characteristically found in this population, genetic services are inadequate. Screening for certain disorders like thalassaemia are not applied on a wide scale. Abortion is illegal, and therefore, prenatal diagnosis or preconception tests are not done. With the absence of a good national database, deficiency of genetic services and absence of preventative alternatives for carrier couples, genetic counsellors find it difficult to advice pragmatic solutions to issues relating to genetic diseases. This paper reviews common genetic problems in the UAE with special emphasis on available genetic services and support to families with children with inherited disorders. Existing barriers to the improvement of clinical services by prenatal counselling are also discussed.
In Iran, Primary Health care (PHC) has been a main approach to control of communicable diseases over past thirty years. This approach drastically improved main health indices including Infant Mortality Rate (IMR) in Iran. The experience has had two main impacts on the health situation of the country. Firstly community control of health burden of communicable diseases and secondly, bringing about opportunities to non-communicable diseases including genetic disorders to emerge. Past three decades have been also a determining era for profound progress in basic genetic knowledge and development of community tools for prevention and control of genetic and congenital disorders in the world. These advances will widen the gaps between developing countries that are already lacking of basic genetic knowledge and technologies and developed countries that own these capacities, unless there are clever designing to employ the opportunities to bridge the gaps. Iran has enjoyed its first experience of using community tools for control of one of its prevalent genetic health problem, thalassemia major, adopting primary health care approach. This article explains the expansion of the concept and the approach to community control of genetic and congenital disorders and that, how this concept is leading the country to fill the gap of ge-netic knowledge.
An infant with the characteristic phenotype of classical rhizomelic chondrodysplasia punctata was found to have an isolated deficiency of the peroxisomal enzyme acyl CoA dihydroxyacetone phosphate acyltransferase (DHAP-AT). All other peroxisomal functions measured were found to be normal. Previously described in one other case report, this confirms the existence of another distinct form of peroxisomal disorder characterised biochemically by a deficiency in de novo plasmalogen biosynthesis only.
This study examines the frequency of consanguineous marriage and the coefficient of inbreeding in the United Arab Emirates (UAE). The study was conducted in Al Ain and Dubai cities between October 1994 and March 1995. A sample of 2033 married UAE females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and the degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (50.5%) with a coefficient of inbreeding of 0.0222. The commonest type of consanguineous marriage was between first cousins (26.2%). Double first cousin marriages were common (3.5%) compared to other populations. The consanguinity rate in the UAE has increased from 39% to 50.5% in one generation. The level of consanguinity was higher in Al Ain (54.2%) than in Dubai (40%).
To verify and investigate the reported decline of neural tube defects (NTDs) in the last decade, data from three different sources were examined: the Birth Defects Monitoring Program (BDMP), composed of newborn discharge diagnoses; the population-base Metropolitan Atlanta Congenital Defects Program (MACDP); and the National Center for Health Statistics (NCHS), whose data include only live births. Although the three systems use different methods of ascertaining cases, all data bases showed a decreasing trend in NTD rates, with annual percent decreases of 3.1% for NCHS, 5.7% for BDMP, and 7.7% for MACDP. The decrease was noted in all variables examined: race, sex, and birth status for each defect. NTD rates appear to be declining more rapidly in females than in males. Further, the rate among stillborn infants decreased more than the rate among liveborn infants. The exclusion of stillbirths in the NCHS data may contribute to its low rate of decline for female anencephalics. Data from England showed a larger average annual decrease (10.6%) than did data from the United States. Although reasons for the overall decline are not verifiable, a variety of explanations are suggested for this decline and for the difference in NTD rate decline noted between live births and stillbirths. The overall decline in NTD rates should be investigated with respect to etiology; recognition of the decline is useful for planning and evaluating health care programs.
A total of 1633 cases of neural tube defects were analysed, registered between 1980 and 1983 in liveborn and stillborn babies and in fetuses aborted as a result of prenatal diagnosis of malformation in 16 EUROCAT Registries (total births =766 603). A clear geographical pattern was observed. The highest neural tube defect (NTD) rates were seen in Dublin (Ireland), Belfast (UK) and Glasgow (UK) with 40 cases per 10 000 births and in these centres there was a significant decrease in prevalence over the years. In Galway (Ireland) and Liverpool (UK), the rates were approximately 20 cases per 10 000 births, the rate decreasing over years in Liverpool. In the registries situated in continental Europe, the prevalence varied between 6 and 13 cases per 10 000 births and there was no apparent change in the prevalence with time. The spina bifida/anencephaly ratio and the male proportion among the NTD cases were both lower in the British Istes than in continental Europe. Cases of prenatal diagnosis of NTD resulting in termination of pregnancy formed 19% of the total NTD cases, this proportion increasing over years. A large variation between centres was seen in the effectiveness of prenatal screening for NTD.
Smith et al [1980] described two brothers with mental retardation, short stature, and unusual facial appearance. Here we describe an unrelated male who resides in the same institution and who appears to have the same condition. This syndrome is probably inherited in an autosomal or X-linked recessive manner.
In a hospital-based study of almost 174,000 total births during 1968–1976, the authors found the incidence of congenital hydrocephalus to be 66 cases per 100,000 births. There was a significantly higher frequency in children born to mothers who themselves had been born in Puerto Rico but no significant difference in incidence between whites and blacks. The influences of maternal age, previous pregnancies, socioeconomic status, temporal and other factors are assessed and compared to previous reports.
A prospective study of 4934 babies of different ethnic groups has confirmed the high perinatal mortality rate for Pakistanis and has shown that this was not due to a reluctance to terminate a fetus who is known to be seriously malformed. The major cause of early mortality was a high rate of lethal malformations, which occurred in about 1 in 100 Pakistani babies and which accounted for about half of their perinatal mortality. Many of these were autosomal recessive and occurred only in the offspring of consanguineous parents. However, there was also an excess of lethal cardiac malformations which were not associated with parental consanguinity. The remainder of the excess perinatal mortality was probably due to socio-economic factors. These causes are partly amenable to preventive measures, such as the referral of Pakistani women for expert ultrasonography at 18 to 20 weeks of pregnancy.
A prospective study of 4934 babies of different ethnic groups has confirmed the high perinatal mortality rate for Pakistanis and has shown that this was not due to a reluctance to terminate a fetus who is known to be seriously malformed. The major cause of early mortality was a high rate of lethal malformations, which occurred in about 1 in 100 Pakistani babies and which accounted for about half of their perinatal mortality. Many of these were autosomal recessive and occurred only in the offspring of consanguineous parents. However, there was also an excess of lethal cardiac malformations which were not associated with parental consanguinity. The remainder of the excess perinatal mortality was probably due to socio-economic factors. These causes are partly amenable to preventive measures, such as the referral of Pakistani women for expert ultrasonography at 18 to 20 weeks of pregnancy.
We present characteristics of four major congenital neurologic malformations--anencephaly, spina bifida, encephaloceles, and hydrocephalus--from a population of 763, 364 live-born and still-born infants born from 1971 through 1987. During the 17-year study period, 275 infants had anencephaly (0.36 per 1000 total births), 526 had spina bifida (0.69 per 1000 total births), 112 had encephaloceles (0.15 per 1000 total births), and 370 had hydrocephalus (0.48 per 1000 total births). There was a female preponderance of infants with anencephaly, spina bifida, and encephaloceles, while males predominated among those with hydrocephalus. We found declining incidences of anencephaly, spina bifida, and encephaloceles only among white females. Black infants were significantly less likely than white infants or infants of other races to have spina bifida. Twenty percent of infants with anencephaly had congenital anomalies unrelated to the primary defect, as did 40% with encephaloceles, 37% with hydrocephalus, and 22% with spina bifida. Because the racial background of the patient population closely resembles that of the United States as a whole, the features of the malformations described may reflect those of the country.
The aetiology of infantile hydrocephalus (IH) was studied in a population-based series of 61 children with IH born 1967-82 at less than 37 weeks of gestation. A prenatal origin was present in 17 children (28%), a pre- and perinatal in 17 (28%), a perinatal in 26 (43%) and a postnatal in one (1%). The predominant single cause was postaemorrhagic IH, which was diagnosed in 19 (31%). In addition, an undiagnosed cerebral haemorrhage was considered to be the cause in another 25%. The outcome differed between pathogenetic groups. Children with a clear onset of IH (pre-, peri- or postnatal) were found to be at high risk for early death or multiple impairments. Sixteen of 39 (41%) within these groups had died before 2 years of age and 18 of the 23 (78%) survivors showed major neurological dysfunction. This contrasted to no mortality and 41% major dysfunction in children with a less clear onset of IH. A new subgroup consisting of infants born before 28 weeks of gestation emerged in the early 1980s. All infants with IH in this group developed a severe multihandicap condition.
The aetiology of infantile hydrocephalus (IH) was studied in a population-based series of 141 children with IH, born at term in southwestern Sweden 1967-82. A prenatal aetiology was present in 81 children (57%), a pre- and perinatal in 6 (4%), a perinatal in 27 (19%), and a postnatal in 8 (6%); the origin in 19 children (13%) remained untraceable. A variety of aetiologies were revealed or indicated among prenatal conditions. The dominant intrauterine infection was toxoplasmosis. The predominant perinatal condition was posthaemorrhagic IH. The broad outline of outcome differed between pathogenetic groups. Children with a clear prenatal onset of IH were found to be at high risk for early death or multiple neurological impairments. Thirteen of 63 (21%) within this group had died before 2 years of age and 34 of the 50 (68%) survivors showed major neurological dysfunction. This contrasted to the incidences of 3% deaths and 30% sequelae in children with IH of other onset.
The overall incidence of severe congenital abnormalities diagnosed within the first week of life was 12.9/1000, which is similar to other surveys (1,2), although the distribution and type of abnormalities encountered varied considerably. The incidence of spina bifida and encephaloceles was lower than elsewhere (0.54/1000).
We have analysed the cause of perinatal deaths in four hospitals in the North West Thames region over a six year period commencing January 1980. The Pakistani population had a significantly greater perinatal mortality rate (15.7/1000 births) than the Europeans (11.3/1000 births). This was due to an increased incidence of macerated stillbirths and lethal malformations, the latter resulting from a significantly higher incidence of autosomal recessive disorders, neural tube defects, and renal malformations.
The livebirth prevalence of infantile simple hydrocephalus (IH) was investigated in a Swedish population-based survey. The study comprised all liveborn infants with IH apparent before the age of one year and born in the study area between 1967-82. A total of 202 infants fulfilled these criteria; of these, 141 (70%) were born at term and 61 (30%) were preterm. The mean prevalence was 0.53 per 1,000, with a slightly increasing trend from 0.48 in 1967-70 to 0.63 in 1979-82. The increase was entirely referable to the preterm group, in which the prevalence rose from 0.13 per 1,000 in 1967-70 to 0.30 in 1979-82. There was no tendency to an increase in the term group. In 12 of 23 children born very preterm the origin of the IH was a diagnosed cerebral haemorrhage. This is compatible with the increased risk of the latter condition that has been found in very preterm newborns. The mortality among children with IH was highest before the age of one year (15%), after which it was 1.2% per year.
Within the framework of a retrospective epidemiological investigation concerning the incidence of CNS-malformations in the city of Cologne during the period 1971-80, 76 749 hospital births assessed from records in six hospitals were considered. This represents 88% of all hospital births. The incidence varied between 0.79-1.80 with a mean of 1.37/1000 total births. This figure was primarily influenced by the values obtained from Spina bifida (0,59/1000). If the dates for the period 1961-70 are included, a marginal increment is exhibited (from 1.13 up to 1.37/1000) for the total occurrence of CNS-births, as opposed to a slight decrease for the Sb-group (0,65 down to 0.59/1000). A seasonal variation was not revealed for the total number of births. Contrary to worldwide literature, the male rates were significantly higher (113 : 100). The stillbirth-rate was 23,8% compared to 0,63% of total births, whereby hydrocephalus cases with 52% were heavily represented. A relationship between mother's age and incidence of occurrence was, as in the previous decade, not substantiated.
Since the dates presented are obtained on the basis of hospital obstetrics records, it is unlikely that similar figures will arise in future studies, due to improved prenatal diagnosis (sonography and amniocentesis), which influence decisions relating to the possibilities of interruption of pregnancy.
Detailed analysis is presented on the dramatic decline in spina bifida births and other congenital central nervous system defects in the past 12 years, in both Sheffield and the rest of Great Britain. In Sheffield, there was an average of 20 spina bifida births per year up to 1972, but since then there has been a progressive fall to only one in 1984. This decrease may be partly attributable to antenatal diagnosis and terminations of affected pregnancies, but there is no known explanation for the rest of the fall, which has also been experienced throughout Great Britain. The virtual elimination of spina bifida is now possible, as long as the existing methods of prevention and antenatal diagnostic facilities are used even more fully. Relaxation of our effort and a reverse in the 'natural' trend could bring the incidence of spina bifida back to where it was 15 years ago.
Five probable cases of Meckel's syndrome have been ascertained retrospectively through the Leicestershire Perinatal Mortality Survey for the years 1976 to 1982. All of these babies were born to Hindu parents originating from the Gujarat State in India, suggesting that Meckel's syndrome is particularly common among this ethnic group, with a gene frequency of approximately 0.028.
A study of the epidemiology of neural tube defects in the Liverpool and Bootle areas between 1961 and 1979 showed a decline from 1974 onwards. This trend was highly significant and was more marked for anencephaly than for spina bifida. From 1977 to 1979, seventeen pregnancies were terminated for neural tube defects, but this number was too small to have an appreciable effect on incidence. No single factor can be implicated to explain this observation.
We report here retrospective data on 991 liveborn and stillborn infants with neural tube defects (NTDs) born to Utah residents from January 1, 1940 to December 31, 1979. Data were obtained from multiple sources including approximately 1.25 million vital statistics records and several hundred physician and hospital charts. Causal heterogeneity among NTD patients is presumed because 6% of our cases have other congenital anomalies not part of the NTD field defect. A significant association of NTDs with oral clefts is noted. Sex ratios and empiric recurrence risks for isolated NTDs and NTDs associated with other major malformations are also calculated.
The spina bifida rate in Sweden from 1947 to 1981 has been studied using various sources of information, including two central computerised registers. During the period the rate approximately halved, but the decline was not smooth and occurred in three "waves." When the geographical location of high risk areas within each wave was studied, they were found to differ. The findings are discussed in the light of an environmental aetiology hypothesis of this malformation.
Data obtained from routine sources showed that from 1971 to 1982 the birth prevalences of spina bifida and anencephaly in Scotland fell. When known terminations after routine alpha fetoprotein screening were added to total births the adjusted birth prevalence could be calculated. In 1974-82 this fell by 40% for spina bifida (3 X 0-1 X 8) and 36% for anencephaly (2 X 2-1 X 4). These findings were compared with data on birth prevalences in England and Wales, Northern Ireland, and Glasgow. The fall in birth prevalences of spina bifida and anencephaly over the past decade appears to have been due both to a true fall in incidence as well as to increased screening and termination for these conditions.
The birth prevalence of CNS malformations in the region of Krakow from 1979 to 1981 was determined to be 1.26/1000 from records of all live- and still-birth deliveries. The frequency of anencephaly was 0.23/1,000; spina bifida and encephalocele, 0.70/1000; isolated hydrocephaly, 0.26/1,000; and other CNS anomalies, 0.06/1,000. The observed rates are below the median European level.
Female preponderance was found among the probands with anencephaly, encephalomeningocele, and myelomeningocele.
Cytogenetic examination of 35 newborns with CNS malformations documented normal karyotypes in all neonates.
The analysis of seasonal distribution of proband's birthdate and of date of mother's last menstrual period showed no significant seasonal trend.
The epidemiology of neural tube defects was reviewed, using data from two birth defects surveillance systems: the nationwide Birth Defects Monitoring Program and the Metropolitan Atlanta Congenital Defects Program, for 1970-1978 and 1968-1979, respectively. After excluding cases with recognized causes, neural tube defects were divided into two major groups: "singles" and "multiples," depending on the presence of associated major defects. Only singles, which accounted for the majority of cases, were shown to have the well-known epidemiologic characteristics of neural tube defects: marked predominance of females and whites, geographic variation with an east-to-west gradient, and decreasing rates over time. On the other hand, multiples had no excess of females and occurred less predominantly in whites; moreover, their rates showed no geographic variation and little or no downward trends over time. The presence of associated defects indicates that neural tube defects are epidemiologically and probably etiologically heterogeneous. It is suggested that analytic studies of neural tube defects may be more rewarding if they try to identify different risk factors associated with various subgroups. This approach to the study of birth defects may provide better clues to their etiology and pathogenesis.
To verify and investigate the reported decline of neural tube defects (NTDs) in the last decade, data from three different sources were examined: the Birth Defects Monitoring Program (BDMP), composed of newborn discharge diagnoses; the population-base Metropolitan Atlanta Congenital Defects Program (MACDP); and the National Center for Health Statistics (NCHS), whose data include only live births. Although the three systems use different methods of ascertaining cases, all data bases showed a decreasing trend in NTD rates, with annual percent decreases of 3.1% for NCHS, 5.7% for BDMP, and 7.7% for MACDP. The decrease was noted in all variables examined: race, sex, and birth status for each defect. NTD rates appear to be declining more rapidly in females than in males. Further, the rate among stillborn infants decreased more than the rate among live-born infants. The exclusion of stillbirths in the NCHS data may contribute to its low rate of decline for female anencephalics. Data from England showed a larger average annual decrease (10.6%) than did data from the United States. Although reasons for the overall decline are not verifiable, a variety of explanations are suggested for this decline and for the difference in NTD rate decline noted between live births and stillbirths. The overall decline in NTD rates should be investigated with respect to etiology; recognition of the decline is useful for planning and evaluating health care programs.
We previously reported that among neural tube defects (NTDs) with no known causes the ones that occur alone (singles) have different epidemiologic characteristics from those that occur in combination with other defects (multiples), suggesting an underlying causal heterogeneity. In this study, we compared family histories of 223 single NTD cases and 66 multiple cases ascertained through the Metropolitan Atlanta Congenital Defects Program (MACDP) between 1970 and 1979. Compared with siblings of multiples, siblings of singles had a higher precurrence rate for NTDs (2.0% vs. 0.0%) and for birth defects in general (10.9% vs. 3.0%). Furthermore, siblings of singles that were born within 2 years before the birth of the index case had a higher precurrence rate for NTDs (8.0% vs. 1.1%) and for major birth defects (20.0% vs. 2.9%) than had those born earlier. These results further suggest that NTDs are etiologically heterogeneous, depending on the presence of associated defects, and point to important environmental influences in the increased risk for birth defects among siblings of singles. Larger studies are needed to confirm these data and show that single and multiple NTDs have different recurrence rates, not only for NTDs but also for other birth defects.
In a hospital-based study of almost 174,000 total births during 1968--1976, the authors found the incidence of congenital hydrocephalus to be 66 cases per 100,000 births. There was a significantly higher frequency in children born to mothers who themselves had been born in Puerto Rico but no significant difference in incidence between whites and blacks. The influences of maternal age, previous pregnancies, socioeconomic status, temporal and other factors are assessed and compared to previous reports.
Elucidating the cause of disease is often not easy and may require answers to many questions. Perhaps the most important questions have been rather simply stated in verse by Rudyard Kipling.1
I keep six honest serving men;
(They taught me all I knew)
Their names are What and Why and When and How and Where and Who.
In terms of neural tube defects, many of these servants of Mr Kipling have provided valuable epidemiologic clues as to the cause of neural tube defects (NTDs),2 but the specific mechanism responsible for this disabling birth defect has so far escaped definition.
A boy aged 21 months who was being investigated for developmental delay and failure to thrive was found to have punctate epiphyseal calcification. He had no evidence of rhizomelic shortening of the limbs or cataracts. Investigation revealed defective plasmalogen synthesis due to isolated deficiency of dihydroxyacetonephosphate acyltransferase (DHAP-AT). The parents were consanguineous and a sister was similarly affected, suggesting autosomal recessive inheritance. Hitherto, recessively inherited isolated DHAP-AT deficiency has only been described in patients with a phenotype similar to that of rhizomelic chondrodysplasia punctata. This report indicates that the same biochemical disorder can be associated with a less severe phenotype.
The aim of this study was to establish the profile of major congenital malformations in the United Arab Emirates (UAE) population which has a high rate of consanguinity. All births with birth weight above 500 g in the three hospitals in the Al Ain Medical District of UAE were prospectively studied from January 1992 to January 1994. About 98% of the births in the district occur in these three hospitals. Detailed family history and clinical and relevant laboratory investigations were recorded in each case. Necropsy was not permitted. The major malformations were classified as multiple or isolated single system abnormalities as well as genetic or non-genetic disorders. Of the 16,419 births which occurred during the two year period, 173 (10.5/1000 births) had major malformations, 90 (52%) had multiple malformations, and 83 (47.97%) had involvement of a single system. Of the infants with multiple malformations, 43 had recognised syndromes, most of which are autosomal recessive disorders with a high frequency of rare syndromes. Twenty eight (31%) had chromosomal abnormalities. The most common systems involved in infants with isolated single system malformations include gastrointestinal (33), central nervous system (17), and cardiovascular (10). While the consanguinity rate was similar (57% v 54%), the frequency of first cousin marriages was much higher (51% v 30%) in the study group compared with the figures for the general population. The consanguinity rate was highest among the syndrome cases, and related parents were more likely to have infants with multiple malformations than an isolated single system abnormality with a relative risk of 1.69 (95% CL 1.27-2.24). Genetic factors could be implicated in 116 (67%) of the 173 cases of major malformations and 49 (28%) were potentially preventable. The study suggests that genetic disorders account for a significant proportion of congenital malformation in the UAE and, thus, a genetic service should be provided as part of the preventive cae programme.
Prevention of major physical malformations would represent a significant reduction in the burden of mortality and morbidity in infants and young children. However, preventive and therapeutic approaches must be based on a clear understanding of underlying pathogenic mechanisms. While it is estimated that single gene defects account for up to 10% of cases of major malformation, relatively few of these have been identified and analysed in detail. The recognition of characteristic patterns of developmental anomalies associated with specific enzyme defects has highlighted the important role of the metabolic environment in normal development and offers the possibility of correlating biochemical abnormalities with particular teratogenic effects. Once it is generally appreciated that some forms of structural malformation have a specific biochemical basis, metabolic studies should be performed more often in patients with major developmental anomalies. This should lead to identification of other examples of diseases of this type and the elucidation of molecular mechanisms of human teratogenesis.
Kuwait has a cosmopolitan population of 1.7 million, mostly Arabs. This population is a mosaic of large and small minorities representing most Arab communities. In general, Kuwait's population is characterized by a rapid rate of growth, large family size, high rates of consanguineous marriages within the Arab communities with low frequency of intermarriage between them, and the presence of genetic isolates and semi-isolates in some extended families and Bedouin tribes. Genetic services have been available in Kuwait for over a decade. During this time it has become clear that Arabs have a high frequency of genetic disorders, and in particular autosomal recessive traits. Their pattern is unique and some disorders are relatively common. Examples are Bardet-Biedl and Meckel syndromes, phenylketonuria, and familial Mediterranean fever. A relatively large number of new syndromes and variants have been delineated in Kuwait's population, many being the result of homozygosity for autosomal recessive genes that occurred because of inbreeding. Some of these syndromes have subsequently been found in other parts of the world, negating the concept of the private syndrome. This paper provides an overview of autosomal recessive disorders among the Arabs in Kuwait from a personal perspective and published studies, and highlights the need for genetic services in Arab countries with the goal of prevention and treatment of genetic disorders.
A 5-year prospective study of 4,934 children of different ethnic groups has demonstrated a 3-fold increase of postneonatal mortality and childhood morbidity in the offspring of consanguineous Pakistani parents. Most of these families contained more than one consanguineous union, resulting in a mean inbreeding coefficient for their children of 0.0686. It is estimated that 60% of the mortality and severe morbidity of this group of children could be eliminated if inbreeding ceased. However consanguinity is much favoured in this minority group, and health education will have to be carefully and sensitively handled.
A newborn with a rare type of lissencephaly is reported, characterized by extreme cerebral and cerebellar hypoplasia. The diagnosis was made by postmortem magnetic resonance imaging, indicating the value of such studies to evaluate neuronal migration disorders in patients in whom autopsy cannot be performed. Two earlier described microlissencephaly syndromes, the "Barth" and "McComb" type, are reviewed.
The cranial magnetic resonance imaging findings in three siblings with nonrhizomelic chondrodysplasia punctata due to isolated dihydroxyacetonephosphate acyltransferase (DHAP-AT) deficiency are reported. Areas of high signal intensity in a patchy distribution on the T2-weighted images were detected in the centrum semiovale in the eldest patient (a 6-year-old girl). The white matter of the second child (a 5-year-old boy) was spared, whereas the youngest sibling (a 2-year-old boy) manifested very severe white matter abnormalities. DHAP-AT catalyzes the first step in the synthesis of plasmalogens, which are major constituents of myelin. Defective plasmalogen synthesis may have contributed to abnormal myelin formation in 2 patients. Because the clinical presentation of the child without detectable defect in myelination was similar to that of his siblings, the neurologic signs observed in isolated DHAP-AT deficiency cannot be attributed solely to the disturbances in the myelin formation.
We report a baby with aprosencephaly, preaxial limb defect and ambiguous genitalia. This combination of abnormalities have been reported previously and constitute the XK aprosencephaly syndrome.
We report a child with multiple congenital abnormalities which include complex central nervous system malformations, dense bones with wide irregular metaphyses, facial dysmorphic features and lethality. We suggest that the combination of abnormalities in the child could represent a new syndrome.
An inbred Arab family with three neonates affected by microlissencephaly syndrome is reported. Brain magnetic resonance imaging in the index case revealed very thin brain mantle with agyria-pachygyria, agenesis of the corpus callosum, and hypoplasia of the brainstem and cerebellum. All three neonates had microcephaly, arthrogryposis multiplex congenita, and micropenis. The presence of three affected newborn infants in a consanguineous family suggests an autosomal-recessive mode of inheritance of this syndrome. The spectrum of microlissencephaly syndrome is reviewed.
We report three neonates, one boy and two girls, born to an inbred Arab family who had cortical dysplasia, probably agyria-pachygyria, and agenesis of the corpus callosum. All had asphyxia, intractable seizures, and increased muscle tone at birth and died in the neonatal period. Congenital microcephaly or dysmorphic features were absent. Cytogenetic abnormality, metabolic disorder, and intrauterine infection were excluded. These cases suggest a new cerebral dysgenesis syndrome with autosomal recessive inheritance.