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Cyclopia (alobar holoprosencephaly) (OMIM% 236100) is a rare and lethal complex human malformation, resulting from incomplete cleavage of prosencephalon into right and left hemispheres occurring between the 18th and the 28th day of gestation. Holoprosencephaly occurs in 1/16,000 live births, and 1/250 during embryogenesis. Approximately 1.05 in 100...
Citations
... Holoprosencephaly is divided into three types, including lobar, semi-lobar, and alobar (cyclopia) holoprosencephaly. Worldwide, cyclopia with proboscis is the rarest and most lethal form of HPE and is incompatible with extrauterine life as was observed in our case [3,[9][10][11]. In cyclopia, the brain does not divide, with a resultant undifferentiated cerebral hemisphere associated with a monoventricles, cranial midline widen the gap to access healthcare. This case report is aimed at increasing awareness of the occurrence of cyclopia and the need for a high level of suspicion in all fetuses with abnormal intracranial sonographic findings such as ventriculomegaly. ...
... abnormalities, and fusion of the thalamus [3,9,10]. Some syndromic sequences that have been associated with cyclopia include Trisomy 13, Pseudo-trisomy 13, Smith-Lemli-Opitz Syndrome, Pallister-Hall Syndrome, and other Aneuploidies [9]. ...
... Some syndromic sequences that have been associated with cyclopia include Trisomy 13, Pseudo-trisomy 13, Smith-Lemli-Opitz Syndrome, Pallister-Hall Syndrome, and other Aneuploidies [9]. Clinically, cyclopia often presents with severe facial defects, usually a single eye field and a proboscis above the eye [10][11][12]. Some non-facial features include polydactyly, ventricular septal defects, renal dysplasia, and omphalocele, which often depicts poor prognosis and most often presents with stillbirth [2,9,10,12]. ...
... Cleft lip is the mildest facial abnormality of holoprosencephaly, and alobar holoprosencephaly (cyclopia) is the most severe form, characterized by undifferentiated holosphere of cerebral parenchyma with a central single ventricle, fused thalami and absence of midline structures like corpus callosum and falx cerebri. [8][9][10][11][12][13] Cardinal facial features of cyclopia may include a single orbit with a median single eye or partially divided eye (synophthalmia), absent nose, a proboscis above the eye, absent philtrum, otocephaly, astomia or microstomia. Extrafacial characteristics can include polydactyly, omphalocele and renal dysplasia. ...
... These obvious features of cyclopia or other forms of holoprosencephaly can be detected by antenatal USG (Ultrasonography) or MRI (Magnetic resonance imaging) if looked carefully. [9][10][11][12][13] In this case, intrauterine facial features were passed undetected. ...
... However, various risk factors implicated include genetic factors and chromosomal anomalies (mostly trisomy D), multiple pregnancies (especially twin pregnancy), previous unexplained miscarriages, maternal diabetes, infections during pregnancy (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus), exposure to UV light and ionic radiation, smoking, alcohol and certain drugs during pregnancy (such as salicylates, amidopyrine, corticosteroids, aspirin, lithium, anticonvulsants, retinoic acid, anticancer agents, cyclopamine [Veratrum californium, found in corn lily or false hellebore]). 1,3,5,[13][14][15][16][17] However, in the presented case, no risk factors could be identified. ...
A rare form of median faciocerebral dysplasia, characterized by a single central orbital fossa with a tubular nose-like appendage above the orbit is known as cyclopian malformation/monster. It is the most severe form of alobar holoprosencephaly. Since most of these cases are sporadic, incompatible with life, and due to the limited literature knowledge, the exact etiology of this condition remains undetermined. However, various risk factors implicated include genetic factors and chromosomal anomalies (mostly trisomy D). Here we present a case of stillborn male cyclopian fetus born to a 34 year old 3rd gravida by caesarean section. There was no history of any drugs or alternative medicine intake (except iron-folic acid, calcium, thyroxin), radiation exposure, or a significant family history or consanguinity. Her only 33-week scan (done at a peripheral center) failed to identify any fetal abnormality. This case is reported because cyclopia is a rare/uncommon developmental anomaly especially with the advancement in antenatal ultrasonography to identify malformed fetuses early in pregnancy.
... 2,3 Cyclopia has been reported to be associated with different risk factors including maternal diabetes, infections and genetic abnormalities. 4,5 The diagnosis of cyclopia is mostly established after 20 weeks of gestation by ultrasonography (USG). 1 To our knowledge, this is the first case of cyclopia reported in Democratic Republic of the Congo (DRC) and especially in eastern rural region of the country. We are presenting a case of synophtalmia term female newborn from a non-consanguineous marriage. ...
... Other facial features are absent philtrum, otocephaly, and astomia or microstomia. 5,10 In this case, at birth, we found to have the typical facial features of cyclopia including a median single orbit with two corneum (synophtalmia), absence of nose, micrognathia and a proboscis above the eye (Figure 1). ...
... Apart from facial features of cyclopia, there are other extra facial features reported and could include polydactyly, renal dysplasia, and omphalocele all of which can be detected by sonography if present and this depends on the underlying cause. 3,5 The presence of extra facial abnormalities carries a very poor prognosis and almost always associated with stillbirth. 1,3,5 Sonography and magnetic resonance imaging (MRI) are the most helpful in the prenatal diagnosis of cyclopia and associated abnormalities; 1,13 however, for this case report, none of the abovementioned investigations was done due to their unavailability and that the anomaly was diagnosed after birth. ...
Synophtalmia or cyclopia is a rare presentation of alobar holoprosencephaly. Cases which have been reported are stillborn or dead in post-delivery period. We are presenting a 3000-g live full-term newborn girl delivered by caesarean section with a well-marked cyclopia, but who died 30 min post-delivery. The case did not present with other abnormalities. The literature showed that genetic disorders are associated with cyclopia. A prenatal anomaly scan can help in the early detection of the condition and timely termination of the pregnancy can be conducted.
... naissances [2]. Elle résulte d'un clivage incomplet du prosencéphale en hémisphère droit et gauche se produisant entre le 18e et les 28e jours de gestation [3]. L'étiopathogénie est mal comprise. ...
... Sur le plan Clinique, il existe une grande variabilité Clinique. En effet diverse tableaux malformatifs ont été rapportés dans la littérature [1,3,6,8]. Sur le plan paraclinique, L'échographie anténatale a un grand intérêt diagnostique. Elle permet de poser le diagnostic de la malformation dès le premier trimestre de la grossesse ce qui est suffisante pour poser l'indication d'une interruption de la grossesse [4,9]. ...
Cyclopia is the most severe form of alobar holoprosencephaly. It is a rare congenital malformation characterized by the fusion of the two orbits and the presence of a single eye in the middle of the forehead, hence its name. It is incompatible with life and presents a heterogeneous clinical picture. Antenatal ultrasound is essential for early diagnosis. However, in developing countries where pregnancies are poorly monitored or not, this malformation is most often discovered in the delivery room. We report a case of cyclopia in a newborn discovered in the delivery room in a context of head-last retention. The objective was to share the experience of our service on this pathology and to show the need for antenatal diagnosis through optimal monitoring of pregnancy in our regions.
... It had a single central facial diamond-shaped eye with 2 pupils and proboscis, representing the nose, above the eye. The other extracranial features like polydactyl, renal dysplasia, and an omphalocele reported in other literatures (Salama 2015) were absent in the index case. Conspicuously, however, there was a one chambered heart and a very short neck. ...
... Cyclopia or alobar holoprosencephaly is a rare congenital disorder characterised by a single eye placed in the median position or a partially divided eye in a single orbit (Salama et al. 2015). Absence of nose and presence of proboscis can also be associated with this disease. ...
Tumor angiogenesis is the most crucial step in the progression of all types of cancers. Preexisted blood vessel vascularizes into new one through sprouting or intussusceptive (splitting) mechanism. This process would facilitate the growth in the size of tumors regulated by VEGF (vascular endothelial growth factor), leading to metastasis, which ultimately increases the severity of cancer. So, it is very important to suppress tumor angiogenesis before the situation gets worse in a cancer patient. A wide variety of in vitro and in vivo models have been used to study the process of tumor angiogenesis and metastasis of cancer. It has helped us to discover new drugs and to find novel therapies for cancer, including anti-angiogenic therapy. Mainly angiogenesis is traditionally modeled in rodents and chick embryo, but of late zebrafish is emerging as the preferred model due its several advantages over the other animals. Zebrafish (Danio rerio) serves as the ideal model to study the various cancers, since it is possible to induce tumor growth or suppression easily, when compared to the other animal models. Also, tumor xenograft model has been studied in zebrafish extensively using many human cancer cell lines. So, in this chapter, we have reviewed some literatures that appreciate zebrafish model to study tumor angiogenesis.KeywordsZebrafishAngiogenesisVEGFTumorXenograftAnti-angiogenic therapy
... Its incidence is 1 in 1,00,000 newborns out of which 50% are stillborn and rest survive only for few hours 2,3 . There is preponderance of female babies born with cyclopia 4 . It is a life threatening severe faciocerebral development deformity. ...
Cyclopia is the rare manifestation of most severe degree of alobar holoprosencephaly1. Its most cardinal feature is presence of single eye or partially divided eye in a single socket at mid face with varying degrees of fusion of globes. The teratogenic factors leading to this anomaly include genetics, drugs, infection, radiation. Very few reports have documented this anomaly in newborn. Hence we present a case of stillborn baby of cyclopia with synophthalmia to a 27 year old woman who presented in second stage of labour with USG showing placenta previa. Early prenatal diagnosis, genetic study and proper management of this anomaly should be emphasized for better outcome in future. Key words: cyclopia; holoprosencephaly; teratogenic; synophthalmia; prenatal diagnosis.
... In 2015, the live birth of a newborn with cyclopia was reported in Jordan. The newborn died in hospital within 5 h after birth [14]. Most studies have shown that a baby born with cyclopia syndrome has a maximum lifespan of 10-12 h [1,3,13], but despite the anomaly of the respiratory system, our case survived 13 h, which was the longest survival time of a newborn with cyclopia syndrome. ...
Introduction and importance
Cyclopia is a rare congenital disorder characterized by facial abnormalities. In this condition, the orbits of the eye are not properly divided into two cavities so that they can be seen either as a single eye field or two bilateral fields that are very close to each other. This syndrome affects the embryos that are either aborted or stillborn upon delivery or, at best, die shortly after birth.
Case presentation
This case report is of a 37-week- and 5-day-old female fetus with a birth weight of 2300 g, a height of 43 cm, and a head circumference of 31 cm. She was born to a 44-year-old mother through normal vaginal delivery at Mahzad Hospital, Urmia, Iran. In the physical examination, an eye and a 4-cm proboscis were seen in the middle of the forehead. The newborn also had no nose, and his outer ears were normal. No cleft lip or cleft palate was observed. Unfortunately, the newborn expired 13 h after birth.
Clinical discussion
Cyclopia leads to a stillbirth since the brain and other parts of the body do not grow normally in fetuses with this disorder. Moreover, it can be diagnosed using ultrasonography while the fetus is growing inside the uterus.
Conclusion
Early diagnosis during pregnancy using diagnostic methods and proper management of this abnormality should be emphasized to prevent further harm to the newborn and the mother with this syndrome. Moreover, many of these newborns should be offered early neonatal palliative care.
... Imaging, especially prenatal ultrasound is the routinely diagnosis tool (Bangma & Galjaard, 2011), but fetal magnetic resonance imaging (MRI) is the gold standard in the diagnosis of HPE because of its high resolution on soft tissue (cortical, white matter, and other deep structures) and predicts the severity and morbi-mortality of HPE (Hahn & Barnes, 2010;Kousa et al., 2018;Raman & Mukunda, 2014). As we know that HPE results from a lack of division of prosencephalon around 4-5 weeks of pregnancy, imaging diagnosis of HPE is age dependent (Orioli & Castilla, 2010;Salama et al., 2015). Practically, ultrasound during the first and the second trimester prenatal visit is the crucial for the diagnosis of HPE (Bangma & Galjaard, 2011). ...
... Termination of such pregnancy is allowed in DRC law in case that a nonviable fetal malformation (e.g., anencephaly or HPE) is found in early ultrasound examination; unfortunately, the remaining public health issue is the lack of routine prenatal visit and ultrasound financial accessibility in DRC and other low-middle income countries (Orioli & Castilla, 2010). In a study conducted in Jordan, termination was not done because not legitimated (Salama et al., 2015). The etiology of HPE remains unknown, but it seems a multifactorial disease caused by both environmental and genetic factors (Addissie et al., 2021;Dubourg et al., 2018;Orioli & Castilla, 2010;Winter, Kennedy, & Woodward, 2015). ...
... The two regions of DRC seem to be linked to mining activities and ionizing irradiation thus may join them by hypothesizing that this exposure to mining and radiation may damage the genetic materials and lead to some epigenetics alteration of spermatozoids conducting to such malformations (Kayembe-Kitenge et al., 2019). The two cases were born spontaneously and with the cephalic presentation, while in other case reports, fetal bradycardia has been the indication for caesarian section (Ionescu et al., 2018;Salama et al., 2015). Their birth weights were superior to 2,500 g as reported by Salama et al. case with 2,900 g (Salama et al., 2015). ...
Background: Recent case reports described three cases of holoprosencephaly (HPE) in the area with high mining-related pollution of the southern region of the Democratic Republic of the Congo (DRC). We reported two male neonates with clinically diagnosed HPE in the localities of Fizi and Kitutu, two mineral areas in the Eastern region of the same country (DRC), where artisanal surface mining is predominant with high exposure to radiation and heavy metals from mining.
Cases' presentations: Two newborns from adult and multigravida mothers without pregnancy complication. The birth weights were 3,200 g and 2,500 g, respectively, and the malformations noticed were essentially the single median eye, the absent nose, polydactyly for one case, and proboscis for the other case. They both died a few minutes later after birth.
Conclusion: The etiologic factors of HPE remain unknown but seem to be multifactorial from both genetic and environmental factors. We hypothesize under reserve for these two cases that mining and radiation expositions were likely potential environmental associated factors to the occurrence of these malformations.
K E Y W O R D S: Birth defect, congenital malformation, cyclopia, the Democratic Republic of the Congo, holoprosencephaly, mining-related pollution.
... The ears can be partially or totally absent or malpositioned. In our report, the left ear was misplaced closer to the mouth [6,11,12]. Worthy of note, most of the cases are stillborn, but there are full-term infants that have survived for few minutes to hours. The coexistence of extrafacial abnormalities such as polydactyle, omphalocele, genital, renal, and visceral abnormalities almost always associates with a stillbirth. ...
The most extreme form of holoprosencephaly (HPE)is cyclopia and appears with a single characteristic midline diamond-shaped orbital structure and various facial, brain, and extrafacial features. We aimed to report a case of a cyclopic fetus diagnosed at the 22 weeks of the gestational age and further we reviewed the recent literature in order to highlight the etiopathogenesis and set goals for approaching such future pregnancies. Following the first-trimester assessment, in a 27-year-old pregnant woman, who underwent in vitro fertilization, the pregnancy was associated with a low risk for aneuploidies and a high risk for pre-eclampsia. On the anomaly scan, due to severe fetal brain maldevelopment and microcephale, HPE was suspected. Furthermore, three-dimensional ultrasound confirmed a common orbit in the midline of the face. Although the parents did not opt for amniocentesis and further postnatal management, parental karyotyping test did not detect any pathology. The pregnancy was terminated and the macroscopic examination of the aborted specimen revealed cyclopia, synophalmia, fussed eyelids with a proboscis on the upper midline of the face, and a malpositioned left ear. To conclude, cyclopia is not widely manifested, and different cyclo-pian disorders could still occur. Although this rare congenital abnormality is incompatible with life, the awareness of the spectrum of sonographic features and the appropriate genetic counseling can determine the outcome of current and forthcoming pregnancies.
