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The investigated markers and their locations on the X and Y chromosomes (a) and the allele patterns of the polymorphic markers (b). QF-PCR analysis of X chromosome markers confirmed chromosomal constitutions of PBLs and skin FBs. Tetrasomy X/trisomy X mosaicism in PBLs was evidenced by trisomic diallelic pattern (2:1) for X22 (Xq28/ Yqter) and DXYS267 (Xq21.31/Yp11.31), tetrasomic diallelic pattern (3:1) for DXYS218 (Xp22.32/Yp11.3), and tetrasomic triallelic pattern
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Tetrasomy X associated with premature ovarian failure has been described in a few patients, and the parental origin of the extra X chromosomes has not been investigated so far in this group. A 15-year-old girl with mental retardation and minor physical anomalies showed secondary amenorrhea, high gonadotropin levels, and osteoporosis. M...
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Context 1
... determine the origin of the extra X chromosomes, we studied on the poly- morphic markers on the X chromosome (X22, DXYS218, DXYS267, and HPRT) in the patient and her parents by the quantitative fluorescent polymerase chain reaction (QF-PCR) method. The investigated polymorphic markers and their lo- cations on the X and Y chromosomes are shown in Fig. 1a. QF-PCR analysis revealed tetrasomic diallelic and triallelic patterns in skin fibroblasts, and trisomic and tetrasomic diallelic patterns in peripheral blood lymphocytes. By analyz- ing inherited alleles of the polymorphic markers, we conclud- ed that the extra X chromosomes were maternal in origin (Fig. ...
Context 2
... on the X and Y chromosomes are shown in Fig. 1a. QF-PCR analysis revealed tetrasomic diallelic and triallelic patterns in skin fibroblasts, and trisomic and tetrasomic diallelic patterns in peripheral blood lymphocytes. By analyz- ing inherited alleles of the polymorphic markers, we conclud- ed that the extra X chromosomes were maternal in origin (Fig. ...
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Citations
... In individuals with tetrasomy X, non-specific dysmorphic signs, skeletal and connective tissue abnormalities are manifested. There are frequent cases of epicanthus, hypertelorism, flattened nose, up slanting palpebral fissures, irregular teeth, microgenia, clinodactyly, radioulnar synostosis, and joint hyperlaxity [2,[14][15][16]20,26] . In some patients, vision disorders, pathologies of the cardiovascular and renal systems, among others, have been described [2,17,27,28] . ...
... Mechanisms of formation of tetrasomy X have been studied only in a part of the cases described in the literature [11,15,35] . These studies identified double successive maternal nondisjunction at meiosis as the most common mechanism, although more rarely, X tetrasomy can be the result of meiotic errors in both parents or errors at early mitotic division and also as a result of the maternal trisomy X [11,15,35,36] . ...
... Mechanisms of formation of tetrasomy X have been studied only in a part of the cases described in the literature [11,15,35] . These studies identified double successive maternal nondisjunction at meiosis as the most common mechanism, although more rarely, X tetrasomy can be the result of meiotic errors in both parents or errors at early mitotic division and also as a result of the maternal trisomy X [11,15,35,36] . Scant literature data on tetrasomy X does not allow determining the role of maternal age in these cases [13,37] . ...
Tetrasomy X (48,XXXX) is an extremely rare condition in women and is characterized by wide phenotypic variability without specific pathognomonic characteristics. Very few cases of tetrasomy X with premature ovarian insufficiency have been described in the literature. We identified the 48,XXXX karyotype in a 17-year-old adolescent girl with tall stature (179 cm), who was referred to us for secondary amenorrhea. Premature ovarian insufficiency was diagnosed based on the results of the conducted examination, which revealed elevated levels of gonadotropins and small ovaries without follicles. The patient had psychomotor retardation (IQ of 59), a speech defect, minor physical anomalies (microgenia, high-arched palate, bilateral clinodactyly of the 5th finger of the upper extremities). Mild osteopenia, insulin resistance, and a small, asymptomatic Rathke's cleft cyst in the adenohypophysis was also detected. Karyotype 48, XXXX was identified by G-banding in the culture of peripheral blood lymphocytes. For the diagnosis of tetrasomy X in patients with premature ovarian insufficiency and psychomotor retardation, karyotyping is advisable despite the scarcity of minor physical anomalies. Timely initiation of estrogen replacement therapy from early puberty in such patients is important, as it ensures completion of pubertal development, control of longitudinal growth and prevention of negative long-term consequences of estrogen deficiency, including osteoporosis.
... The mechanism of the disease may be that the dose of a speci ic X gene product is required for correct ovarian maintenance, or it may be that the oocytes cannot degrade due to the lack of X chromosome homologous partners and normal meiosis [11]. Individuals with trisomy X (47, XXX) usually do not experience reduced fertility, but many case studies report that POI is associated with this karyotype [12,13]. The prevalence of trisomy X in the POI population is estimated to be between 1% to 4% [14]. ...
Premature ovarian insufficiency (POI) is a rare disease, especially in children and adolescents. It was previously called premature ovarian failure (POF). It can be manifested as delayed puberty, primary or secondary amenorrhea that occurred before the age of 40 years with no less than two abnormal serum sex hormones (low estrogen and high gonadotropin). It is reported that the incidence rate is 1% at the age of 40 years and 0.01% at the age of 20 years. Although the disease usually occurs in middle-aged and elderly women, clinical practice in recent years has shown that it has also been found in adolescents and even children. It is generally believed that the etiology of POI includes genetic factors, immune factors, and iatrogenic factors. So far, several genetic mutations that may cause POI have been found clinically, but the etiology of 90% of POI is still unknown. In recent years, the incidence of POI in children and adolescents has increased, and there are more urgent requirements for its early diagnosis, treatment, and clinical management. Based on this, this article will mainly review the research progress of the etiology, treatment, and clinical management of POI in children and adolescents.
... Physical abnormalities in 48, XXXX girls include hypertelorism, epicanthical folds, eye anomalies including myopia and iridoschisis, dental abnormalities, and skeletal abnormalities including clinodactyly and radioulnar synostosis [Di Cagno and Franceschini, 1968;Sokolowski et al., 1969;Berkeley and Faed, 1970;Peña et al., 1974]. External genitalia is usually normal in 48, XXXX girls, but several cases have reported irregular menarche, absent ovaries and premature ovarian failure [Collen et al., 1980;Kara et al., 2013]. There has been one report of a successful pregnancy in a 27-year-old 48, XXXX woman who gave birth to a healthy child with normal cytogenetics [Blackston et al., 1994]. ...
49,XXXXY is the rarest X and Y chromosomal variation and is frequently characterized by expressive and receptive language dysfunction, low muscle tonus, and intellectual deficits. Due to the low incidence of this disorder, comprehensive studies analyzing the specific aspects of the speech and language phenotype in these boys have been uncommon. This is the first in‐depth investigation of the speech and language profiles in a large cohort of boys with 49,XXXXY. Based on the clinical judgment of speech and language pathologists, there was an increased incidence (91.8%) of Childhood Apraxia of Speech (CAS), which has not been previously described in this disorder. In preschool boys, some significant differences were demonstrated between boys who received early hormonal treatment (n = 16) and untreated boys (n = 4) on the language scales (p = .047) on the Bayley Scales of Infants and Toddlers, as well as significant differences between treated (n = 13) and untreated boys (n = 8) on the Expressive One Word Picture Vocabulary Test (p = .008). No significant differences between treatment groups were found in school age children, however, treated groups demonstrated less discrepancies between expressive and receptive language. More research and larger samples are needed to determine the extent of the impact of testosterone treatment on boys with 49,XXXXY. This study identifies CAS as a potential explanation for the significant expressive language dysfunction and subsequent behavioral dysfunction. These findings may assist in facilitating more targeted treatment and improved outcomes for boys with 49,XXXXY.
... for her limb pain including arthralgia and meralgia. Although some cases with polysomy X have been reported, most of them without SLE did not complain of pain including arthralgia[14][16][17]. Recent evidence has shown that autoan- tibodies against adrenergic and cholinergic receptors play an important role in the appearance of both orthostatic dysregulation and CRPS[18][19]. ...
... It has been reported that with an increasing number of X chromosomes, the frequency of premature ovarian insufficiency increases, and the age at presentation decreases, possibly due to earlier depletion of ovarian follicles. 10 Therefore, it has been suggested that patients with tetrasomy X should be screened for ovarian insufficiency during early adolescence, as hormone replacement therapy may be required for the development of secondary sex characteristics and for prevention of eventual osteoporosis. 10 However, some patients with 48, XXXX may have normal ovarian function. ...
... 10 Therefore, it has been suggested that patients with tetrasomy X should be screened for ovarian insufficiency during early adolescence, as hormone replacement therapy may be required for the development of secondary sex characteristics and for prevention of eventual osteoporosis. 10 However, some patients with 48, XXXX may have normal ovarian function. 11 RCC has rarely been reported in children and adolescents 12 and may not be discovered clinically until late adulthood. ...
Background:
Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella.
Methods/results:
The patient was diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple endocrine stimulation tests revealed RCC and combined pituitary hormone deficiency (growth hormone deficiency, secondary adrenal insufficiency and central hypothyroidism) likely due to RCC.
Conclusion:
We report the first case in the literature of a girl with 48, XXXX and combined pituitary hormone deficiency due to Rathke's cyst.
... Physical abnormalities in 48, XXXX girls include hypertelorism, epicanthical folds, eye anomalies including myopia and iridoschisis , dental abnormalities, and skeletal abnormalities including clinodactyly and radioulnar synostosis [Di Cagno and Franceschini , 1968; Sokolowski et al., 1969; Berkeley and Faed, 1970; Pe~ na et al., 1974]. External genitalia is usually normal in 48, XXXX girls, but several cases have reported irregular menarche, absent ovaries and premature ovarian failure [Collen et al., 1980; Kara et al., 2013]. There has been one report of a successful pregnancy in a 27-year-old 48, XXXX woman who gave birth to a healthy child with normal cytogenetics [Blackston et al., 1994]. ...
Fourty eight, XXXX is a rare chromosomal aneuploidy associated with neurocognitive deficits, speech and language disorders and executive dysfunction but the scarcity and variability of reported cases limit our understanding of the 48, XXXX phenotype. To our knowledge, this is the first study to report on the neurodevelopmental profile of three young females with 48, XXXX. Patient 1 (age = 11.0), Patient 2 (age = 10.9), and Patient 3 (age = 6.4) were evaluated using comprehensive neurodevelopmental assessments. Parent questionnaires were completed to assess behavioral and psychosocial domains including executive function, ADHD and anxiety. Nonverbal intelligence quotients were 56, 80, and 91 for Patients 1, 2, and 3, respectively. There were significantly impaired visual motor capacities in graphomotor and perceptual domains below the 5th centile in Patients 1 and 2, and mildly impaired visual perception skills in Patient 3. All three patients had Childhood Apraxia of Speech (CAS) but of varying severity and similar executive dysfunction, externalizing problems and social difficulties. Familial learning disabilities (FLD) in Patient 1 and the co-occurrence of ADHD in Patient's 1 and 2 may contribute to their more impaired cognitive performances relative to Patient 3 who is the second reported case of 48, XXXX to have normal intellect. These distinct and overlapping characteristics expand the phenotypic profile of 48, XXXX and may be used in the counseling of families and treatment of children with 48, XXXX. © 2015 Wiley Periodicals, Inc.
© 2015 Wiley Periodicals, Inc.
... Physical abnormalities in 48, XXXX girls include hypertelorism, epicanthical folds, eye anomalies including myopia and iridoschisis , dental abnormalities, and skeletal abnormalities including clinodactyly and radioulnar synostosis [Di Cagno and Franceschini, 1968; Sokolowski et al., 1969; Berkeley and Faed, 1970; Pe~ na et al., 1974]. External genitalia is usually normal in 48, XXXX girls, but several cases have reported irregular menarche, absent ovaries and premature ovarian failure [Collen et al., 1980; Kara et al., 2013]. There has been one report of a successful pregnancy in a 27-year-old 48, XXXX woman who gave birth to a healthy child with normal cytogenetics [Blackston et al., 1994]. ...
We report on a mildly abnormal 5-year-old girl with seizures, psychomotor retardation, and areas of hyperpigmentation who had a supernumerary marker chromosome in fibroblasts which was identified as an i(5p). To our knowledge, this is the first reported case of tetrasomy 5p. She shares in common some, but not all, manifestations of the dup (5p) syndrome. Cytogenetic analysis of relatives showed that the phenotypically apparently normal mother, maternal grandmother, and a brother of the proband also had a marker chromosome in their lymphocytes which was unrelated to the i(5p).
Patients with complex rare genetic syndromes (CRGS) have combined medical problems affecting multiple organ systems. Pediatric multidisciplinary (MD) care has improved life expectancy, however, transfer to internal medicine is hindered by the lack of adequate MD care for adults. We have launched an MD outpatient clinic providing syndrome-specific care for adults with CRGS, which, to our knowledge, is the first one worldwide in the field of internal medicine. Between 2015 and 2020, we have treated 720 adults with over 60 syndromes. Eighty-nine percent of the syndromes were associated with endocrine problems. We describe case series of missed diagnoses and patients who had undergone extensive diagnostic testing for symptoms that could actually be explained by their syndrome. Based on our experiences and review of the literature, we provide an algorithm for the clinical approach of health problems in CRGS adults. We conclude that missed diagnoses and needless invasive tests seem common in CRGS adults. Due to the increased life expectancy, an increasing number of patients with CRGS will transfer to adult endocrinology. Internist-endocrinologists (in training) should be aware of their special needs and medical pitfalls of CRGS will help prevent the burden of unnecessary diagnostics and under- and overtreatment.
Premature ovarian failure (POF) is a heterogeneous condition affecting girls and women. We detected a previously healthy 18-year-old adolescent girl, presented with amenorrhea over six months, as well as circulating levels of estradiol lower decreased and follicle-stimulating hormone (FSH) increased. She was 138 cm tall. Results of laboratory tests and/or ultrasound investigations showed 46, X, i(X)(q10) karyotype and Hashimoto’s disease. This case suggests that pubertal onset and progression, as well as karyotype analysis, should be evaluated in girls with Hashimoto’s disease and short stature.
Methyl-CpG-binding protein 2 gene (MECP2; OMIM 300005) is located at chromosome Xq28. Mutations of the gene including point mutation, duplication and deletion can lead to severe neurodevelopmental disorders. The disease caused by duplication of the entire MECP2 gene, named as MECP2 duplication syndrome, is mostly seen in males. The clinical manifestation of this syndrome include mental retardation, hypotonia, poor speech development, recurrent infection, progressive spasticity, epilepsy, autism or autistic features with or without midface hypoplasia. Most patients have inherited the duplication from their unaffected mothers, with only a few cases having de novo mutation. Females with duplicated MECP2 gene are typically asymptomatic because of a skewed X chromosome inactivation (XCI) pattern. Proposed mechanisms of this genomic rearrangement include fork stalling and template switching (FoSTeS) and microhomology mediated break-induced replication (MMBIR). Since no effective treatment is available for this disease, proper genetic counseling and prenatal diagnosis for the high risk families are crucial.
