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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe two brothers with a unique pattern of malformations that includes coloboma (iris, optic nerve), high forehead, severe retrognathia, mental retardation, and agenesis of the corpus callosum (ACC). Both boys have low-set cupped ears with sensorineural hearing loss, normal phallus, pectus excavatum, scoliosis, and short stature. One brother had choanal atresia and cardiac defects consisting of ventricular septal defect (VSD) and patent ductus arteriosus (PDA) which resolved spontaneously. Differential diagnosis between a number of clinical entities was considered, however, because ACC and the distinctive facial features were reminiscent of FG syndrome, DNA was analyzed for markers linked to the FGS1 locus at Xq13-q21. Notably, the brothers were concordant for markers spanning this presumed FG region, and in both we have identified adjacent alterations (-57delT and T-55A) in the Alpha 4 gene located within this interval. Alpha 4 is a regulatory subunit of the major cellular phosphatase, PP2A, that has recently been shown to interact with MID1, the product of the gene mutated in X-linked Opitz GBBB syndrome. The double nucleotide change identified in this family was not observed in 410 control chromosomes, suggesting that it may be a pathogenetic change. Altered expression of Alpha 4, through either a change in translational efficiency, mRNA stability or splicing, could explain the clinical phenotype in these boys and the phenotypic overlap with Opitz GBBB syndrome.
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PMID:A new X-linked syndrome with agenesis of the corpus callosum, mental retardation, coloboma, micrognathia, and a mutation in the Alpha 4 gene at Xq13. 1455 45

Knowing the origin of cytogenetic abnormalities detected in individuals with mental retardation and dysmorphic features is essential to genetic counselling of affected families. To illustrate this, we report on six families with transmitted cytogenetic abnormalities and discuss the genotype-phenotype correlations, including the possibility of the abnormalities being normal genomic variants. The abnormalities were detected using metaphase HR-CGH; their size was estimated to range from 1.6 to 7.5 Mb using tiling path array-CGH and real-time PCR. The abnormalities were transmitted through two to four generations and included interstitial deletions of 1p31.3-p32.1, 2q13, 10q11.21-q11.23, and 13q31.1; a duplication of 1p34.1-p34.2; and in one family both a deletion of 18q21.1 and a duplication of 4q35.1-q35.2. The probands were mentally retarded and had nonspecific dysmorphic features except for one patient with the Bohring-Opitz syndrome. We considered the abnormalities in two families to be clinically significant: In one family, the proband's brain abnormality was comparable to previously reported abnormalities in individuals with a similar duplication of 1p31-p32. Congenital heart disease was previously mapped to the chromosomal region of 18q that was affected in the proband of another family. The carrier parents in both families had mild clinical features. In two families the abnormalities were considered as coincidental findings, and in two further families the abnormalities were insufficient to explain the phenotypes of the probands but possibly were related to a milder phenotype in other family members. These cases illustrate the need for careful assessment of the extended family in order to interpret the phenotypic consequences of abnormalities identified using array-CGH.
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PMID:Transmitted cytogenetic abnormalities in patients with mental retardation: pathogenic or normal variants? 1753 65

Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS.
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PMID:Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome. 1807 89

Opitz syndrome is a rare autosomal recessive disorder of cholesterol metabolism associated with mental retardation and multiple congenital malformations. It is also uncommonly associated with congenital glaucoma. We describe the orbital findings on CT in this rare case of a patient with Opitz syndrome who presented with congenital glaucoma, with a review of the literature. The CT findings of congenital glaucoma, which have not been described before in the literature, are also discussed. It is important for the radiologist to be aware of this rare association. It is also important to be aware of the findings of congenital glaucoma on CT because patients with Opitz syndrome and other syndromes associated with learning difficulties may not present with typical clinical features of glaucoma. A high index of suspicion will lead to a correct diagnosis and earlier intervention.
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PMID:Imaging findings of congenital glaucoma in Opitz syndrome. 1831 Feb 33

The study of de novo point mutations (new germline mutations arising from the gametes of the parents) remained largely static until the arrival of next-generation sequencing technologies, which made both whole-exome sequencing (WES) and whole-genome sequencing (WGS) feasible in practical terms. Single nucleotide polymorphism genotyping arrays have been used to identify de novo copy-number variants in a number of common neurodevelopmental conditions such as schizophrenia and autism. By contrast, as point mutations and microlesions occurring de novo are refractory to analysis by these microarray-based methods, little was known about either their frequency or impact upon neurodevelopmental disease, until the advent of WES. De novo point mutations have recently been implicated in schizophrenia, autism and mental retardation through the WES of case-parent trios. Taken together, these findings strengthen the hypothesis that the occurrence of de novo mutations could account for the high prevalence of such diseases that are associated with a marked reduction in fecundity. De novo point mutations are also known to be responsible for many sporadic cases of rare dominant mendelian disorders such as Kabuki syndrome, Schinzel-Giedion syndrome and Bohring-Opitz syndrome. These disorders share a common feature in that they are all characterized by intellectual disability. In summary, recent WES studies of neurodevelopmental and neuropsychiatric disease have provided new insights into the role of de novo mutations in these disorders. Our knowledge of de novo mutations is likely to be further accelerated by WGS. However, the collection of case-parent trios will be a prerequisite for such studies. This review aims to discuss recent developments in the study of de novo mutations made possible by technological advances in DNA sequencing.
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PMID:A new paradigm emerges from the study of de novo mutations in the context of neurodevelopmental disease. 2264 Nov 81


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