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

Acrocallosal syndrome is an autosomal recessive form of polysyndactyly associated with mental retardation and agenesis of the corpus callosum. There have been suggestions that it is allelic to the Greig cephalopolysyndactyly syndrome. Linkage analysis, using flanking markers, shows this suggestion is unlikely to be correct.
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PMID:The acrocallosal syndrome and Greig syndrome are not allelic disorders. 140 93

We report on a 53-year-old woman and her 20-year-old son who both presented with polysndactyly, without other external malformations or mental retardation. MRI imaging revealed, as an incidental finding, asymptomatic hypothalamic hamartomas in both patients. The siblings of both mother and son are unaffected. This family may represent an autosomal dominant variant of Pallister-Hall syndrome.
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PMID:Polysyndactyly and asymptomatic hypothalamic hamartoma in mother and son: a variant of Pallister-Hall syndrome. 859 73

Greig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, frameshift, translocation, and gross deletion mutations. FISH and STRP analyses were applied to 34 patients with characteristics of GCPS. Deletions were identified in 11 patients and the extent of their deletion was determined. Nine patients with deletions had mental retardation (MR) or developmental delay (DD) and were classified as severe GCPS. These severe GCPS patients have manifestations that overlap with the acrocallosal syndrome (ACLS). The deletion breakpoints were analyzed in six patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. We conclude that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and we hypothesize that this severe GCPS phenotype is caused by deletion of contiguous genes.
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PMID:Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. 1460 43

Pallister-Hall syndrome (PHS, MIM #146510) is characterized by central and postaxial polydactyly, hypothalamic hamartoma (HH), bifid epiglottis, imperforate anus, renal abnormalities, and pulmonary segmentation anomalies. It is inherited in an autosomal dominant pattern. Here, we describe a family with two affected children manifesting severe PHS with mental retardation, behavioral problems, and intractable seizures. Both parents are healthy, with normal intelligence, and have no malformations on physical, laryngoscopic, and cranial MRI exam. The atypical presentation of these children and the absence of parental manifestations suggested an autosomal recessive mode of inheritance or gonadal mosaicism. Sequencing of GLI3 revealed a two nucleotide deletion in exon 15 (c.3385_3386delTT) predicting a frameshift and premature stop at codon 1129 (p.F1129X) in the children while both parents have wild type alleles. Genotyping with GLI3 intragenic markers revealed that both children inherited the abnormal allele from their mother thus supporting gonadal mosaicism as the underlying mechanism of inheritance (paternity was confirmed). This is the first reported case of gonadal mosaicism in PHS. The severe CNS manifestations of these children are reminiscent of children with non-syndromic HH who often have progressive mental retardation with behavioral problems and intractable seizures. We conclude that the phenotypic spectrum of PHS can include severe CNS manifestations and that recurrence risks for PHS should include a proviso for gonadal mosaicism, though the frequency cannot be calculated from a single case report. Published 2003 Wiley-Liss, Inc.
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PMID:Gonadal mosaicism in severe Pallister-Hall syndrome. 1470 4

The authors report the case of a 12-year-old girl with Pallister-Hall syndrome, long-standing refractory, symptomatic epilepsy, mental retardation, and panhypopituitarism in whom two rare, deep midline lesions were detected. She underwent successful transsphenoidal resection of the Rathke cleft cyst and transcallosal resection of the hypothalamic hamartoma within a 4-day period without complications. Neuropathological studies confirmed the neuroimaging diagnoses for the two lesions. The patient has been seizure free for 6 months postoperatively.
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PMID:Successful resection of a hypothalamic hamartoma and a Rathke cleft cyst. Case report. 1620 38

Complex chromosome rearrangements (CCRs) are rare structural abnormalities that involve at least two chromosomes and more than two breakpoints and are often associated with developmental delay, mental retardation, and congenital anomalies. We report on a de novo, apparently balanced translocation t(1;5;7)(p32.1;q14.3;p21.3) involving three chromosomes in a 7-year-old boy with severe psychomotor retardation, neonatal muscular hypertonia, congenital heart defect, polysyndactyly of hands and feet, and dysmorphic features resembling Greig cephalopolysyndactyly syndrome. Analysis of the chromosome breakpoints using fluorescence in situ hybridization (FISH) with locus-specific BAC clones and long-range PCR products did not identify chromosome imbalance at any of the interrogated regions. High-resolution comparative genomic hybridization (HR-CGH) and array CGH (aCGH) revealed two additional cryptic de novo deletions, del(1)(p31.1p31.1) and del(7)(p14.1p14.1), respectively, that are not associated with the translocation breakpoints. FISH and polymorphic marker analyses showed that the deletion on derivative chromosome 1 is between 4.2 and 6.1 Mb, and the deletion on derivative chromosome 7 is approximately 5.1 Mb, and that both are paternal in origin. The deletion on chromosome 7p encompasses the GLI3 gene that is causative for the Greig cephalopolysyndactyly, Pallister-Hall and some cases of Acrocallosal syndromes. We discuss the potential mechanisms of formation of the described CCR.
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PMID:Complex balanced translocation t(1;5;7)(p32.1;q14.3;p21.3) and two microdeletions del(1)(p31.1p31.1) and del(7)(p14.1p14.1) in a patient with features of Greig cephalopolysyndactyly and mental retardation. 1793 35

Greig cephalopolysyndactyly syndrome (GCPS) is a rare multiple congenital anomaly syndrome that is inherited in an autosomal dominant pattern and is caused by haploinsufficiency of the GLI3 gene. The syndrome typically includes preaxial or mixed pre- and postaxial polydactyly and cutaneous syndactyly, ocular hypertelorism, and macrocephaly in its typical forms, but sometimes includes hydrocephalus, seizures, mental retardation, and developmental delay in more severe cases. Patients with milder forms of GCPS can have subtle craniofacial dysmorphic features that are difficult to distinguish from normal variation. This article presents the spectrum of dysmorphic findings in GCPS highlighting some of its key presenting features to familiarize clinicians with the variable expressivity of the condition.
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PMID:The clinical atlas of Greig cephalopolysyndactyly syndrome. 1824 Oct 58

Maturity-onset diabetes of the young type 2 (MODY2) is a form of monogenic diabetes, characterized by mild fasting hyperglycemia. MODY2 is caused by heterozygous mutations in the GCK gene that encodes the glucokinase enzyme. We describe the clinical features and the underlying genetic defect of MODY2 in a patient with atypical Greig cephalopolysyndactyly syndrome (GCPS). The patient presented with the limb formation and the craniofacial developmental abnormalities typical to GCPS, in addition to mental retardation and epilepsy (assigned as atypical syndrome). Fasting hyperglycemia in the diabetic range, impaired glucose tolerance, and lack of diabetes autoantibodies were compatible with MODY2. In order to delineate the genetic aberrations relevant both to MODY2 and Greig syndrome in this patient, we performed cytogenetic analysis, real-time PCR of the GCK gene, and comparative genomic hybridization (CGH) array. Cytogenetic study has shown a microscopic detectable deletion in the 7p13-15 chromosomal region. Real-time PCR demonstrated a deletion of the GCK gene in the patient but not her parents, and CGH array revealed a deleted region of approximately 12 Mb in the 7p13-15 region. This deleted region included GLI3 and GCK genes (where heterozygous mutations cause GCPS and MODY2, respectively), and many other contiguous genes. Our patient manifests a unique form of MODY2, where GCK gene deletion is part of a large deleted segment in the 7p13-15 chromosomal region.
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PMID:MODY type 2 in Greig cephalopolysyndactyly syndrome (GCPS) as part of a contiguous gene deletion syndrome. 2204 88