Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here a case of a 20-year-old woman with facioscapulohumeral muscular dystrophy (FSHD). In this patient, the involvement of facial muscle had been present since early childhood, but obscured due to the complication of profound mental retardation. Epilepsy emerged at eight years of age. Symmetrical limb muscle weakness appeared at 15 years of age, which progressed such that she was wheelchair-bound at 18 years of age. An elevated serum creatine kinase, predominant involvement of hamstrings, scapular and abdominal muscles, as well as an impaired stapedial reflex at high tune, were compatible with the clinical features of FSHD. The diagnosis of 4q35-FSHD was confirmed by detection of a 10kb EcoRI fragment with a p13E-11 probe on a Southern blot. The intellectual disability in this patient was the most severe of all FSHD patients reported to date and has hindered a correct diagnosis. This entity should be included in the differential diagnoses for patients with muscular symptoms and accompanying mental retardation.
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PMID:Facioscapulohumeral muscular dystrophy with severe mental retardation and epilepsy. 1701 May 49

In a systematic sequencing screen of the coding exons of the X chromosome in 250 families with X-linked mental retardation (XLMR), we identified two nonsense mutations and one consensus splice-site mutation in the AP1S2 gene on Xp22 in three families. Affected individuals in these families showed mild-to-profound mental retardation. Other features included hypotonia early in life and delay in walking. AP1S2 encodes an adaptin protein that constitutes part of the adaptor protein complex found at the cytoplasmic face of coated vesicles located at the Golgi complex. The complex mediates the recruitment of clathrin to the vesicle membrane. Aberrant endocytic processing through disruption of adaptor protein complexes is likely to result from the AP1S2 mutations identified in the three XLMR-affected families, and such defects may plausibly cause abnormal synaptic development and function. AP1S2 is the first reported XLMR gene that encodes a protein directly involved in the assembly of endocytic vesicles.
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PMID:Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation. 1718 71

Norrie disease (ND) is a rare X-linked recessive disorder characterized by congenital blindness and in some cases, mental retardation and deafness. Other neurological complications, particularly epilepsy, are rare. We report on a novel mutation identified in a patient with ND and profound mental retardation. The patient was diagnosed at the age of 6 months due to congenital blindness. At the age of 8 months he developed infantile spasms, which were diagnosed at 11 months as his EEG demonstrated hypsarrhythmia. Mutation analysis of the ND gene (NDP) of the affected child and his mother revealed a novel missense mutation at position c.134T > A resulting in amino acid change at codon V45E. To the best of our knowledge, such severe neurological involvement has not been previously reported in ND patients. The severity of the phenotype may suggest the functional importance of this site of the NDP gene.
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PMID:A novel missense mutation in the NDP gene in a child with Norrie disease and severe neurological involvement including infantile spasms. 1733 93

Studies of human chromosomal aberrations and knockout (KO) mice have suggested SATB2 as a candidate gene for a human malformation syndrome of craniofacial patterning and brain development. Of 59 unrelated patients with craniofacial dysmorphism, with or without mental retardation, one 36-year-old man had a nonsynonymous mutation in SATB2. The affected individual exhibited craniofacial dysmorphisms including cleft palate, generalized osteoporosis, profound mental retardation, epilepsy and a jovial personality. He carries a de novo germline nonsense mutation (c.715C>T, p.R239X) in the exon 6 of SATB2. Expression studies showed that the mutant RNA was stable, expected to produce a truncated protein predicted to retain its dimerization domain and exert a dominant negative effect. This new syndrome is the first determined to result from mutation of a gene within the family that encodes nuclear matrix-attachment region (MAR) proteins.
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PMID:Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects. 1737 62

The characteristic slowness of movement initiation and execution in adult individuals with mental retardation may be driven by the slower frequency profile of the dynamics of the system. To investigate this hypothesis, we examined the resting and postural finger tremor frequency profile (single and dual limb) of adults as a function of level of mental retardation (moderate, severe, profound). There was a progressive increase in the contribution of slow frequency components to the enhanced amplitude of tremor as a function of mental retardation, particularly in the group with profound mental retardation. Findings support the hypothesis of mental retardation inducing a slower frequency to the system dynamics that may fundamentally drive the characteristic slowness of movement behavior.
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PMID:Tremor frequency profile as a function of level of mental retardation. 1755 96

The aim of the present study was to assess the behavioral and cognitive effects following treatment with topiramate in children and adolescents with epilepsy with mild to profound mental retardation. The study group comprised 29 children, 16 males and 13 females, aged 3 to 19 years, affected by partial (4) and generalized (25) crypto/symptomatic epilepsy and mental retardation (7 mild, 5 moderate, 15 severe, 2 profound), who were administered topiramate (TPM) as add-on therapy to their baseline antiepileptic treatment. At baseline, 3 months, 6 months, and 12 months, parents or caregivers of each patient were administered a questionnaire based on the Holmfrid Quality of Life Inventory. After a 3-month follow-up, the add-on topiramate caused overall mild to moderate cognitive/behavioral worsening in about 70% of children and adolescents with mental retardation and epilepsy. After 6 and 12 months of follow-up, global worsening persisted in 31 and 20.1% of cases, respectively. In conclusion, this trial confirms that TPM can have significant adverse cognitive and behavioral side effects, even in mentally disabled children and adolescents.
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PMID:Topiramate in children and adolescents with epilepsy and mental retardation: a prospective study on behavior and cognitive effects. 1796 81

One woman with profound mental retardation and spasticity living in a public residential developmental center was treated with intrathecal baclofen therapy and botulinum toxin type A injections. After one year of regular injections, extension across the right elbow increased 49 degrees. After one year of ITB, range of motion for left hip abduction increased 28 degrees; right hip abduction 9 degrees; left hip flexion 3 degrees; right hip flexion 1 degree; right knee flexion 31 degrees. Our case demonstrates the importance of a multidisciplinary approach in order to ease care and prevent complications. Expanded investigations should be carried out to evaluate the efficacy of combined therapy in patients with mental retardation.
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PMID:Combined treatment with BTX-A and ITB for spasticity: case report. 1796 16

Dysequilibrium syndrome is a genetically heterogeneous condition that combines autosomal recessive, nonprogressive cerebellar ataxia with mental retardation. Here, we report the first patient heterozygous for 2 novel mutations in VLDLR. An 18-month-old girl presented with significant hypotonia, global developmental delay, and truncal and peripheral ataxia. Magnetic resonance imaging of the brain demonstrated hypoplasia of the inferior cerebellar vermis and hemispheres, small pons, and a simplified cortical sulcation pattern. Sequence analysis of the VLDLR gene identified a nonsense and missense mutation. Six mutations in VLDLR have now been identified in 5 families with a phenotype characterized by moderate-to-profound mental retardation, delayed ambulation, truncal and peripheral ataxia, and occasional seizures. Neuroanatomically, the loss-of-function effect of the different mutations is indistinguishable. VLDLR-associated cerebellar hypoplasia is emerging as a panethnic, clinically, and molecularly well-defined genetic syndrome.
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PMID:Mutations in VLDLR as a cause for autosomal recessive cerebellar ataxia with mental retardation (dysequilibrium syndrome). 1933 71

X-linked alpha-thalassemia/mental retardation syndrome (ATR-X syndrome, OMIM #301040) is one of the syndromes associated with abnormal epigenetic gene regulation, including ICF(DNMT3B), Rett (MECP2), Rubinstein-Taybi (CBP), Coffin-Lowry (RSK2), and Sotos (NSD1) syndromes. It is a syndromic form of X-linked mental retardation, which affects males and is characterized by profound mental retardation, mild HbH disease (alpha-thalassemia), facial dysmorphism, skeletal abnormalities, and autistic behavior. ATR-X syndrome is caused by a mutation in the ATRX gene on the X chromosome (Xq13), which encodes ATRX protein, belonging to the SNF2 family of chromatin-remodeling proteins. The protein has two functionally important domains: an ADD (ATRX-DNMT3-DNMT3L) domain at the N-terminus, and chromatin-remodeling domain in the C-terminal half, where the ATRX gene mutations of most ATR-X patients reside. Perturbation in DNA methylation in the rDNA genes was repored in ATR-X patients, and ATRX protein is presumed to be involved in the establishment and maintenance of DNA methylation. Based on its various clinical phenotypes, the expressions of many genes, including alpha globin genes, seem to be abnormally regulated in ATR-X patients. However, the precise mechanism involving ATRX protein remains to be elucidated. Epigenetics can link environmental and genetic causes of many pathological conditions. The genes, which are abnormally regulated by a perturbed epigenetic mechanism, are, in themselves, structurally normal, and the elucidation of their mechanism may lead to the development of appropriate therapy.
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PMID:[X-linked alpha-thalassemia/mental retardation syndrome]. 1948 41

In this review, we detail the history, molecular diagnosis, epidemiology, and clinical features of the MECP2 duplication syndrome, including considerations for the care of patients with this X-linked neurodevelopmental disorder. MECP2 duplication syndrome is 100% penetrant in affected males and is associated with infantile hypotonia, severe to profound mental retardation, autism or autistic features, poor speech development, recurrent infections, epilepsy, progressive spasticity, and, in some cases, developmental regression. Most of the reported cases are inherited, however, de novo cases have been documented. While carrier females have been reported to be unaffected, more recent research demonstrates that despite normal intelligence, female carriers display a range of neuropsychiatric phenotypes that pre-date the birth of an affected son. Given what we know of the syndrome to date, we propose that genetic testing is warranted in cases of males with infantile hypotonia and in cases of boys with mental retardation and autistic features with or without recurrent infections, progressive spasticity, epilepsy, or developmental regression. We discuss recommendations for clinical management and surveillance as well as the need for further clinical, genotype-phenotype, and molecular studies to assist the patients and their families who are affected by this syndrome.
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PMID:The MECP2 duplication syndrome. 2042 14


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