Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autistic disorder and catatonia are neuropsychiatric syndromes defined by impairments in social interaction, communication, and restricted, stereotypical motor routines. Assessments of children with these disorders are typically restricted in scope by the patients' limited ability to comprehend directions. The authors performed systematic assessments of dyskinesias on six prepubertal boys with autistic disorder and mental retardation and on one adolescent male with catatonia to determine if this type of information could be routinely obtained. The boys with autistic disorder had more stereotypies and tics, a greater degree of akathisia and hyperactivity, and more compulsions than the adolescent with catatonia. Catatonia was associated with catalepsy and dystonic postures. The authors conclude that the diagnostic accuracy and specificity of neuropsychiatric syndromes may be enhanced by the systematic assessment of the dyskinesias associated with each condition.
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PMID:Dyskinesias differentiate autistic disorder from catatonia. 1754 61

To characterize further the clinical features and long-term outcomes among children with motor stereotypies who do not manifest mental retardation or pervasive developmental disorders, a review of clinical records and semistructured telephone interviews were undertaken. The identified clinical cohort consisted of 100 typically developing children with motor stereotypies. The mean length of follow-up was 6.8 +/- 4.6 years. At most recent follow-up, movements had continued in 94% of the sample (62% for >5 years). Only six children reported complete cessation of movements, with four (3 of 4 with head nodding) doing so >1 year after their initial diagnosis. Thus the course of motor stereotypies, especially in children with arm/hand movements, appears chronic. Nearly half the children in this cohort exhibit other comorbidities, including attention-deficit-hyperactivity disorder (30%), tics (18%), and obsessive-compulsive behaviors/obsessive-compulsive disorder (10%). Twenty-five percent of children with motor stereotypies reported positive family histories of motor stereotypies, suggesting an underlying genetic abnormality. Finally, evidence is emerging that the clinical course of children who exhibit head nodding may differ from those whose motor stereotypy predominantly involves the hands and arms.
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PMID:Nonautistic motor stereotypies: clinical features and longitudinal follow-up. 1835 6

Rett syndrome is a genetic neurodevelopmental disorder that affects mainly girls, but mutations in the causative MECP2 gene have also been identified in boys with classic Rett syndrome and Rett syndrome-like phenotypes. We have studied a group of 28 boys with a neurodevelopmental disorder, 13 of which with a Rett syndrome-like phenotype; the patients had diverse clinical presentations that included perturbations of the autistic spectrum, microcephaly, mental retardation, manual stereotypies, and epilepsy. We analyzed the complete coding region of the MECP2 gene, including the detection of large rearrangements, and we did not detect any pathogenic mutations in the MECP2 gene in these patients, in whom the genetic basis of disease remained unidentified. Thus, additional genes should be screened in this group of patients.
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PMID:Mutations in the MECP2 gene are not a major cause of Rett syndrome-like or related neurodevelopmental phenotype in male patients. 1916 18

The 9q Subtelomeric Deletion Syndrome (9qSTDS) is clinically characterized by mental retardation, childhood hypotonia, and facial dysmorphisms. Haploinsufficiency of the EHMT1 gene has been demonstrated to be responsible for its core phenotype. In a significant number of patients behavioral abnormalities like aggression, impulsivity, and chaotic behaviors are present as well as epileptic phenomena. Reports about the developmental, behavioral, and neuropsychiatric aspects of 9qSTDS are scarce and mostly limited to young patients only. In this report, the behavioral and neuropsychiatric characteristics of one male and one female middle-aged patient are described in whom the genetic diagnosis, interstitial and telomeric 9q deletion, respectively, was established recently. In both patients a remarkable sleep disturbance, characterized by frequent awakenings and daytime sleepiness, was present as well as a prominent apathy syndrome. The observed motor signs such as rigid flexure of the arms and finger stereotypies persisted over a period of many years and could therefore not be viewed as symptoms of catatonia. It is concluded that the proposed behavioral phenotype of 9qSTDS comprises at least an erratic sleep pattern and an enduring severe apathy.
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PMID:Behavioral phenotype in the 9q subtelomeric deletion syndrome: a report about two adult patients. 1964 12

Methyl CpG binding protein-2 (MeCP2) is an essential epigenetic regulator in human brain development. Rett syndrome, the primary disorder caused by mutations in the X-linked MECP2 gene, is characterized by a period of cognitive decline and development of hand stereotypies and seizures following an apparently normal early infancy. In addition, MECP2 mutations and duplications are observed in a spectrum of neurodevelopmental disorders, including severe neonatal encephalopathy, X-linked mental retardation, and autism, implicating MeCP2 as an essential regulator of postnatal brain development. In this review, we compare the mutation types and inheritance patterns of the human disorders associated with MECP2. In addition, we summarize the current understanding of MeCP2 as a central epigenetic regulator of activity-dependent synaptic maturation. As MeCP2 occupies a central role in the pathogenesis of multiple neurodevelopmental disorders, continued investigation into MeCP2 function and regulatory pathways may show promise for developing broad-spectrum therapies.
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PMID:The role of MeCP2 in brain development and neurodevelopmental disorders. 2042 98

Genome-wide high-resolution array analysis is rapidly becoming a reliable method of diagnostic investigation in individuals with mental retardation and congenital anomalies, leading to the identification of several novel microdeletion and microduplication syndromes. We have identified seven individuals with duplication on chromosome 14q11.2q13.1, who exhibited idiopathic developmental delay and cognitive impairment, severe speech delay, and developmental epilepsy. Among these cases, the minimal common duplicated region on chromosome 14q11.2q13.1 includes only three genes, FOXG1, C14orf23, and PRKD1. We propose that increased dosage of Forkhead Box G1 (FOXG1) is the best candidate to explain the abnormal neurodevelopmental phenotypes observed in our patients. Deletions and inactivating mutations of FOXG1 have been associated with a Rett-like syndrome characterized by hypotonia, irritability, developmental delay, hand stereotypies, and deceleration of head growth. FOXG1, encoding a brain-specific transcription factor, has an important role in the developing brain. In fact, in vivo studies in chicken brain demonstrated that overexpression of FOXG1 results in thickening of the neuroepithelium and outgrowth of the telencephalon and mesencephalum, secondary to a reduction in neuroepithelial cell apoptosis.
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PMID:Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment. 2225 24

Loss-of-function mutations of the MECP2 gene are the cause of most cases of Rett syndrome in females, a progressive neurodevelopmental disorder characterized by severe mental retardation, global regression, hand stereotypies, and microcephaly. On the other hand, gain of dosage of this gene causes the MECP2 duplication syndrome in males characterized by severe mental retardation, absence of speech development, infantile hypotonia, progressive spasticity, recurrent infections, and facial dysmorphism. Female carriers of a heterozygous duplication show a skewed X-inactivation pattern which is the most probable cause of the lack of clinical symptoms. In this paper, we describe a girl with a complex de novo copy number gain at Xq28 and non-skewed X-inactivation pattern that causes mental retardation and motor and language delay. This rearrangement implies triplication of the MECP2 and IRAK1 genes, but it does not span other proximal genes located in the common minimal region of patients affected by the MECP2 duplication syndrome. We conclude that the triplication leads to a severe phenotype due to random X-inactivation, while the preferential X chromosome inactivation in healthy carriers may be caused by a negative selection effect of the duplication on some proximal genes like ARD1A or HCFC1.
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PMID:De novo interstitial triplication of MECP2 in a girl with neurodevelopmental disorder and random X chromosome inactivation. 2193 80

Rett syndrome (RTT) is a neurodevelopmental disorder that is one of the most common causes of mental retardation in females. RTT diagnosis is based on distinct clinical criteria. We describe here a female patient with severe phenotype of congenital variant RTT. The patient originally presented with severe developmental delay prior to the age of 6 months and later exhibited characteristic features of RTT that included air swallowing, bruxism, and hand stereotypies. Results of an array-based comparative genomic hybridization analysis indicated there was a very small microdeletion in Xq28. Multiplex ligation-dependent probe amplification analysis further confirmed there were heterozygous deletions of intron 2, exon 3, intron 3, and part of exon 4 in MECP2. Findings in the present patient confirm the view that large MECP2 deletions are an important cause of severe congenital variant RTT. To ensure an accurate diagnosis of congenital variant RTT, a multiplex ligation-dependent probe amplification analysis of MECP2 should be performed in patients suspected of having this disorder.
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PMID:Congenital variant of Rett syndrome due to an intragenic large deletion in MECP2. 2200

We have recently described four principal pathogenetic components in autism: (I) circadian and sensory dysfunction, (II) immune abnormalities, (III) neurodevelopmental delay, and (IV) stereotypic behaviors. Using hierarchical and k-means clustering, the same 245 patients assessed in our principal component analysis can be partitioned into four clusters: (a) 43 (17.6%) have prominent immune abnormalities accompanied by some circadian and sensory issues; (b) 44 (18.0%) display major circadian and sensory dysfunction, with little or no immune symptoms; (c) stereotypies predominate in 75 (31.0%); and (d) 83 (33.9%) show a mixture of all four components, with greater disruptive behaviors and mental retardation. The "immune" component provides the largest contributions to phenotypic variance (P = 2.7 x 10(-45)), followed by "stereotypic behaviors." These patient clusters may likely differ in genetic and immune underpinnings, developmental trajectories, and response to treatment.
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PMID:Cluster analysis of autistic patients based on principal pathogenetic components. 2243 Dec 51

Stereotypies have been defined as non-goal-directed movement patterns repeated continuously for a period of time in the same form and on multiple occasions, and which are typically distractible. Stereotypical motor behaviors are a common clinical feature of a variety of neurological conditions that affect cortical and subcortical functions, including autism, tardive dyskinesia, excessive dopaminergic treatment of Parkinson's disease and frontotemporal dementia. The main differential diagnosis of stereotypies includes tic disorders, motor mannerisms, compulsion and habit. The pathophysiology of stereotypies may involve the corticostriatal pathways, especially the orbitofrontal and anterior cingulated cortices. Because antipsychotics have long been used to manage stereotypical behaviours in mental retardation, stereotypies that present in isolation tend not to warrant pharmacological intervention, as the benefit-to-risk ratio is not great enough.
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PMID:Adult-onset stereotypical motor behaviors. 2749 41


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