Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angelman syndrome (AS) is a distinct neurogenetic disorder and the phenotype is well known in childhood and adolescence. However, with advancing age the clinical and behavioral phenotype changes. In adulthood, the phenotype can be rather aspecific. We report on AS in 3 severely to profoundly mentally retarded patients, who developed severe neurologic complications of severe tremor, spasticity and coordination problems, resulting into severe loss of function. They presented atypical craniofacial features, short stature, epileptic seizures, microcephaly, brachytelephalangy and absent speech. Two patients presented at an older age a change in day-night rhythm. Based on this experience, we conclude that all severely to profoundly mentally retarded patients with atypical phenotype, spasticity, absent speech, epileptic seizures and changed day-night rhythm are candidates for further cytogenetic and molecular investigation for AS. Clinical photographs of the patient at a younger age can be helpful. The presence of the typical EEG pattern with frontal triphasic delta waves may direct to the diagnosis of AS.
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PMID:Angelman syndrome in three adult patients with atypical presentation and severe neurological complications. 1114 Apr 14

The aim of this study was to examine the character of motor dysfunction in individuals with Angelman syndrome (AS). Thirty-three children and adolescents (median age 6 years, range 18 months to 23 years) were consecutively investigated for learning disability, epilepsy, and motor dysfunction to detect suspected AS. Twenty-three individuals (13 males, 10 females; median age 5 years 6 months, range 21 months to 23 years) fulfilled international consensus criteria for AS. Clinical diagnosis was supported by a positive DNA methylation test in eleven participants. Ten participants (seven males, three females; median age six years, range 18 months to 13 years) did not comply with consensus criteria for AS and were regarded as a comparison group. There was no significant difference between the AS and the comparison group regarding age or developmental level. Median developmental quotient level was 26 months (range 8 to 63 months); median gross motor developmental level in participants with AS was 24 months (range 8 to 60 months); median fine motor developmental level was 15 months (range 6 to 60 months). Muscle strength, spasticity, tremor, and coactivation were assessed: distal lower limb spasticity, ataxic like gait, stiff lower limbs, and the presence of coactivation during locomotion were significantly more frequent in participants with AS than in the comparison group (p<0.05). Asymmetry of muscle strength and spasticity were frequent. Neurological abnormalities were insufficient for a diagnosis of cerebral palsy and impeded function less than immaturity in both AS groups. Risk of increasing impairment needs to be anticipated to prevent negative long-term effects of muscle imbalance and motor asymmetries in individuals with AS.
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PMID:Motor impairments, neurological signs, and developmental level in individuals with Angelman syndrome. 1570 39

Mutations have been found in the UBE3A gene (E6-AP ubiquitin protein ligase gene) in many Angelman syndrome (AS) patients with no deletion, no uniparental disomy, and no imprinting defect. UBE3A mutations are more frequent in familial than in sporadic patients and the mutations described so far seem to cause similar phenotypes in the familial affected cases. Here we describe two first cousins who have inherited the same UBE3A frameshift mutation (duplication of GAGG in exon 10) from their asymptomatic mothers but present discordant phenotypes. The proband shows typical AS features. Her affected cousin shows a more severe phenotype, with asymmetric spasticity that led originally to a diagnosis of cerebral palsy. Proband's brain MRI shows mild cerebral atrophy while her cousin's brain MRI shows severe brain malformation. This family demonstrates that, although brain malformation is unusual in AS, presence of a brain malformation does not exclude the diagnosis of AS. Also, this UBE3A mutation was transmitted from the cousin's grandfather to only two sisters among eight full siblings, raising the hypothesis of mosaicism for this mutation.
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PMID:Discordant phenotypes in first cousins with UBE3A frameshift mutation. 1515 Jul 76

The hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterised by lower limb spasticity and weakness. Mutations in NIPA1 (Nonimprinted in Prader-Willi/Angelman syndrome 1) have recently been identified as a cause of autosomal dominant pure HSP, with one mutation described in two unrelated families. NIPA1 has no known function but is predicted to possess nine transmembrane domains and may function as a receptor or transporter. Here we present a large British pedigree in which linkage analysis conclusively demonstrates linkage to the NIPA1 locus (maximum multipoint LOD score 4.6). Subsequent mutation analysis identified a novel missense substitution in a highly conserved NIPA1 residue (G106R) which further confirms a causative link between NIPA1 mutation and autosomal dominant hereditary spastic paraplegia.
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PMID:A novel NIPA1 mutation associated with a pure form of autosomal dominant hereditary spastic paraplegia. 1571 26

Christianson syndrome is an X-linked mental retardation syndrome characterized by microcephaly, impaired ocular movement, severe global developmental delay, hypotonia which progresses to spasticity, and early onset seizures of variable types. Gilfillan et al.2008] reported mutations in SLC9A6, the gene encoding the sodium/hydrogen exchanger NHE6, in the family first reported and in three others. They also noted the clinical similarities to Angelman syndrome and found cerebellar atrophy on MRI and elevated glutamate/glutamine in the basal ganglia on MRS. Here we report on nonsense mutations in two additional families. The natural history is detailed in childhood and adult life, the similarities to Angelman syndrome confirmed, and the MRI/MRS findings documented in three affected boys.
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PMID:Natural history of Christianson syndrome. 2094 24

Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity and weakness in the lower extremities that result from length-dependent central to peripheral axonal degeneration. Mutations in the non-imprinted Prader-Willi/Angelman syndrome locus 1 (NIPA1) transmembrane protein cause an autosomal dominant form of HSP (SPG6). Here, we report that transgenic (Tg) rats expressing a human NIPA1/SPG6 mutation in neurons (Thy1.2-hNIPA1) show marked early onset behavioral and electrophysiologic abnormalities. Detailed morphologic analyses reveal unique histopathologic findings, including the accumulation of tubulovesicular organelles with endosomal features that start at axonal and dendritic terminals, followed by multifocal vacuolar degeneration in both the CNS and peripheral nerves. In addition, the NIPA1 mutation in the spinal cord from older Tg rats results in an increase in bone morphogenetic protein type II receptor expression, suggesting that its degradation is impaired. This Thy1.2-hNIPA1 Tg rat model may serve as a valuable tool for understanding endosomal trafficking in the pathogenesis of a subgroup of HSP with an abnormal interaction with bone morphogenetic protein type II receptor, as well as for developing potential therapeutic strategies for diseases with axonal degeneration and similar pathogenetic mechanisms.
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PMID:Pathogenesis of autosomal dominant hereditary spastic paraplegia (SPG6) revealed by a rat model. 2412 79