Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper describes three children of a Pakistani first cousin marriage with a distinctive, non-progressive disorder characterised by variable phalangeal anomalies, microcephaly, pre- and postnatal growth retardation, poor vision, dystonic movements, a characteristic face, and severe mental retardation. This combination of features seems to be distinct and to represent a new autosomal recessive syndrome.
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PMID:Three sibs with phalangeal anomalies, microcephaly, severe mental retardation, and neurological abnormalities. 164 Apr 33

Three severely asphyxiated full-term newborns showed tomographic findings of bilateral symmetrical hyperdensities restricted to the thalamic region. All these patients had a strikingly similar poor neurological outcome characterized by dystonia, severe mental retardation and acquired microcephaly. We presume that these bithalamic hyperdensities could be an early predictor of the later status marmoratus.
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PMID:Symmetrical bithalamic hyperdensities in asphyxiated full-term newborns: an early indicator of status marmoratus. 328 25

Two siblings with atypical methylmalonic aciduria and progressive encephalopathy are reported. Initial symptoms were failure to thrive and growth retardation from the first year of life, progressing to severe mental retardation, microcephaly, dystonia, spasticity and cataracts. The amount of methylmalonic acid excreted in the urine was substantially lower than in classical methylmalonic acidemia and was not reduced by vitamin B12 therapy. The activity of methylmalonyl-CoA mutase and the overall assay of propionic acid metabolism in cultured fibroblasts were normal. The primary defect in this probably new autosomal recessive disorder associated with methylmalonic aciduria is currently not known.
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PMID:Atypical methylmalonic aciduria with progressive encephalopathy, microcephaly and cataract in two siblings--a new recessive syndrome? 758 37

We report on a 2.5-year-old boy with severe mental retardation, choreoathetosis, dystonia, muscle rigidity, opisthotonus and severe hearing impairment. He had history of severe hyperbilirubinaemia immediately after birth presumably due to ABO incompatibility. The history and the clinical picture suggested the diagnosis of Kernicterus. The MR imaging examination upon admission revealed bilateral signal intensity increase in the globus pallidum on T2-weighted sequences. Additionally, our patient showed signal intensity changes within the subthalamic nuclei, which is known to be another characteristic area of bilirubin deposition in Kernicterus.
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PMID:MR findings in a patient with Kernicterus. 1060 75

Two families, originally diagnosed as having nonsyndromic X-linked mental retardation (NSXLMR), were reviewed when it was shown that they had a 24-bp duplication (428-45 1dup(24bp)) in the ARX gene [Stromme et al., 2002: Nat Genet 30:441-445]. This same duplication had also been found in three other families: one with X-linked infantile spasms and hypsarrhythmia (X-linked West syndrome, MIM 308350) and two with XLMR and dystonic movements of the hands (Partington syndrome, MIM 309510). On review, manifestations of both West and Partington syndromes were found in some individuals from both families. In addition, it was found that one individual had autism and two had autistic behavior, one of whom had epilepsy. The degree of mental retardation ranged from mild to severe. A GCG trinucleotide expansion (GCG)10+7 and a deletion of 1,517 bp in the ARX gene have also been found in association with the West syndrome, and a missense mutation (1058C>T) in a family with a newly recognized form of myoclonic epilepsy, severe mental retardation, and spastic paraplegia [Scheffer et al., 2002: Neurology, in press]. Evidently all these disorders are expressions of mutations in the same gene. It remains to be seen what proportions of patients with infantile spasms, focal dystonia, autism, epilepsy, and nonsyndromic mental retardation are accounted for by mutations in the ARX gene.
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PMID:Variable expression of mental retardation, autism, seizures, and dystonic hand movements in two families with an identical ARX gene mutation. 1237 46

Mutations in the MECP2 (methyl-CpG-binding protein 2) gene are known to cause Rett syndrome, a well-known and clinically defined neurodevelopmental disorder. Rett syndrome occurs almost exclusively in females and for a long time was thought to be an X-linked dominant condition lethal in hemizygous males. Since the discovery of the MECP2 gene as the cause of Rett syndrome in 1999, MECP2 mutations have, however, also been reported in males. These males phenotypically have classical Rett syndrome when the mutation arises as somatic mosaicism or when they have an extra X chromosome. In all other cases, males with MECP2 mutations show diverse phenotypes different from classical Rett syndrome. The spectrum ranges from severe congenital encephalopathy, mental retardation with various neurological symptoms, occasionally in association with psychiatric illness, to mild mental retardation only. We present a 21-year-old male with severe mental retardation, spastic tetraplegia, dystonia, apraxia and neurogenic scoliosis. A history of early hypotonia evolving into severe spasticity, slowing of head growth, breathing irregularities and good visual interactive behaviour were highly suggestive of Rett syndrome. He has a de novo missense mutation in exon 3 of the MECP2 gene (P225L). The clinical spectrum and molecular findings in males with MECP2 mutations are reviewed.
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PMID:Neurodevelopmental disorders in males related to the gene causing Rett syndrome in females (MECP2). 1261 69

Mutations in the ARX gene are responsible for a wide variety of mental retardation conditions including X-linked infantile spasms (ISSX) and generalized dystonia. However, electroclinical descriptions in patients with ISSX carrying ARX mutations are scarce. Here, we report on the electroclinical features of a 4-year-old boy with an expansion of the trinucleotide repeat in the ARX gene. Epilepsy started at 2 months of age with subclinical spasms that consisted of episodes of eye rolling combined with atypical hypsarrhythmia. Later, the condition evolved into severe mental retardation with polymorphic ictal episodes that consisted of nocturnal brief axial contractions followed by dyskinetic movement of all four limbs and diurnal clusters of chaotic movements combined with myoclonic jerks. EEG recording of these episodes lead to the diagnosis of non-ictal dyskinetic movements. This combination of early infantile spasms followed by a complex movement disorder contributes further to extent the pleiotropy of the ARX-linked "interneuronopathy" and should lead the clinician to ARX mutation screening.
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PMID:Combination of infantile spasms, non-epileptic seizures and complex movement disorder: a new case of ARX-related epilepsy. 1846 66

We have studied a family with severe mental retardation characterized by the virtual absence of speech, autism spectrum disorder, epilepsy, late-onset ataxia, weakness and dystonia. Post-mortem examination of two males revealed widespread neuronal loss, with the most striking finding being neuronal and glial tau deposition in a pattern reminiscent of corticobasal degeneration. Electron microscopic examination of isolated tau filaments demonstrated paired helical filaments and ribbon-like structures. Biochemical studies of tau demonstrated a preponderance of 4R tau isoforms. The phenotype was linked to Xq26.3, and further analysis identified an in-frame 9 base pair deletion in the solute carrier family 9, isoform A6 (SLC9A6 gene), which encodes sodium/hydrogen exchanger-6 localized to endosomal vesicles. Sodium/hydrogen exchanger-6 is thought to participate in the targeting of intracellular vesicles and may be involved in recycling synaptic vesicles. The striking tau deposition in our subjects reveals a probable interaction between sodium/proton exchangers and cytoskeletal elements involved in vesicular transport, and raises the possibility that abnormalities of vesicular targeting may play an important role in more common disorders such as Alzheimer's disease and autism spectrum disorders.
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PMID:A mutation affecting the sodium/proton exchanger, SLC9A6, causes mental retardation with tau deposition. 2039 63

The purpose of this study was to determine whether transplantation of umbilical cord blood from unrelated donors before the development of symptoms could halt the progression of early juvenile onset cases of MLD in whom the disease was diagnosed based on the family history. Three asymptomatic children (aged 2 years 4 months, 2 years 8 months and 5 years 5 months, two of whom were sisters) underwent unrelated umbilical cord blood transplantation (UCBT) and two untreated symptomatic siblings were included in the study. In 14-year and 6-year follow-ups after transplantation, clinical examination, ARSA enzyme levels, neurophysiological, neuroimaging, and psychological status were assessed. All three transplanted patients remain well, and the parameters evaluated remain stable. Of the treated patients, the two sisters had ongoing evidence of demyelinating sensorimotor neuropathy on nerve conduction tests, and with a early sensorimotor neuropathy in the older sister , and the other patient has mild intellectual impairment. One of the two un-transplanted controls, 15 years after MLD diagnosis, has relentlessly progressed to full dependency with epilepsy, severe mental retardation, dystonic movements, dysphagia and recurrent respiratory problems. Six years after diagnosis, the other control has a slowly progressive course with spastic dystonic quadriplegia, epilepsy, dysphagia, continual drooling and incontinence. Our data show that, in comparison with their untreated siblings, UCBT significantly slowed the progression of the disease in the treated patients. We conclude that UCBT benefits children with pre-symptomatic early juvenile onset MLD by favourably altering the natural history of the disease.
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PMID:Outcome of Early Juvenile Onset Metachromatic Leukodystrophy After Unrelated Cord Blood Transplantation: A Case Series and Review of the Literature. 2618 19