Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two familial X-linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X-linked transmission. On the other hand, the pedigrees of 2 families ruled out X-linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X-linked syndrome of cortical maldevelopment.
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PMID:Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment. 1089 14

The term acanthocytosis is derived from the Greek for "thorn" and is used to describe a peculiar spiky appearance of erythrocytes. Acanthocytosis is found to be associated with at least three hereditary neurological disorders that are generally referred to as neuroacanthocytosis. Abetalipoproteinaemia is an autosomal recessive condition, characterised by absence of serum apolipoprotein B containing lipoproteins leading to fat intolerance and fat-soluble vitamin deficiency. This results in a progressive spinocerebellar ataxia with peripheral neuropathy and retinitis pigmentosa. Chorea-acanthocytosis is also an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysphagia, dysarthria, areflexia, seizures and dementia. Some of its features, including choreic movements, peripheral neuropathy with areflexia, elevated serum creatine kinase levels and myopathy are shared by another form of neuroacanthocytosis, McLeod syndrome. Patients affected by this X-linked disorder also show abnormal expression of Kell blood group antigens and a permanent haemolytic state. In addition to these cases, acanthocytosis is occasionally associated with other neurological disorders, such as Hallervorden-Spatz disease. For each of the neuroacanthocytosis syndromes we review the main clinical features and their molecular bases. The recent molecular genetics findings are the first step towards the understanding of the pathogenetic mechanisms and eventually the search for effective treatments.
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PMID:Clinical features and molecular bases of neuroacanthocytosis. 1218 48

X-linked Charcot-Marie-Tooth disease (CMTX) is a hereditary demyelinating neuropathy caused by mutations in the connexin 32 (Cx32) gene. Cx32 is widely expressed in brain and peripheral nerve, yet clinical manifestations of CMTX mainly arise from peripheral neuropathy. We have evaluated two male patients with CMTX who on separate occasions developed transient ataxia, dysarthria, and weakness within 3 days of returning from ski trips at altitudes above 8,000 feet. Magnetic resonance imaging studies in both patients showed nonenhancing, confluent, and symmetrical white matter abnormalities that were more pronounced posteriorly and that resolved over several months. Magnetic transfer images in one patient demonstrated increased magnetization transfer ratios distinct from that seen in demyelination or edema. Both patients returned to their normal baseline within 2 to 3 weeks. These cases suggest that CMTX patients are at risk for developing an acute, transient, neurological syndrome when they travel to places at high altitudes and return to sea level. Cx32 mutations may cause central nervous system dysfunction by reducing the number of functioning gap junctions between oligodendrocytes and astrocytes, making both cells more susceptible to abnormalities of intercellular exchange of ions and small molecules in situations of metabolic stress.
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PMID:Transient central nervous system white matter abnormality in X-linked Charcot-Marie-Tooth disease. 1232 71

Partington et al. [1988] described a three-generation family (MRXS1, MIM *309510, PRTS) with a syndromic form of X-linked mental retardation (XLMR). The clinical features in 10 affected males included mild to moderate MR, dystonic movements of the hands, and dysarthria. After refinement, the PRTS locus was mapped to marker DXS989 (with maximum LOD score of 3.1) with flanking markers DXS365 and DXS28. Since then, no other patients with a similar phenotype have been described. We present a detailed description of the neurological symptoms and the disease history of two brothers with the clinical features of PRTS. Psychomotor development was delayed in both, and neurological features included mild to moderate mental retardation, dysarthria, facial muscle weakness, severe dysdiadochokinesis, slow dystonic movements, and mild spasticity of the hands, without ataxia or spasticity of the legs. The symptoms were nonprogressive and extrapyramidal, and without cerebellar involvement. In general, behavior of the two brothers was friendly and quiet, although the elder brother had periods of depressed mood and outbursts of anger. Karyotypes and subsequent investigation of the subtelomeres as well as DNA analysis of the FMR1 gene, the androgen receptor gene, and the DM locus did not reveal a genetic abnormality. Haplotype analysis showed that the affected brothers share the PRTS region at Xp22.1. Mutation screening of the PDH-E1alpha gene did not reveal a pathogenic mutation.
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PMID:Clinical study and haplotype analysis in two brothers with Partington syndrome. 1237 38

The clinico-pathological study of a new type of familial parkinsonism with striatal degeneration is reported. The inheritance mode was autosomal recessive, and three out of four offspring of married cousins developed parkinsonism in their early adulthood. Their clinical signs were rigidity, bradykinesia, postural instability and dysarthria. These symptoms were slowly progressive and responsive to levodopa therapy to a variable degree. On cerebral magnetic resonance imaging, T2 and proton density-weighted images showed hyperintensity in the bilateral putamina. The neuropathological study of one case revealed atrophy of the bilateral putamina and caudate nuclei, and a severe neuronal loss and gliosis in the putamina. Patchy mosaicism of normal and degenerated tissue was observed in the putamina. A similar mode of the degeneration was mildly seen in the caudate nuclei. The substantia nigra showed atrophy of the pars reticulata, and mild to moderate neuronal loss of the pars compacta with rostral dominance, but no Lewy bodies were observed. These neuropathological findings differed from those of Parkinson's disease or juvenile parkinsonism, but mimic to those of X-linked dystonia parkinsonism (Lubag). It seems that this familial bilateral striatal degeneration is a new variant of familial parkinsonism.
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PMID:Clinico-pathological study of a case of familial parkinsonism with striatal degeneration. 1247 65

Three families with X-linked mental retardation caused by a 24 base-pair duplication in ARX[428-451dup(24 bp)] are reported. The clinical features in these and six other published families are reviewed. In general, the clinical picture is variable. Mental retardation ranges from mild to severe. Infantile spasms (West syndrome) occurred in 12.5% and other less severe forms of seizures in 37.5%. Characteristic dystonic movements of the hands were seen in 63% and dysarthria in 54%. The focal dystonia, in association with mental retardation, may prove to be diagnostic of this mutation.
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PMID:Three new families with X-linked mental retardation caused by the 428-451dup(24bp) mutation in ARX. 1520 May 6

Spinobulbar muscular atrophy (SBMA) is an X-linked form of motor neuron disease characterized by progressive atrophy of the muscles, dysphagia, dysarthria and mild androgen insensitivity. SBMA is caused by CAG repeat expansion in the androgen receptor gene. CAG repeat polymorphism was analysed in a Polish control group (n = 150) and patients suspected of SBMA (n = 60). Normal and abnormal ranges of CAG repeats were established in the control group and in 21 patients whose clinical diagnosis of SBMA was molecularly confirmed. The ranges are similar to those reported for other populations.
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PMID:CAG repeat polymorphism in the androgen receptor (AR) gene of SBMA patients and a control group. 1587 92

Thyroid hormones are known to be essential for growth, development and metabolism. Recently mutations in the SLC16A2 gene coding for the monocarboxylate thyroid hormone transporter 8, MCT8, have been associated with Allan-Herndon-Dudley syndrome (AHDS), an X-linked condition characterized by severe mental retardation, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia. Here we describe in detail the clinical and biochemical features in a boy affected by AHDS with severe neurological abnormalities and a novel de novo SLC16A2 gene insertion, 1343-1344insGCCC, resulting in a truncated protein lacking the last four transmembrane domains (TMDs) as well as the carboxyl cytoplasmic end. He presents mental retardation, axial hypotonia, hypertonia of arms and legs, paroxysmal dyskinesias, seizures. The endocrine phenotype showed low serum total and free thyroxine (T4), very elevated total and free triiodothyronine (T3) and normal thyrotropin (TSH) with blunted response to thyrotropin-releasing hormone (TRH). The latter finding was unexpected and suggested that the lack of functional MCT8 was counterbalanced at the thyrotrope cell level by high serum T3 concentration and/or by increased intrapituitary type 2 deiodinase (D2) activity. Our case constitutes a relevant contribution to better characterize this disorder and to elucidate the functional consequences of SLC16A2 gene mutations.
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PMID:Allan-Herndon-Dudley syndrome (AHDS) caused by a novel SLC16A2 gene mutation showing severe neurologic features and unexpectedly low TRH-stimulated serum TSH. 2071 92

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelination disorder of the central nervous system (CNS). PMD is caused by mutations in the PLP1 gene located at Xq22 and encoding the major myelin component in CNS, proteolipid protein 1 (PLP1). The disease is clinically heterogeneous. Phenotypes are generally categorized into classic and connatal forms. Connatal PMD has more rapid progression with early death, while patients with classic PMD generally survive to adulthood. Both forms of the disease are caused by point mutations as well as rearrangements - multiplication (mainly duplication) and deletion of the PLP1 gene. We present a case of a male patient affected by the classic form of PMD with benign course, except severe dysarthria with the characteristic laryngeal stridor, which is more typical for connatal form of the disease. The diagnosis has been confirmed at the molecular level. The patient has duplication of all 7 exons of the PLP1 gene. This duplication was inherited from the patient's mother, who is an unaffected carrier of the mutation. The patient's family pedigree analysis revealed the interfamilial variability of the phenotype among affected male relatives.
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PMID:PLP1 gene duplication as a cause of the classic form of Pelizaeus-Merzbacher disease - case report. 2108 96

ARX mutations give rise to both syndromic and nonsyndromic forms of mental retardation (MR). We investigated the most common ARX mutations, c.428_451 dup(24bp) and c.333ins (GCG)7 in a series of 370 mentally retarded FMR1 (CGG)n expansion mutation negative Turkish patients using PCR amplification and high resolution MetaPhor agarose gel electrophoresis. Sequence analysis was also performed for confirmation and discrimination of the mutations. One patient representing non-syndromic X-linked MR showed an abnormal band pattern on agarose gel and sequence analysis of exon 2 of the ARX gene revealed that the patient had the c.428_451 dup(24bp) mutation. When we screened the family members, we found that his sister and mother were also carrier for the same mutation. The proband showed mild MR and subtle clinical findings like dysarthria and lack of fine motor functions. In conclusion, the patients with weak fine motor skills and positive family history for X-linked MR should be screened for the most common ARX gene mutations.
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PMID:C.428_451 dup(24bp) mutation of the ARX gene detected in a Turkish family. 2307 84


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