1/42. A large Japanese family with machado-joseph disease: clinical and genetic analysis.We report clinical and genetic studies on a large Japanese family with machado-joseph disease (MJD), in which various different clinical phenotypes were seen in the same family, i.e., cerebellar ataxia type, severe amyotrophy type, and young-onset parkinsonism type. In addition, patients with very mild symptoms (formes frustes) were encountered. The expansion of the CAG repeat at the MJD locus ranged from 64 to 71 in 7 affected and 4 presymptomatic individuals. In our family, no clear inverse correlation was noted between the length of CAG-expansion and the age of onset, or the clinical phenotypes. Hyporeflexia was a common manifestation seen in 5 patients. It has been reported that the presence of peripheral neuropathy in MJD is associated with smaller increase in the CAG repeats; findings in our family conform with this observation.- - - - - - - - - - ranking = 1keywords = family (Clic here for more details about this article) |
2/42. Hyperekplexia phenotype due to compound heterozygosity for GLRA1 gene mutations.Hyperekplexia (MIM 149400), or startle disease, is a neurological disorder characterized by generalized stiffness during the neonatal period, excessive startle reflexes, and generalized stiffness related to the startle response. Linkage analysis mapped a major gene for this disorder to chromosome 5q33-35. Subsequently, mutations in the GLRA1 gene, encoding the alpha1 subunit of the glycine receptor, were found in hyperekplexia families with an autosomal dominant or recessive inheritance pattern. In the present study, we describe the genetic analysis of the GLRA1 gene of a family consisting of 2 children with hyperekplexia, 2 nonaffected children, and their healthy nonconsanguineous parents. Although the pedigree suggested the presence of a recessive mutation, haplotype construction showed that the 2 affected children shared the same haplotype combination in which the maternal haplotype differed from the paternal haplotype, suggesting the presence of compound heterozygosity. mutation analysis revealed different missense mutations on the two haplotypes, changing an arginine to a histidine at amino acid positions 252 and 392, respectively. It is interesting that the hyperekplexia phenotype was only seen in individuals compound heterozygous for the two mutations, whereas family members carrying either one of the two mutations had no clinical signs.- - - - - - - - - - ranking = 0.2690489906269keywords = family, family member, member (Clic here for more details about this article) |
3/42. Hypertonia, hyperreflexia, and excessive startle response in a neonate.Following an uneventful gestation, a newborn girl presented with hypertonia, hyperreflexia, tremor, and excessive startle response. nose tap elicited a dramatic head recoil. Her mother had similar symptoms beginning as a child that improved but persisted into adulthood. In addition, several members of mother's family died unexpectedly in infancy. Hypertonia in the newborn period indicates central nervous system dysfunction of several possible causes, most of which are associated with severe cognitive deficits and limited neurological development.- - - - - - - - - - ranking = 0.12744579448445keywords = family, member (Clic here for more details about this article) |
4/42. Radiological and manometric diagnosis of cricopharyngeal dysphagia in a Japanese encephalitis survivor.Japanese encephalitis (JE) is endemic throughout most of the western Pacific region where taiwan is located. About half the survivors are left with neurological damages. We report a 55-year-old male who survived from JE and was left with sequela of parkinsonism and severe swallowing disorder. Later, it was proved to be cricopharyngeal dysphagia (CPD) using esophagogram and manometry, which disclosed involuntary hypertonic and hyperreflexic cricopharyngeal muscle contraction. CPD, a life-threatening neurological sequel of JE, has never been reported in the JE survivors before and possibly results from disseminated lesions over pyramidal and extrapyramidal systems.- - - - - - - - - - ranking = 0.0002448556154246keywords = life (Clic here for more details about this article) |
5/42. Major and minor form of hereditary hyperekplexia.Hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses. Within the disorder two clinical forms can be distinguished. The major form is characterized by continuous generalized stiffness in the first year of life and an exaggerated startle reflex, accompanied by temporary generalized stiffness and falls, whereas in the minor form only excessive startle and hypnic jerks have been described. Mutations in the gene encoding the alpha-1 subunit of the glycine receptor (GLRA1) are responsible for the major form of hyperekplexia but no mutation was detected in patients with the minor form in the large Dutch pedigree originally described by Suhren and colleagues. Here we describe the genetic analysis of the GLRA1 gene of two English families in which both forms of hyperekplexia were present. mutation analysis revealed no genetic defect in the GLRA1 gene in patients carrying either the minor or major forms. This is further evidence that the minor form of hyperekplexia is seldom due to a genetic defect in the GLRA1 gene.- - - - - - - - - - ranking = 0.0002448556154246keywords = life (Clic here for more details about this article) |
6/42. deafness and CMT disease associated with a novel four amino acid deletion in the PMP22 gene.The molecular basis for the clinically distinct entity of deafness with charcot-marie-tooth disease has not been established with certainty. The authors report deafness associated with a demyelinating neuropathy in three individuals of a family in whom a novel four-amino acid deletion in the PMP22 gene was identified. The data and review of literature suggest that in the PMP22 gene, some point mutations and small deletions in the transmembrane domain that are in close proximity to the extracellular component of the protein result in this clinically distinct entity.- - - - - - - - - - ranking = 0.125keywords = family (Clic here for more details about this article) |
7/42. vincristine-induced neuropathy as the initial presentation of charcot-marie-tooth disease in acute lymphoblastic leukemia: a Pediatric Oncology Group study.PURPOSE: After profound peripheral neurotoxicity during induction chemotherapy for acute lymphoblastic leukemia (ALL) in the index patient with Charcot-Marie-Tooth hereditary neuropathy (CMT), study coordinators of the Pediatric Oncology Group (POG) front-line ALL protocols reviewed patient registrations to identify any other patients with possible CMT. The goal was to provide preliminary information about patients with undiagnosed CMT who develop ALL. patients AND methods: Five children with ALL who were enrolled in POG B-precursor or T-cell ALL protocols from 1994 to 1999 subsequently were determined to have CMT hereditary neuropathy. Their clinical presentations and treatment records were reviewed in detail. Records of all patients entered on POG 9201 (lesser-risk ALL) were reviewed to identify all cases of significant vincristine toxicity noted in the first 6 months of treatment. RESULTS: The five identified patients all had substantial peripheral neurotoxicity that required alteration in treatment and/or orthopedic/physical therapy evaluation and follow-up. The POG 9201 review identified 25 of 686 patients (3.6%) with significant peripheral neuropathy. Three of 25 were diagnosed with CMT; the others have had no testing reported. CONCLUSIONS: A family history of CMT or other peripheral neuropathy should be sought at the time of diagnosis of ALL. Testing for CMT should be considered in any child with substantial vincristine-induced peripheral neurotoxicity. Treatment of such patients must be individualized. Testing of all patients with significant peripheral neuropathy would be necessary to determine the percentage of such neuropathy explained by underlying CMT.- - - - - - - - - - ranking = 0.125keywords = family (Clic here for more details about this article) |
8/42. Usher syndrome type III can mimic other types of Usher syndrome.Clinical and genetic characteristics are presented of 2 patients from a Dutch Usher syndrome type III family who have a new homozygous USH3 gene mutation: 149-152delCAGG insTGTCCAAT. One individual (IV:1) is profoundly hearing impaired and has normal vestibular function and retinitis punctata albescens (RPA). The other individual is also profoundly hearing impaired, but has well-developed speech, vestibular areflexia, and retinitis pigmentosa sine pigmento (RPSP). These findings suggest that Usher syndrome type III can be clinically misdiagnosed as either Usher type I or II; that Usher syndrome patients who are profoundly hearing impaired and have normal vestibular function should be tested for USH3 mutations; and that RPA and RPSP can occur as fundoscopic manifestations of pigmentary retinopathy in Usher syndrome.- - - - - - - - - - ranking = 0.125keywords = family (Clic here for more details about this article) |
9/42. Aicardi-Goutieres syndrome: clinical and neuroradiological findings of 10 new cases.AIM: To describe the clinical and neuroimaging findings in new cases with Aicardi-Goutieres syndrome (AGS) from egypt. methods: Ten patients with progressive encephalopathy, bilateral calcification of the basal ganglia and spastic quadriplegia were described. Feeding difficulties, irritability, unexplained episodic fever and acrocyanosis were also observed. They were diagnosed as AGS after excluding possible non-genetic causes (especially TORCH) and because of the high interferon-alpha (IFN-alpha) level in cerebrospinal fluid (CSF) in two children who underwent this specific investigation. RESULTS: Six patients had postnatal microcephaly. putamen was by far the most common site of calcification (nine cases) inside the basal ganglia. Calcifications were extended to the white matter, periventricular and cerebellum in three cases. brain atrophy and/or white matter demyelination were evident in most of the cases. Further, hypogenesis of corpus callosum was detected in two cases; one of them had in addition cerebellar hypoplasia, atrial septal defect (ASD) and horseshoe kidney. To the best of our knowledge, the association of these congenital abnormalities has not been reported before in AGS. Eight families were consanguineous. CONCLUSION: This paper presents variability in both age of onset, clinical picture and neuroimaging findings even in the same family, comprising new congenital abnormalities associated with AGS and subsequently expanding the spectrum of heterogeneity. The observation of familial cases and both affected males and females emphasized the major role of the single gene inheritance.- - - - - - - - - - ranking = 0.125keywords = family (Clic here for more details about this article) |
10/42. hearing loss as the first feature of late-onset axonal CMT disease due to a novel P0 mutation.A Czech family with three individuals carrying a novel mutation, 290 A-->T (Glu97Val), in the myelin protein zero gene (P0) is reported. The two eldest carriers developed progressive sensorineural hearing loss and abnormal pupillary reaction at age 18. These preceded the onset of the classic signs of charcot-marie-tooth disease (CMT) by more than a decade. sural nerve biopsy and nerve conduction studies were compatible with the axonal type of CMT. The authors show that progressive hearing loss can be the first symptom in P0 mutation carriers.- - - - - - - - - - ranking = 0.125keywords = family (Clic here for more details about this article) |
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