Autosomal dominant temporal lobe epilepsy in a Japanese family

We described autosomal dominant familial temporal lobe epilepsy in a Japanese family in which three individuals (one man and his two children) were affected. Their seizures commonly consisted of auditory symptoms and infrequent nocturnal generalized seizures. Repeated EEGs did not provide confirmative epileptiform discharges, but cranial MRI in one patient showed mild left hippocampal atrophy, and decreased glucose metabolism in the left temporal area was demonstrated by 18F-deoxyglucose positron emission tomography (FDG-PET). A confirmative diagnosis in one of the patients by FDG-PET was helpful for diagnosis in other patients in the same family. Seizure onset was adolescent commonly among the three patients, but better seizure control was achieved in the father as compared with the two children.     

Autosomal dominant congenital Horner''s syndrome in a Dutch family.

A Dutch family is reported with congenital Horner's syndrome in five cases spanning five generations, with symptoms of varying degree but mainly ptosis and meiosis. Heterochromia iridium, anhidrosis, and enophthalmos were not present. The site of the lesion may be in the region between Gasser's ganglion and the short vertical segment of the internal carotid artery near the siphon. There are only four previous reports showing autosomal dominant inheritance of congenital Horner's syndrome.     

Autosomal dominant dopa-responsive parkinsonism in a multigenerational Swiss family

AIM: To describe a large family with autosomal dominant parkinsonism. BACKGROUND: Seven genes are directly implicated in autosomally inherited parkinsonism. However, there are several multigenerational large families known with no identifiable mutation. MATERIAL AND METHODS: Family members were evaluated clinically, by history and chart review. Genetic investigation included SCA2, SCA3, UCHL1, SNCA, LRRK2, PINK1, PRKN, PGRN, FMR1 premutation, and MAPT. The proband underwent brain fluorodopa PET (FD-PET) scan, and one autopsy was available. RESULTS: Eleven patients had a diagnosis of Parkinson's disease (PD), nine women. Mean age of onset was 52 with tremor-predominant dopa-responsive parkinsonism. Disease progression was slow but severe motor fluctuations occurred. One patient required subthalamic nucleus deep-brain stimulation with a good motor outcome. One patient had mental retardation, schizophrenia and became demented, and another patient was demented. Three patients and also two unaffected subjects had mild learning difficulties. All genetic tests yielded negative results. FD-PET showed marked asymmetric striatal tracer uptake deficiency, consistent with PD. Pathological examination demonstrated no Lewy bodies and immunostaining was negative for alpha-synuclein. CONCLUSION: Apart from a younger age of onset and a female predominance, the phenotype was indistinguishable from sporadic tremor-predominant PD, including FD-PET scan results. As known genetic causes of autosomal dominant PD were excluded, this family harbors a novel genetic defect.     

Autosomal dominant Lewy body parkinsonism in a four-generation family

We report a family with autosomal dominant parkinsonism. The propositus developed parkinsonism at a relatively young age (45 years) and came to autopsy after a 6-year illness. She had typical features of Parkinson's disease except for an absence of rest tremor, although this was present in other family members. A diagnosis of Lewy body parkinsonism was confirmed by neuropathological examination. Additional pathological features included the presence of cortical Lewy bodies and anti-ubiquitin-positive neurites in the cornu Ammonis 2 and 3 (CA2-3) region of the hippocampus. This kindred is similar both clinically and pathologically to a few previously reported pedigrees, further strengthening recent evidence of a genetic etiology of some forms of Parkinson's disease.     

Autosomal dominant motor system degeneration in a black family

Autosomal dominant motor system degeneration has been described primarily in Portuguese families from the Azorean Islands. The symptoms include various combinations of ataxia, pyramidal and extrapyramidal signs, appendicular dystonias, tics, ophthalmoplegias, and peripheral neuropathies with amyotrophy. One non-Portuguese, non-Azorean black family has been described previously; this report describes a second such family affected by autosomal dominant motor system degeneration.     

Autosomal dominant burning feet syndrome

Familial burning feet syndrome inherited as an autosomal dominant trait has been described in only one family. Due to an associated sensory neuropathy the autosomal dominant burning feet syndrome was suggested to represent a variant form of hereditary sensory and autonomic neuropathy type I (HSAN I). Clinical, histopathological, and molecular genetic studies were performed in a large German kindred with autosomal dominant burning feet syndrome. The autosomal dominant burning feet syndrome was associated with a neuropathy predominantly affecting small unmyelinated nerve fibres. Linkage to the HSAN I locus on chromosome 9q22 and to the Charcot-Marie-Tooth disease type 2B (CMT 2B) locus on chromosome 3q13-q22 was excluded. The autosomal dominant burning feet syndrome is neither allelic to HSAN I nor to CMT 2B and thus represents a distinct genetic entity.     

Autosomal dominant episodic ataxia: a heterogeneous syndrome

We describe six kindreds with autosomal dominant episodic ataxia, apparently representing three distinct syndromes. Four kindreds were characterized by episodic ataxia and response to acetazolamide, and in three, interictal nystagmus. One kindred was characterized by paroxysmal ataxia and in one member, paroxysmal choreoathetosis. The last kindred had brief attacks of ataxia and interictal neuromyotonia. The age of onset and severity of the disorder varied within each kindred. These kindreds illustrate the heterogeneity of episodic ataxia as well as the variable expressivity within each kindred.     

Autosomal dominant myoclonus-dystonia and Tourette syndrome in a family without linkage to the SGCE gene.

The objective of this study was to report clinical details and results of genetic testing for mutations in the epsilon-sarcoglycan (SGCE) gene, the Slit and Trk-like 1 (SLITRK1) gene and for linkage to the DYT15, DYT1, and DRD2 gene loci in a family with autosomal dominant myoclonus-dystonia (M-D) and Gilles de la Tourette syndrome (GTS). Fourteen family members, from three generations, underwent a detailed clinical assessment and donated DNA samples. The SGCE and the SLITRK1 gene were sequenced and investigated by gene dosage analysis in selected family members. Linkage to the SGCE, DYT15, DYT1, DRD2, and SLITRK1 loci was also tested. Results: We included three healthy and 11 affected family members with M-D (n = 3), dystonia alone (n = 2), GTS (n = 1), tics (n = 1) or a combination of these with obsessive compulsive disorder (OCD) (M-D + OCD: n = 2; dystonia+OCD: n = 1; M-D + GTS + OCD: n = 1). There was no linkage to the SGCE, DYT15, DYT1 or DRD2 loci. No changes were found in the SLITRK1 gene. The presence of both M-D and GTS in one family, in which all known M-D loci and a recently discovered GTS locus were excluded, suggests a novel susceptibility gene for both M-D and GTS.     

Autosomal dominant essential tremor: a novel family with anticipation

Essential tremor (ET) is a common progressive movement disorder characterized by a clear genetic predisposition. In the last years, many efforts have been done to map susceptibility loci for ET. Here, we report a clinical and genetic study of a family with ET showing autosomal dominant inheritance and anticipation over three generations. The family has five affected members and exhibits a remarkable anticipation of age at onset of the disease along the generations. We excluded linkage to any of the three loci previously mapped in autosomal dominant ET families. Our data suggest the existence of an additional locus in which a repeat expansion is the possible genetic defect underlying ET.     

Autosomal dominant centronuclear myopathy: Report of a new family with clinical features simulating facioscapulohumeral syndrome

The centronuclear myopathies are a clinically and genetically heterogeneous group of disorders which share similar histological features on muscle biopsy. The familial cases have been classified genetically as X-linked or autosomal in inheritance. The autosomal forms usually have a later onset and milder course as compared to the X-linked form. Thirteen families with autosomal dominant centronuclear myopathy have been previously described. We describe an additional family with unique clinical features which initially suggested a facioscapulohumeral syndrome. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20:1194–1196, 1997     

Autosomal dominant GTP-CH deficiency presenting as a dopa-responsive myoclonus-dystonia syndrome

The authors report a kindred in which GTP-CH deficiency resulted in a myoclonus-dystonia syndrome. The proband, a 17-year-old boy, presented with early-onset myoclonus and later, dystonia and bradykinesia. Blood prolactin was increased and CSF homovanillic acid, 5-hydroxyindoleacetic acid, and biopterin were all reduced. L-Dopa/carbidopa administration resulted in clinical improvement. In the paternal branch, the grandfather and three relatives had myoclonus-dystonia and resting or postural tremor of limbs. The authors found a missense mutation in the exon 6 of GCH-1 gene (K224R).     

Autosomal dominant syndrome with strokelike episodes and leukoencephalopathy

BACKGROUND AND PURPOSE: We conducted a prospective survey of a family presenting a new syndrome characterized mainly by recurrent strokelike episodes and neuroimaging evidence of leukoencephalopathy. SUMMARY OF REPORT: Forty-five members of a single family were studied clinically and with magnetic resonance imaging. Nine had strokelike episodes, including transient ischemic attacks, and minor or major strokes starting between the fourth and sixth decades, with neuroimaging evidence of small, deep infarcts and a widespread white matter disorder. Other symptoms included migraine (three), dementia (two), epilepsy (one), and hearing loss (one). In some patients, we found various immunologic anomalies and muscular lipidosis without ragged-red fibers. Eight other family members were clinically normal, but had identical neuroimaging signs of leukoencephalopathy. No abnormality was detected in the 28 other members of the family examined. Extensive investigations failed to reveal any known cause of cerebral ischemia. CONCLUSIONS: There appears to be a new syndrome in this family that is characterized by recurrent subcortical strokelike episodes, leukoencephalopathy, immunologic anomalies, muscular lipidosis, and an autosomal dominant pattern of transmission.     

常染色体显性遗传性进行性眼外肌瘫痪一个家系的症状发展规律

目的报道一个常染色体显性遗传性进行性眼外肌瘫痪家系的临床症状发展规律。方法分析了该家系连续5代共20例患者的症状发展过程，并对先证者和其他4例患者分别进行了肌肉病理和肌电图检查。结果先证者为57岁女性，30岁出现双眼睑下垂，35岁出现眼外肌瘫痪，37岁出现四肢力弱，47岁出现延髓部症状，有时出现心悸。20例患者发病年龄在26—33岁之间，男女均累及，均以双眼睑下垂为首发症状；在35—45岁之间15例中12例出现眼球活动障碍，14例出现四肢无力；在44—60岁之间9例全部出现面肌或咀嚼肌无力，其中8例出现吞咽障碍；50岁后7例中4例出现心脏损害并导致死亡。肌电图检查均提示骨骼肌存在肌源性损害。肌肉活检发现不整红边纤维、细胞色素氧化酶阴性肌纤维和琥珀酸脱氢酶染色的不整蓝边纤维。结论常染色体显性遗传性进行性眼外肌瘫痪的临床表现从眼外肌开始，逐渐累及四肢肌肉，而后损害面部和延髓部肌肉，晚期出现心脏损害并导致部分患者死亡。症状的发展规律提示应当在疾病后期关注其心脏损害的表现。     

Autosomal dominant Emery-Dreifuss muscular dystrophy: a new family with late diagnosis.

Emery-Dreifuss muscular dystrophy is characterized by the clinical triad of early onset contractures of elbows, Achilles tendons and spine, wasting and weakness with a predominantly humero-peroneal distribution and life-threatening cardiac conduction defects and/or cardiomyopathy. Two main types of inheritance have been described: the X-linked form is caused by mutations in the STA gene on locus Xq28 and the gene for the autosomal dominant form (LMNA gene) has been localized on chromosome 1q11-q23. Recently, mutations in this LMNA gene have been also found to be responsible for the less frequent autosomal recessive form of the disease. Although all forms share a similar clinical presentation, some differences appear to exist between them as has been described recently in a large number of patients. We present the first documented Spanish family genetically confirmed to have autosomal dominant Emery-Dreifuss muscular dystrophy. Clinical, pathological and genetic data are described. We emphasize the difficulties in diagnosis, especially in sporadic cases or young patients in whom the clinical picture is not completely established.     

Autosomal dominant partial epilepsy with auditory features: description of a new family

PURPOSE: To report the clinical and genetic study of a new family with autosomal dominant partial epilepsy with auditory features (ADPEAF). METHODS: All the living affected members underwent a full clinical, neurophysiological, and magnetic resonance imaging (MRI) study. Genetic analysis was performed by typing their DNA with seven microsatellite markers previously found to cosegregate with ADPEAF on chromosome 10q24. RESULTS: The three living affected members had a childhood onset of rare and drug-responsive tonic-clonic seizures constantly preceded by a humming sensation. Routine and sleep electroencephalograms revealed rare and inconstant focal abnormalities over both temporal regions. MRI detected atrophy with increased T2 signal in the subcortical lateral portion of the right temporal lobe in one case. Analysis of 10q24 polymorphic alleles showed the same haplotype in all three affected members but different alleles in unaffected individuals. CONCLUSIONS: ADPEAF is a distinct condition with homogeneous clinical features. Genetic findings are consistent with linkage of ADPEAF to chromosome 10q24.     

Autosomal dominant glut-1 deficiency syndrome and familial epilepsy

Glut-1 deficiency syndrome was first described in 1991 as a sporadic clinical condition, later shown to be the result of haploinsufficiency. We now report a family with Glut-1 deficiency syndrome affecting 5 members over 3 generations. The syndrome behaves as an autosomal dominant condition. Affected family members manifested mild to severe seizures, developmental delay, ataxia, hypoglycorrhachia, and decreased erythrocyte 3-O-methyl-D-glucose uptake. Seizure frequency and severity were aggravated by fasting, and responded to a carbohydrate load. Glut-1 immunoreactivity in erythrocyte membranes was normal. A heterozygous R126H missense mutation was identified in the 3 patients available for testing, 2 brothers (Generation 3) and their mother (Generation 2). The sister and her father were clinically and genotypically normal. In vitro mutagenesis studies in Xenopus laevis oocytes demonstrated significant decreases in the transport of 3-O-methyl-D-glucose and dehydroascorbic acid. Xenopus oocyte membranes expressed high amounts of the R126H mutant Glut-1. Kinetic analysis indicated that replacement of arginine-126 by histidine in the mutant Glut-1 resulted in a lower Vmax. These studies demonstrate the pathogenicity of the R126H missense mutation and transmission of Glut-1 deficiency syndrome as an autosomal dominant trait.     

Autosomal dominant nocturnal frontal lobe epilepsy: the syndrome]

The identification of the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in 1994 was rapidly followed by that of other familial forms of non lesional partial epilepsies (familial temporal lobe epilepsy, autosomal dominant partial epilepsy with variable foci). Since then around forty families with ADNFLE have been described, most of them having only 3 or 4 affected individuals. The epilepsy usually begins during childhood (mean age at onset: 11 years). The seizures mainly consist of motor elements which can be dystonic, tonic or hyperkinetic (bipedal automatisms, pelvic thrashing movements...), often preceded by a non specific aura. They are brief and frequent, taking place at night, in clusters. Some patients also present some diurnal seizures. One third of the patients report the occurrence of rare secondarily generalized tonic-clonic seizures. There is a large intra-familial variability as to age of onset, intensity of the manifestations and the course of the epilepsy. During the period of highest frequency of seizures, some patients may present moderate neuropsychological disturbances concordant with frontal dysfunctioning, or transitory behavioral disorders. The seizures often subside with age and may even disappear at adulthood. The most effective antiepileptic drug is carbamazepine, however pharmacoresistance is seen in 20 to 30 p. 100 of the cases. Interictal EEG shows non specific epileptiform anomalies with a frontal predominance, often seen solely on sleep recording, in more than half of all patients. Ictal EEG does not always give evidence of definite ictal discharges. The clinical heterogeneity of ADNFLE as it is especially observed in very variable types of auras which are non localizing, aside form the EEG's own limits, makes it difficult to localize the primary epileptic focus with certainty in the frontal lobe in all cases. In all, the clinical and electrical spectrum of ADNFLE is large, and the topographical identification of these familial frontal lobe epilepsies sets the same problems as for sporadic, classical cryptogenic frontal lobe epilepsies.     

Autosomal dominant Emery-Dreifuss syndrome: Evidence of a neurogenic variant of the disease

Summary The first German family with autosomal dominant Emery-Dreifuss syndrome (EDS) is described, with electrophysiologic and myopathologic results providing evidence of a primary neurogenic disease. According to classification of the scapulo peroneal syndrome without cardiomyopathy, we conclude that there are two variants of EDS: one myopathic, the other neurogenic in origin. Therefore, the term Emery-Dreifuss muscular dystrophy should be avoided. Instead, each case of EDS should be classified as myopathic or neurogenic with X chromosome recessive or autosomal dominant inheritance.The results of this study were presented in part at the 8th international congress of electromyography and related neurophysiology, Sorrento, Italy 1987