Secondary paroxysmal dyskinesias.

Paroxysmal dyskinesias (PxDs) are involuntary, episodic movements that include paroxysmal kinesigenic (PKD), paroxysmal nonkinesigenic (PNKD), and paroxysmal hypnogenic (PHD) varieties. Although most PxDs are primary (idiopathic or genetic), we found 17 of our 76 patients with PxD (22%) to have an identifiable cause for their PxD (10 men; mean age, 41.4 years). Causes included peripheral trauma (in three patients), vascular lesions (in four), central trauma (in four), kernicterus (in two), multiple sclerosis (in one), cytomegalovirus encephalitis (in one), meningovascular syphilis (in one), and migraine (in one). The latency from insult to symptom onset ranged from days (trauma) to 18 years (kernicterus), with a mean of 3 years. Nine patients had PNKD, two had PKD, five had mixed PKD/PNKD, and one had PHD. Hemidystonia was the most common expression of the paroxysmal movement disorder, present in 11 patients. Both of the patients with PKD had symptom durations of <5 minutes. Symptom duration ranged from 10 seconds to 15 days for PNKD and from 5 minutes to 45 minutes for mixed PKD/PNKD. There were no uniformly effective therapies, but anticonvulsant drugs, clonazepam, and botulinum toxin injections were the most beneficial. Awareness of the variable phenomenology and the spectrum of causes associated with secondary PxD will allow for more timely diagnosis and early intervention.     

Charcot-Marie-Tooth neuropathy type 1A combined with Duchenne muscular dystrophy

We report a 24-year-old male with an unusual combination of two inherited neuromuscular disorders – Charcot-Marie-Tooth (CMT) disease type 1A and Duchenne muscular dystrophy (DMD). A phenotypic presentation of this patient included features of both these disorders. Nerve conduction studies revealed demyelinating peripheral neuropathy. Electromyography showed a profound myogenic pattern. The serum creatine kinase level was highly elevated. Muscle biopsy revealed a dystrophic picture with deficient dystrophin immunostaining. CMT1A duplication on chromosome 17p11.2 was found. The frame-shift mutation c.3609–3612delTAAAinsCTT (p.K1204LfsX11) was detected in the dystrophin gene by analysing mRNA isolated from the muscle tissue. The patient inherited both these mutations from his mother. The combination of CMT1A and DMD has not been reported as yet.     

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p-HSP) and complicated forms (c-HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p-HSP ( n  = 21) and c-HSP type ( n  = 12), and 30 age-matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer-independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group ( P  < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c-HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI-based brain volume quantification, is a biological marker in HSP subtypes.     

中国人HNPCC家系的临床特征及M3胆碱能受体基因(A)8区突变检测

目的:分析中国人遗传性非息肉病性大肠癌(HNPCC)家系的临床特征并检测这些家系中M3胆碱能受体基因(A)8区的突变情况.方法:根据2003年4月杭州会议制定的中国人HNPCC家系标准收集HNPCC家系共15个,分析其临床特征;提取先证者的外周血基因组DNA,PCR扩增M3胆碱能受体基因第8外显子中一段长153 bp,包含有微卫星位点(A)8的基因片段,直接进行DNA测序.结果:15个家系共有恶性肿瘤患者55例,其中大肠癌患者41例,平均每个家系发生大肠癌2.73例,73%的大肠癌患者发病年龄<50岁,51%的病灶位于近端结肠,40%发生在直肠肛门,同时和异时多原发大肠癌总发生率为12%,2/3的家系属于Lynch Ⅱ型,共发生肠外恶性肿瘤14例(18个),其中胃癌最常见.15例先证者外周血中无1例检测到M3胆碱能受体基因(A)8区的突变.结论:M3胆碱能受体基因与中国人群中HPNCC的发病可能无密切关系.中国人HNPCC家系标准应在临床工作中推广应用,并进一步验证其合理性和科学性.     

Novel C59T leader peptide mutation in the MPZ gene associated with late-onset, axonal, sensorimotor polyneuropathy

The objective of this study was to report a novel exon-1 mutation in the myelin protein zero (MPZ) gene, resulting in axonal Charcot–Marie–Tooth neuropathy with recurrent hyper-CK-emia. In a 64-year-old woman slowly progressive distal lower limb weakness, muscle cramps in the lower limb muscles, and stocking-type numbness had developed from the age of 61. Neurologic examination revealed discrete hip flexor weakness, weakness for foot extension, diffuse wasting of the distal lower limb muscles, reduced patella tendon reflexes, and absent Achilles tendon reflexes. There was recurrently elevated creatine kinase with a maximum of 607 U/l ( n , <145 U/l). Stimulation of the peroneal and tibial nerves did not evoke a muscular response. Electromyography was neurogenic. Biopsy of the right sural nerve showed diffuse axonal degeneration and loss of axons of all diameters. Muscle biopsy showed increased fiber-size variability, angulated fibers, internalized nuclei, accumulations of nuclei, grouped atrophic muscle fibers, and fiber splitting. Molecular genetic analysis by PCR and direct nucleotide sequencing revealed the heterozygous C59T exon-1 MPZ gene mutation, resulting in the amino acid exchange S20F of the MPZ signal protein domain (leader peptide). The novel C59T mutation in the leader peptide of the MPZ gene is pathogenic and manifests as severe, late-onset, axonal, symmetric sensorimotor polyneuropathy (CMT2) and hyper-CK-emia.     

Lymphangiosarcoma in late-onset hereditary lymphedema: Case report and nosological implications

Hereditary lymphedemas that are not associated with other malformations usually affect the lower limbs and are inherited in an autosomal dominant fashion. These non-syndromic hereditary lymphedemas are categorized by their age of onset, being either congenital (Milroy disease) or having an onset in childhood or around puberty (Meige disease). We describe a family in which three individuals in three generations had unusually late onset of lym-phedema in their mid-twenties or thirties. The proband additionally developed a very rare lymphangiosarcoma. This tumor, usually associated with post-mastectomy lym-phedema, has not been described in late-onset hereditary lymphedema. Because of an unusually high incidence of multiple primary tumors in association with lymphangiosarcoma in the literature (approximately 10%) and the proband's own familial cancer background, we speculate that an inherited predisposition to malignancy may underlie the development of lymphedema-associated lymphangiosarcoma. © 1995 Wiley-Liss, Inc.     

Hereditary Hypertriglyceridemic Rat: A New Animal Model of Metabolic Alterations in Hypertension

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerrance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na⁺ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.