title: Merosin-positive congenital muscular dystrophy: a large inbred family.
abstract: Large families with congenital muscular dystrophy are rare. We report a clinical, histopathological, immunocytochemical, electrophysiological, radiological and genetic study of 10 cases affected by "pure" CMD belonging to two generations of a large inbred Palestinian family. The disease showed autosomal recessive inheritance. All patients had generalised muscular weakness and hypotonia at birth without arthrogryposis. They had a relatively benign clinical course with stabilisation of the clinical picture at different ages and at variable degrees of severity. The pattern of muscle weakness and wasting was more marked in the proximal upper limb-girdle and trunk muscles. Lower limb muscles were more mildly involved. Serum CK was normal or moderately increased. All patients had normal intelligence, normal computed tomography (CT) scans of the brain and normal somatosensory evoked potentials (SEP). Electromyography (EMG) and muscle biopsy showed morphological changes compatible with muscular dystrophy. Immunocytochemistry for dystrophin, laminin alpha 2 of merosin, and for alpha, beta, gamma sarcoglycans was normal. Linkage analysis excluded all the known loci for CMD, including laminin alpha 2 on chromosome 6q2, the Fukuyama congenital muscular dystrophy locus on 9q3, the integrin alpha 7 locus on chromosome 12q13 and the recently identified locus on 1p35-36. The family we present is clinically and genetically distinct from the already mapped forms of congenital muscular dystrophy. Genetic studies are in progress to localise the gene responsible for this condition.
authors.affiliation: Department of Neurological and Psychiatric Sciences, University of Florence, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Mahjneh
authors.forename: K
authors.initials: K
authors.lastname: Bushby
authors.forename: L
authors.initials: L
authors.lastname: Anderson
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: H
authors.initials: H
authors.lastname: Tolvanen-Mahjneh
authors.forename: R
authors.initials: R
authors.lastname: Bashir
authors.forename: A
authors.initials: A
authors.lastname: Pizzi
authors.forename: M
authors.initials: M
authors.lastname: Brockington
authors.forename: G
authors.initials: G
authors.lastname: Marconi
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D003241:Consanguinity; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007557:Israel / Q000208:ethnology; D007797:Laminin / Q000235:genetics*; D008131:London; D008297:Male; D009123:Muscle Hypotonia / Q000209:etiology; D009132:Muscles / Q000473:pathology*; D009136:Muscular Dystrophies / Q000150:complications / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree
chemical_list: D007797:Laminin