title: Merosin-positive congenital muscular dystrophy with mental retardation, microcephaly and central nervous system abnormalities unlinked to the Fukuyama muscular dystrophy and muscular-eye-brain loci: report of three siblings.
abstract: Classical merosin (2 laminin)-positive congenital muscular dystrophy is a heterogeneous subgroup of disorders; a few cases characterized by severe mental retardation, brain involvement and no ocular abnormalities were called Fukuyama-like congenital muscular dystrophy. We report a family of healthy non-consanguineous parents, with four affected siblings, of which one died at the age of 7 months due to an intercurrent illness, who presented congenital hypotonia, severe mental retardation, microcephaly, delayed psychomotor development, generalized muscular wasting and weakness with mild facial involvement, calf pseudohypertrophy, joint contractures and areflexia. Muscle biopsy disclosed severe muscular dystrophy. Immunostaining for laminin 2 80 kDa and clone Mer3/22B2 monoclonal antibodies, 1 and 1 chain was preserved. Magnetic resonance imaging findings were consistent with pontocerebellar hypoplasia, bilateral opercular abnormalities and focal cortical dysplasia as well as minute periventricular white matter changes. Clusters of small T2-weighted focal hyperintensities in both cerebellar hemispheres consistent with cysts were observed in two of the three siblings studied with magnetic resonance imaging. Ophthalmologic and cardiologic examination was normal. Haplotype analysis using microsatellite markers excluded the Fukuyama congenital muscular dystrophy, LAMA2 and muscle-eye-brain disease loci. Thus, a wider spectrum of phenotypes, gene defects and protein deficiencies might be involved in congenital muscular dystrophy with brain abnormalities.
authors.affiliation: J.P. Garrahan National Paediatric Hospital, Buenos Aires, Argentina.
authors.forename: V
authors.initials: V
authors.lastname: Ruggieri
authors.forename: F
authors.initials: F
authors.lastname: Lubieniecki
authors.forename: F
authors.initials: F
authors.lastname: Meli
authors.forename: D
authors.initials: D
authors.lastname: Diaz
authors.forename: E
authors.initials: E
authors.lastname: Ferragut
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: M
authors.initials: M
authors.lastname: Brockington
authors.forename: F
authors.initials: F
authors.lastname: Muntoni
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuyama
authors.forename: A L
authors.initials: AL
authors.lastname: Taratuto
mesh_terms: D001706:Biopsy; D001921:Brain / Q000002:abnormalities; D002648:Child; D019066:Facies; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D007797:Laminin / Q000032:analysis*; D008297:Male; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000737:chemistry / Q000473:pathology; D009136:Muscular Dystrophies / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D009679:Nuclear Family; D010375:Pedigree
chemical_list: D007797:Laminin