432 Abstracts CMP.10 Congenital muscular dystrophy and cerebellar hypoplasia. An original cerebro-muscular syndrome B. Echenne ~ F. Riviera'b, M. Tardieu b, M. Brive", D. Mornetc "Service de Neuropediatrie, H@ital Saint-Eloi, 34295 Montpellier, France, ~'Service de Neuropediatrie, H@ital de Bicetre, Kremlin Bicetre, Paris, France, Clnserm U 300, Montpellier, France Two siblings and two other unrelated patients exhibited congenital muscular dystrophy (CMD) with typical dystrophic changes and normal immunocytochemical staining on muscle biopsy, including merosin, dys- trophin and dystrophin-related proteins. They showed marked ataxia sec- ondary to cerebellar hypoplasia, with normal cerebral white matter and cortical organisation on neuroimaging. In our patients, as in the four other patients already published in the literature, the cerebellar involvement is the only CNS manifestation; the clinical condition remains stable, with no deterioration. The CMD has been reported as benign in all these cases, in whom the motor disability seems to be related more to the cerebellar dysfunction than to the muscular disease. We believe that these patients correspond to a clinico-pathological condition which differs from the cur- rent classifications of CMD. As in the other forms of CMD, the familial occurrence of CMD associated with cerebellar hypoplasia in 4 out of 8 published cases suggests an autosomal recessive inheritance pattern. CMP.11 Autosomal dominant type of congenital muscular dystrophy F.JM. Gabre~ls, Q.H. Leyten, H.J. ter Laak, W.O. Renier, B. Ceulemans, J.J. Martin Institute of Neurology, University of Nijmegen, The Netherlands and Department of Neurology, UniversiO, of Antwerp, Belgium We report two unrelated families with congenital muscular dystrophy (CMD) in two generations. In general, an autosomal recessive mode of inheritance is accepted for CMD. Inheritance in our families is most likely autosomal dominant. In 1980, Kalyanaraman et at. reported a family with an autosomal dominant CMD and a possible involvement of the central nervous system. Our patients (father + daughter and father + son + daugh- ter) suffered from CMD without central nervous system involvement. The histological findings, especially some mitochondrial abnormalities in the muscle biopsies of the fathers were remarkable. Keywords: Congenital muscular dystrophy; Autosomal dominant inheri- tance; Mitochondrial abnormalities CMP.12 X-linked vacuolated myopathy: a new family M. Coqueta, D. Fontanb "Departments of' Neuropathology and bNeuropediatry, H@ital Pellegrin, Place Amelie Raba-Leon, 33076 Bordeaux, France in 1988 Kalimo et al. (Ann Neurol 1988;23:258-265) described an X- linked myopathy characterised by weakness of the proximal limb muscles without cardiac involvement and by a very slow progression. Muscle biopsy showed excessive autophagy. Two other families have been reported (Villanova et al., Ann Neurol 1995;37:637-645 and Chabrol et al., colloque AFMI996). Case report. A 17 year-old boy had had difficulty running and climbing stairs since the age of 12 years. He had atrophy of the thigh muscles. No cardiac involvement was observed and intelligence was normal. EMG showed myopathic changes. The serum CK concentra- tion was elevated. A muscle biopsy was performed on the deltoid. His brother aged 12 years was just beginning to have difficulties in climbing stairs. His mother aged 36 years had no clinical muscle symptoms but accepted a quadriceps biopsy. Muscle biopsies. In the deltoid, 80% of muscle fibres were vacuolated. No necrotic fibres were observed. There was no glycogen storage. Antidystrophin and antilaminin antibodies stained the margin of all vacuoles. HLA class 1 was expressed both by the sarcolcmma of the muscle fibres and the margin of the vacuoles. The vacuoles were often in continuity with the sarcolemma. Ultrastmctural study showed numerous membrane-bound vacuoles with round dense granules of variable size. In 90% of muscle fibres the same material was observed all around the fibres in numerous small invaginations of the sarcolemma and beneath the basal lamina. In the quadriceps biopsy, 0.5% of the muscle fibres were vacuolated and showed the same immu- nological and ultrastructural pattern as in the son. Discussion. Leboutin et al. (Ann Neurol 1997;41:117-112) showed in the family reported by Villanova a strong deposition of membrane attack complex and calcium accumulation on the damaged cell surface membrane. In their opinion, 'calcium accumulation on sarcolemma could be secondary to membrane attack complex deposition on the cell surface'. In our case, the presence of a few lesions in the mother indicated that she was an asymptomatic carrier. Keywords: X-linked myopathy; Vacuoles GENERAL POSTER 1A: MUSCULAR DYSTROPHY I (CMD-DMD) GP1A.1 Protection of extraocular muscle in murine merosin-deficient conge- nital muscular.dystrophy correlates with normal cation homeostasis J.D. Porter, P. Karathanasis Departments" of Anatomy, Neurobiology and Ophthalmology, UniversiO, of Kentucky, USA The unique extraocular muscle (EOM) phenotype may be mechanistic in an often atypical response to neuromuscular disease, including sparing in dystrophinopathy and merosin-deficient congenital muscular dystrophy (CMD). We addressed cation homeostasis as a potential protective mechanism in murine (129/ReJ Lama-2 ay) merosin-deficient CMD. In contrast to the hindlimb, EOM lacked histologic signs of atrophy/degen- eration/regeneration. By atomic absorption spectroscopy, EOM lacked the increase in [Ca 2+1 that characterized hindlimb muscles. There was a cor- responding 2x increase in hindlimb total Ca2+-ATPase activity, while activity was unchanged in EOM. These data correlate the pattern of pathol- ogy in CMD with Ca 2+ regulation. ELISA of SERCA isoforms showed a reduction in SERCA1 in both muscle groups. SERCA2 was elevated in the hindlimb only, reflecting the principal isoform of regenerating muscle. Finally, there was a 2x increase in Na+/Ca 2+ exchanger protein in hin- dlimb, and a trend toward an increase in EOM. Together with our obser- vations of Na + loading and ATPase activity, this finding supports the increased extracellular export of Ca 2+ in dystrophic mice, via the Na+/ Ca 2+ exchanger and plasma membrane Ca2+-ATPase, in the hindlimb. The sarcolemmal Ca 2+ transporters appear to be less involved in EOM. Taken together, our data support a correlation between the presence/ absence of alterations in cation homeostasis and muscle group-specific pathology in CMD. This does not, however, contribute to the debate as to whether elevated [Ca2+]i is a 1 ° or 2° event in CMD pathogenesis. The relative absence of changes in Ca 2÷ homeostasis lends support to the hypothesis that EOM sparing is mediated by a mechanism other than the constitutively high Ca 2+ scavenging capacity of this muscle group. Sup- ported by NIH and MDA. Keywords: Congenital muscular dystrophy; Extraocular muscle; Cation homeostasis GP1A.2 Long-term prognosis in congenital muscular dystrophy without men- tal retardation Helena Pihko, Tuula Louhimo, Mfirta Donner Division of Paediatric Neurology, Hospital for Children and Adolescents, UniversiO, of Helsinki, 00290 Helsinki. Finland We present follow-up data of 32 patients with congenital muscular dystrophy diagnosed at the Children's Hospital, University of Helsinki during the years 1965-1990. The patients had generalised muscle weak- ness and hypotonia at birth or from the first months of life, dystrophic