Merosin-de®cient congenital muscular dystrophy with mental retardation and cerebellar cysts unlinked to the LAMA2, FCMD and MEB loci Beril Talim a , Ana Ferreiro b , Bru Cormand c , Nicolas Vignier b , Aytekin Oto d , Sa®ye Go Èg Ïu Ès Ë a , Ays Ëenur Cila d , Anna-Elina Lehesjoki c , Helena Pihko e , Pascale Guicheney b , Haluk Topalog Ïlu f, * a Department of Pediatric Pathology, Hacettepe Children's Hospital, Ankara, Turkey b INSERM U523, Institut de Myologie, and IFR 14 `Coeur, Muscle et Vaisseaux', Groupe Hospitalier Pitie Â-Salpe Ãtrie Áre, Paris, France c Department of Medical Genetics, and the Folkha Èlsan Institute of Genetics, University of Helsinki, Helsinki, Finland d Department of Radiology, Hacettepe University, Ankara, Turkey e Department of Child Neurology, Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland f Department of Pediatric Neurology, Hacettepe Children's Hospital, 06100 Ankara, Turkey Received 11 January 2000; received in revised form 16 March 2000; accepted 7 April 2000 Abstract We report a case of congenital muscular dystrophy with secondary merosin de®ciency, structural involvement of the central nervous system and mental retardation in an 8-year-old girl from a consanguineous family. She had early-onset hypotonia, generalized muscle wasting, with weakness especially of the neck muscles, joint contractures, mental retardation and high creatine kinase. Muscle biopsy showed dystrophic changes with partial de®ciency of the laminin a 2 chain. Cranial magnetic resonance imaging revealed multiple small cysts in the cerebellum, without cerebral cortical dysplasia or white matter changes. The laminin a 2 chain (6q2), Fukuyama type congenital muscular dystrophy (9q31±q33) and muscle±eye±brain disease (1p32±p34) loci were all excluded by linkage analysis. We suggest that this case represents a new entity in the nosology of congenital muscular dystrophy. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Congenital muscular dystrophy; Secondary merosin de®ciency; Cerebellar cyst; Mental retardation 1. Introduction Congenital muscular dystrophies (CMD) are a heteroge- neous group of autosomal recessive neuromuscular disor- ders characterized by early-onset muscle weakness, hypotonia, joint contractures and a dystrophic pattern at muscle biopsy. Mental retardation and structural abnormal- ities of the central nervous system occur in some forms, particularly the Fukuyama type CMD (FCMD), muscle± eye±brain disease (MEB) and Walker±Warburg syndrome (WWS). Severe visual failure with structural involvement of the eyes is characteristic for the two latter syndromes. In the two other well-known groups, merosin-positive and mero- sin-de®cient CMD, no major structural brain abnormalities are present although white matter hyperlucency in cranial magnetic resonance imaging (MRI) is a consistent ®nding in merosin-de®cient CMD cases [1±3]. Primary merosin de®ciency is more frequently complete than partial and is associated with a normal intellectual development. It is caused by mutations in the gene encoding the laminin a 2 chain, LAMA2, located on chromosome 6q2 [1,4±6]. Secondary partial merosin de®ciency has been reported in some CMD forms, usually associated with mental retarda- tion. Associated structural brain abnormalities were ®rst reported in FCMD, which is due to mutations in the gene coding for fukutin on 9q31 [7±9], and in MEB, recently localized to 1p32±p34 [10,11]. Four cases with severe mental retardation, microcephaly, brain abnormalities and calf hypertrophy, one of them previously reported by De Stefano et al. [12], have been recently fully characterized as a novel entity by Villanova et al. [13]. This last entity shares several features (mental retardation, secondary mero- sin de®ciency and calf hypertrophy) with the two siblings that we had previously reported, but these cases had no brain abnormalities [14]. A novel and unique CMD case that we had previously presented in a workshop [15] is reported here: an 8 year-old girl with a severe phenotype, mental retardation, cerebellar cysts and partial merosin de®ciency but unlinked to any Neuromuscular Disorders 10 (2000) 548±552 0960-8966/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S0960-8966(00)00140-1 www.elsevier.com/locate/nmd * Corresponding author. Tel.: 190-312-305-1165; fax: 190-312-310- 6262. E-mail address: htopalog@gen.hun.edu.tr (H. Topalog Ïlu).