P.P.1 05 Magnetic resonance imaging findings in a newborn with merosin-deficient congenital muscular dystrophy

Abstracts / Neuromuscular Disorders 16 (2006) 644–726 belonging to 32 families have been studied. Consanguinity rate was very high (70%). A group of 18 patients, from 16 families (47%), was classified as MDC1A or merosin-deficient CMD. Fifteen patients, with a total absence of laminin alpha2, never achieved ambulation, whereas 3 patients with partial absence of this protein could walk. Six cases belonging to 3 families had Ullrich CMD (UCMD). Two new mutations in COL6A1 and COL6A2 were identified in two families. Four MDC1C patients (3 families) had clinical picture similar to MDC1A. Three patients were harboring two new homozygous mutations in the FKRP gene.Two unrelated RSMD patients were observed. Only one of them was linked to SEPN1 gene. One patient had a CMD with a head lag. Mental development and brain MRI were normal. Two sisters had a CMD with an Emery-Dreifuss phenotype with elbows and ankles contractures. All the known CMD loci and LMNA gene were excluded. Two brothers had a MDC1A phenotype without any mutation of LAMA2, FKRP, POMT1, FCMD and Large genes. Three patients had CMD with neuronal migration abnormalities: 2 patients had Fukuyama CMD-like phenotype, the 3rd patient had MEB-like phenotype. They all had alpha-dystroglycan deficit on muscle biopsy. In conclusion this study had contributed to the international effort for the CMD better knowledge. Two new mutations were found in Ullrich CMD and two other new mutations in MDC1C. Moreover in four different CMD phenotypes, all the known CMD loci were excluded, showing that new genes remain to be discovered. doi:10.1016/j.nmd.2006.05.072

P.P.1 04 Algerian FKRP mutations causing MDC1C congenital muscular dystrophy with mental retardation S. Makri 1,*, P. Richard 2, S. Maugenre 3, N. Terki 4, S. QuijanoRoy 5, S. Assami 6, N.B. Romero 3, M. Ait-Kaci 1, P. Guicheney 3 1 Service de Neurologie, Etablissement Hospitalier Spe´cialise´ Ali Ait Idir, Algers, Algeria; 2 Unite´ de Cardio-myoge´ne´tique mole´culaire et cellulaire, Groupe Hospitalier, Pitie´ Salpeˆtrie`re, Paris, France; 3 Institut National de la Sante´ et de la Recherche Me´dicale, U582, Institut de Myologie, IFR 14, Paris, France; 4 Laboratoire d’anatomopathologie du, Centre Pierre et Marie Curie, CHU Mustapha, Algers, Algeria; 5 Service de Pe´diatrie, Hoˆpital Raymond Poincare´, Garches, France; 6 Service de Neurologie, CHU Mustapha, Algers, Algeria Fukutin-related-protein (FKRP) gene mutations cause a very wide spectrum of conditions ranging from the most severe forms of congenital muscular dystrophy (Walker-Warburg syndrome, MDC1C) to LGMD2I. These entities are associated with an abnormal glycolysation of the alpha-dystroglycan. Three unrelated patients had characteristic features of MDCIC with moderate mental retardation. They all presented with neonatal hypotonia, delay of motor development, facial weakness, proximal weakness of the upper limbs, wasting of the shoulder girdle, progressive contractures and leg hypertrophy. Elevated serum creatine kinase and dystrophic changes with virtual absence of glycosylated alpha-dystroglycan in muscle biopsy were found. Molecular genetic analyses identified two novel homozygous missense FKRP mutations. The first mutation c.1213G > T (Val 405Leu) in case1 leads to a moderate muscular phenotype at the 6 years but brain IRM revealed severe posterior fossa malformation including multiple cerebellar cysts, marked vermis hypoplasia, enlarged cisterna magma, mild pons hypoplasia, and abnormal white matter signal in the periventricular region and in the cerebellum, which is unusual. The second mutation a transverion c.329G > C (Arg110Pro) was found in two children. In one case, it leads to a mild phenotype with walking capacity at the age of 4 years and a moderate unilateral left vermis hypoplasia, few cerebellar cysts, mild pons hypoplasia and left temporal atrophy. The other child aged of 7 years had a severe muscular phenotype with convergent strabismus and severe myopia but normal brain imaging.

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In conclusion, we identified 2 FKRP mutations in three patients originating from Algeria. These mutations are different from those already described in Tunisia and Morocco (mutation 1363C > A, A455D). Some phenotypic variability was observed between the two children harbouring the same homozygous mutation. doi:10.1016/j.nmd.2006.05.073

P.P.1 05 Magnetic resonance imaging findings in a newborn with merosin-deficient congenital muscular dystrophy G. Haliloglu 1, K. Karli Oguz 2, D. Orhan 3, M. Yurdakok 4, H. Topaloglu 1,* 1 Hacettepe University Faculty of Medicine, Department of Pediatric Neurology, Ankara, Turkey; 2 Hacettepe University Faculty of Medicine, Department of Radiology, Ankara, Turkey; 3 Hacettepe University Faculty of Medicine, Department of Pediatric Pathology, Ankara, Turkey; 4 Hacettepe University Faculty of Medicine, Department of Pediatrics, Neonatology, Ankara, Turkey Magnetic resonance imaging (MRI) findings of merosin-deficient congenital muscular dystrophy include diffuse white matter changes involving both hemispheres and sparing corpus callosum, brainstem, internal capsule and cerebellum. Reports in literature generally shows white matter changes beginning from 6 months of age, however we suggest that they may be present at the neonatal period especially on T2-weighted (W) fast spin-echo imaging (FSEI) through illustration of this 5 days-old neonate. The patient is a full-term male infant born with a birth weight of 3800 g, with APGAR scores of 9 at 1 min and 10 at 5 min, who was transferred to neonatal intensive care unit because of respiratory difficulty. There was first degree consanguinity and the family refused prenatal diagnosis despite a previous 3-year-old boy with a diagnosis of merosin-deficient congenital muscular dystrophy. Physical examination on the first day of life showed mild contractures of the knees. Serum CK level was 1071 IU/L (N < 200). MRI was performed on 5th day of life. A vastus lateralis biopsy showed totally merosin-deficient fibers. Current routine MRI protocol in our institute was employed on a 1.5 T MR system. T2W FSEI clearly showed polymicrogyria prominent on bilateral frontal and temporooccipital regions, with cell sparse zone in the occipital lobes. There were periventricular white matter abnormalities and acute punctate ischemic lesions in the right frontal and left parietal regions. Extensive white matter changes simulating a leukodystrophy is a classical finding in merosin-deficient congenital muscular dystrophy. T2W FSEI is especially of value in demonstration of both gray and white matter abnormalities in the neonate in which the brain parenchyma contains greatest amount of water and least myelin. However to better understand the early white matter changes and evolution of the central nervous system involvement, serial MRI studies can be performed beginning from the neonatal period. doi:10.1016/j.nmd.2006.05.074

P.P.1 06 Magnetic resonance imaging and spectroscopy findings in a patient with partial merosin deficiency G. Haliloglu 1, K. Karli Oguz 2, A. Ozturk 2, Z. Akcoren 3, M. Caglar 3, H. Topaloglu 1,* 1 Hacettepe University Faculty of Medicine, Department of Pediatric Neurology, Ankara, Turkey; 2 Hacettepe University Faculty of Medicine, Department of Radiology, Ankara, Turkey; 3 Hacettepe University Faculty of Medicine, Department of Pediatric Pathology, Ankara, Turkey