1/262. A novel form of familial congenital muscular dystrophy in two adolescents.We report on two brothers (the product of first-degree consanguineous marriage; aged 15 and 12 years) who presented with severe hypotonia at birth, proximal muscle weakness associated with delayed motor milestones but normal cognitive function. Investigations (at 4 years of age) revealed mildly elevated serum creatine kinase (CK) levels (300 and 824 IU/l; N < or = 210). Muscle biopsies showed minimal change myopathy, no neurogenic atrophy but remarkable type-1 fibre predominance (up to 85.5%) without fibre-type disproportion. Clinical examination at 12 and 9 years, respectively, showed mild facial weakness and high-arched palate in both patients. The younger sibling also had ptosis but otherwise normal external ocular muscles. They showed symmetric proximal muscle weakness and wasting associated with calf-muscle hypertrophy. They could walk independently. A repeat muscle biopsy showed advanced dystrophic changes in the younger patient at the age of 10 years. Virtually all the remaining fibres were type 1. immunohistochemistry revealed normal expression of the dystrophin-glycoprotein complex (DGC), including dystrophin, beta-dystroglycan, alpha-(adhalin), beta-, gamma-, and delta-sarcoglycan, laminin-alpha2 chain (merosin) and syntrophin. Mild dystrophic features and type-1 fibre predominance (92.5%) were seen in the biopsy of the older patient, whereas immunohistochemistry showed normal expression of the DGC. Both cases also showed clear expression of integrin alpha7 at the muscle fibre surface and in the blood vessels. Three years later, they could still walk, but with difficulty, and the older brother showed enlargement of the tongue and echocardiographic features of left ventricular dilated cardiomyopathy.- - - - - - - - - - ranking = 1keywords = congenita (Clic here for more details about this article) |
2/262. Merosin-deficient congenital muscular dystrophy associated with abnormal cerebral cortical gyration: an autopsy study.We report clinical, biopsy and autopsy findings in a merosin-deficient congenital muscular dystrophy (CMD) infant with abnormal cortical gyration. Brain showed polymicrogyria and occipital agyria with marginal neuroglial heterotopia and inferior vermis hypoplasia. There was a normal pattern of myelination consistent with early age. laminin alpha 2 chain was also absent in myocardium, brain pial-glial membrane, brain and skin blood vessels as well as intramuscular and skin nerves. Occasional basal lamina gaps were found in muscle fibres but not in brain-blood vessels. This is the first autopsy study in a merosin-deficient CMD case with abnormal cortical gyration.- - - - - - - - - - ranking = 1.25keywords = congenita (Clic here for more details about this article) |
3/262. Merosin-positive congenital muscular dystrophy with transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.The congenital muscular dystrophies (CMDs) are a heterogeneous group of disorders. Among these, the laminin alpha 2 chain 'merosin' deficient CMD is caused by mutations of the LAMA2 gene on chr 6q2 and Fukuyama CMD is linked to chr 9q31. We report a 7-year-old boy who was born to consanguineous healthy parents. His motor and mental development were slow. creatine kinase (CK) was elevated (2.100 U/l), and the muscle biopsy was dystrophic. He sat unsupported at 12 months and took his first steps at 3 years of age. At 6 years of age he could walk up to 500 m. He was mentally retarded and spoke single words only. At 1 year, MR imaging of the brain showed abnormal increased periventricular T2-signal, consistent with dysmyelination as well as pontocerebellar hypoplasia and several cerebellar cysts. The pattern of gyration was normal. Follow-up at 4 years showed normalization of the previously abnormal periventricular T2-signal. Immunohistochemical analysis of the skeletal muscle showed normal expression of laminin alpha 2 for a C-terminal antibody and antibodies to the 300 and 150 kDa fragments, as well as of laminins alpha 5, beta 1, beta 2 and gamma 1. The boy has two healthy younger brothers. Linkage analysis excluded the candidate loci on chromosomes 6q2 and 9q31. As such, the patient's data are suggestive of a new form of laminin alpha 2 positive CMD characterized by transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.- - - - - - - - - - ranking = 1.25keywords = congenita (Clic here for more details about this article) |
4/262. Merosin-positive congenital muscular dystrophy in two siblings with cataract and slight mental retardation.We report on two siblings that have been followed for 14 years, with merosin-positive congenital muscular dystrophy (CMD), cataract, retinitis pigmentosa, dysversion of the optic disc, but no cerebral anomalies, except for microcephaly and slight mental retardation (MR). The younger child had three generalized seizures easily controlled by anticonvulsant therapy. Both children presented hypotonia from birth, delayed psychomotor development, generalized muscular weakness, and atrophy and joint contractures of knees and ankles. The course of the disease, apparently static during the first 10 years of life, became progressive during the second decade with loss of deambulation by the age of 13. creatine kinase was increased in both children. Bilateral cataract was diagnosed at 6-months of age. In spite of the occurrence of microcephaly, MR was slight and the siblings acquired reading and writing skills after the aged 10. head magnetic resonance imaging showed normal results in both siblings. The classification of these cases within the broad spectrum of CMD is difficult since most of the known muscle-eye-brain syndromes generally show severe MR and brain anomalies. We consider these cases as corresponding to the rarer syndromes of merosin-positive CMD with associated features such as cataract and MR that were particularly emphasized during the 50th ENMC International Workshop on CMD [Dubowitz V. Workshop report: 50th ENMC International workshop on congenital muscular dystrophy. Neuromusc Disord 1997;7:539-547]. Further genetic, pathological, neuroradiological, and immunocytochemical studies will be necessary for better elucidation of the classification and pathogenesis of CMD.- - - - - - - - - - ranking = 1.5keywords = congenita (Clic here for more details about this article) |
5/262. Congenital muscular dystrophy with central and peripheral nervous system involvement in a Belgian patient.We report a patient with congenital muscular dystrophy (CMD), developmental brain defects, and peripheral neuropathy. Marked hypotonia and plagiocephaly were noted at birth. failure to thrive, generalized muscle weakness and wasting, absent deep tendon reflexes, partial seizures, and secondary microcephaly developed. Brain MRI showed a large area of cortical dysplasia, a thin but complete corpus callosum, and diffuse ventriculomegaly. Nerve conduction velocities were slow and creatine kinase levels only mildly elevated. Muscle biopsy showed dystrophic features with normal merosin, sarcoglycan, and dystrophin immunostaining. The Japanese Fukuyama CMD founder mutation was not detected. This is the first report of a patient with merosin-positive CMD, cobblestone lissencephaly, and demyelinating peripheral neuropathy.- - - - - - - - - - ranking = 0.25keywords = congenita (Clic here for more details about this article) |
6/262. genetic heterogeneity of congenital muscular dystrophy with rigid spine syndrome.Rigid spine syndrome is a neuromuscular disorder characterised by early rigidity of the spine due to axial muscle contractures, generally associated with muscle weakness, limb-joint contractures, and often respiratory failure. This phenotype may be associated with several muscular diseases. In cases of merosin-positive congenital muscular dystrophies (CMD) with rigid spine syndrome, we have recently identified a new locus (RSMD1) on chromosome 1p35-36. In the present study, we report the clinical, morphological and genetic analysis of other patients affected by a CMD with rigid spine syndrome from nine consanguineous families. Homozygosity mapping showed that the disease was linked to RSMD1 in one of the nine families. The other families were excluded from RSMD1, and the patients presented highly variable phenotypes suggesting the involvement of more than one gene defect in rigid spine syndrome. Nevertheless, a subgroup of patients who never walked, and had very early rigidity of the spine and scoliosis, may be considered for further genetic analysis.- - - - - - - - - - ranking = 1.25keywords = congenita (Clic here for more details about this article) |
7/262. Unusual clinical expression of dystrophinopathy in a female, mimicking a congenital myopathy.A 25-year-old woman with negative family history and delayed motor development presented hypotrophy of the right lower limb and calf hypertrophy since age 7 and she complained of muscle weakness since 23. Neurological examination showed a thin elongated face, high-arched palate, high-pitched voice, proximal wasting and weakness, impairment of distal muscles in the lower limbs. CK was 3, 034 U/l, EMG showed a myopathic pattern. Muscle biopsy displayed dystrophic features with diffuse dystrophin deficiency; immunoblotting demonstrated quantitative reduction of the protein and normal molecular weight. Lyonization study showed skewed X-inactivation with the maternal X active. Seven years' follow-up did not show progression of the disease.- - - - - - - - - - ranking = 1keywords = congenita (Clic here for more details about this article) |
8/262. Broader clinical spectrum of Fukuyama-type congenital muscular dystrophy manifested by haplotype analysis.Fukuyama-type congenital muscular dystrophy, walker-warburg syndrome, and muscle-eye-brain disease are clinically similar autosomal-recessive diseases, characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. The classification of these disorders remains controversial. We analyzed five patients with congenital muscular dystrophy from four families who had severe eye and brain anomalies, such as retinal dysplasia and hydrocephalus, using polymorphic microsatellite markers flanking the Fukuyama-type congenital muscular dystrophy locus on chromosome 9q31. All patients were heterozygous for the Fukuyama muscular dystrophy founder haplotype with 3-kb insertion. In three cases, the other chromosome without the 3-kb insertion exhibited the same haplotype with a nonsense mutation on exon 3 of the Fukuyama gene. Thus, these three patients were compound heterozygotes for the condition. Severe eye anomalies such as retinal dysplasia or detachment and hydrocephalus could be included in the clinical spectrum of Fukuyama muscular dystrophy. The clinical spectrum of this disease is much broader than previously presumed.- - - - - - - - - - ranking = 2keywords = congenita (Clic here for more details about this article) |
9/262. Mutations in the laminin alpha2-chain gene in two children with early-onset muscular dystrophy.We investigated two children who presented with delayed motor milestones. The first was a girl who was referred at 20 months because of developmental delay. She walked at 28 months and currently, aged 5 years, is independently mobile but has difficulty rising from the floor or going upstairs. The second was also a girl who presented at 6 weeks of age with hypotonia. Her motor milestones were delayed and she walked at the age of 2 years and 8 months and is currently independently mobile at the age of 3 years. serum creatine kinase was elevated and a muscle biopsy showed dystrophic changes in both children. immunohistochemistry of the laminin alpha2 chain of merosin was very similar in both cases: using a C-terminal antibody that recognizes an 80 kDa fragment, there was a mild reduction in expression on most fibres, while the staining with another antibody that recognizes a 300 kDa fragment showed a very marked reduction. Mutational analysis of the laminin alpha2 chain gene in the first patient showed that one of the two alleles had a de novo single nucleotide deletion at position 5702, causing a frameshift. In the other allele, we identified two point mutations present in cis; one was a G-->C transition at position 5 while the second was a T-->C transition at position 6 of the conserved donor splicing consensus sequence of introns 37 and 63, respectively. Transcription analysis of the corresponding cDNA region did not show any alternative splicing occurring as a result of these splice site mutations. Therefore, these mutations probably affect the splicing efficiency. Interestingly, the second child carried in both alleles the same two splicing consensus sequence mutations found in cis in the first patient. Our data provide further evidence that mutations in the laminin alpha2 chain gene are responsible not only for the severe form of congenital muscular dystrophy with onset at birth, but also for milder phenotypes, with later onset, in which the synthesis of a partially functional protein, or of a normal protein but in reduced quantity, is possible. The finding that these two unrelated patients had the same unusual mutation in common might suggest that this is a relatively commonly allele responsible for partial merosin deficiency in the UK.- - - - - - - - - - ranking = 0.25keywords = congenita (Clic here for more details about this article) |
10/262. walker-warburg syndrome. Report of two cases.The purpose of this study is to describe two infants that were diagnosed with walker-warburg syndrome (WWS), a rare form of congenital muscular dystrophy (CMD). They were studied in their clinical, laboratory, and neuroradiologic features. The index case had a brain magnetic resonance imaging (MRI) and the second patient had a head computerized tomography (CT). In addition, a literature review was performed to describe the main forms of CMD. The index case fulfilled all criteria for WWS. A brain MRI performed at age 4 months served to corroborate the clinical diagnosis, showing severe hydrocephalus, type II lissencephaly, cerebellar vermian aplasia, and a hypoplastic brain stem. The authors were able to establish a retrospective diagnosis of WWS in the index case's older sister, based upon her clinical picture and head CT report.- - - - - - - - - - ranking = 0.25keywords = congenita (Clic here for more details about this article) |
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