ناهمگوني در شكل شديد ديستروفي عضلاني مادرزادي

TEROGENITY IN SEVERE FORM OF CONGENITAL MUSCULAR DYSTROPHY

It has recently been demonstrated that merosin-deficient congenital muscular dystrophy (CMD) patients have a more severe clinical phenotype compared with merosin-positive ones. We have undertaken a detailed clinical study of 6 patients (20% of all CMD patients followed) with severe CMD who have never been able to stand or walk unsupported and in whom we have determined merosin status in skeletal,rnuscle. Immunohistochemical staining demonstrated total absence of merosin in only one patient who was also found to have abnormal myelination on brain MRI. The patientʹs first biopsy at 4 weeks of age revealed only scattered degenerating and regenerating fibers without other changes of muscular dystrophy. Second muscle biopsy at 7 months revealed severe muscular dystrophy. Merosin was absent in both biopsies. All other 5 merosin-positive severe CMD cases had normal brain imaging. In 3 cases there was no family history of the disease, but the mother of the 4th female patient had a milder form of muscular dystrophy with hypotonia since birth, suggesting an autosomal dominant mode of inheritance. Although merosin was present in all 5 patients, there were occasional fibers in 3 of them with only partial staining. This was seen predominantly in the degenerating fibers probably representing secondary rather than primary merosin deficiency. This study implies heterogeneity within a phenotypically homogeneous group of patients with a severe form of CMD. The merosin-deficient CMD appears to be less common in the studied population than in France, Turkey or England. Perhaps the increased incidence in those countries suggests a distant founder mutation, which would explain the scarcity of merosin-deficient CMD in a more heterogeneous population like the studied one. Furthermore, absence of merosin in a neonate with hypotonia and weakness should lead to the diagnosis of merosin-deficient CMD, although the dystrophic process may not be evident on muscle biopsy yet.