Diagnostik kongenitaler Muskeldystrophien

Zusammenfassung

Die kongenitalen Muskeldystrophien (CMD) sind eine heterogene Gruppe autosomal-rezessiv vererbter Erkrankungen. In den letzten Jahren ist es gelungen, bei einer Reihe von CMDs das mutierte Gen und das Genprodukt zu identifizieren. Dabei ist deutlich geworden, dass besonders für die schweren Verlaufsformen der CMD mit Beteiligung des ZNS Glykosylierungsstörungen patho-physiologisch relevant zu sein scheinen. Von zentraler Bedeutung für die Diagnostik ist die immunhistochemische Untersuchung des Muskels. Anhand der Unterscheidung in Laminin-α2-positive und -negative sowie α-Dystroglykan-positive und -negative CMD wird weitergehende immunhistologische und molekulargentische Diagnostik veranlasst. Ist der histologische Befund spezifisch, kann eine gezielte Mutationsanalyse erfolgen, bei einem unspezifischen Befund können bei einer aussagekräftigen Familienkonstellation Genorte durch Haplotypisierung ausgeschlossen bzw eingegrenzt werden. MRT, der ophthalmologische Befund und die neurophysiologische Untersuchungen können wichtige differenzialdiagnostische Hinweise liefern.

Summary

Congenital muscular dystrophies (CMD) are a heterogeneous group of autosomal recessively inherited diseases. In the last few years, in a number of CMDs the mutated genes and the gene products have been identified. It became clear that disturbance of glycosylation may be relevant in pathophysiology of CMD, particularly in severe forms with CNS involvement. Immunohistochemical staining of muscle is of decisive importance for further diagnostic planing. Based on the differentiation between laminin α2-positive and laminin α2-negative CMD as well as α-dystroglycan-positive and α-dystroglycan-negative CMD, further immunohistochemical and molecular genetic investigations will be performed. If the immunohistochemical staining reveals in a specific protein deficiency, such as decrease of collagen VI, a mutation analysis should be added. In the case of unspecific findings chromosomal regions may be excluded or more precisely defined by haplotyping. Magnetic resonance imaging (MRI), ophthalmological findings and neurophysiological examinations may contribute important diagnostic hints.

Schlüsselwörter

Kongenitale Muskeldystrophie - α-Dystroglykan - Laminin α2 - Kollagen VI - Glykosylierung

Keywords

Congenital muscular dystrophy - α-dystroglykan - laminin α2 - collagen VI - glycosylation

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