Needle muscle biopsy for carrier detection in Duchenne muscular dystrophy: Part. 1. Light microscopy — Histology, histochemistry and quantitation

Abstract

Needle muscle biopsies from 14 genetically proven carriers of Duchenne muscular dystrophy (DMD), 14 possible carriers with elevated serum creatine kinase activity (SCK) and 37 possible carriers with normal SCK were compared with similar samples from 10 healthy volunteer females with the aim of identifying subtle changes that might aid carrier detection. Qualitative differences were similar to those previously reported and included variation in fibre size, an increase in the number of internal nuclei and fragmentation of the myofibrillar network. By visual assessment, only 11% of the biopsies were classified as unequivocally abnormal but quantitation of fibre type proportions, fibre diameters and the number of internal nuclei showed that 71% of definite carriers, 86% of possible carriers with elevated SCK and 78% of possible carriers with normal SCK had at least one feature that was significantly different from controls. The commonest abnormalities were an increase in the proportion of type 1 fibres, an alteration in the mean diameter ratio of type 1:type 2 fibres, an increase in the fibre diameter variation coefficient and an increase in the number of internal nuclei. The changes in definite carriers were not related to elevated SCK and several with normal SCK showed morphological differences. It was concluded that quantitation of morphological features is essential for a full appraisal of biopsies from DMD carriers and that this approach is a useful aid to carrier detection.