Variable histological expression of dystrophinopathy in two females

We report two carriers of Xp21 muscular dystrophy with unusual clinical man ifestations and striking variability of dystrophin deficiency within the sa me muscle biopsy. The first patient was a 60-year-old nun with recent onset of cramps and proximal weakness, mimicking an acquired myopathy. Muscle bi opsy disclosed slight alterations in one sample and severe dystrophic chang es in another; dystrophin was absent in 7% fibers in the former specimen an d in 60% in the second. X inactivation was skewed with 90% cells inactivati ng the same X chromosome. The second patient was a 17-year-old girl with hy perCKemia, learning disability and a family history of X-linked muscular dy strophy. Muscle biopsy displayed slight fiber size variability and some int ernal nuclei; dystrophin was absent only in one muscle fiber. A second samp le with the same morphological features demonstrated dystrophin deficiency with mosaic distribution. The pattern of X inactivation was normal. These c ases emphasize the variability of histopathological changes and dystrophin deficiency in Xp21 muscular dystrophy carriers and the risk of sampling err ors in muscle biopsy.