Variable histological expression of dystrophinopathy in two females

Abstract

We report two carriers of Xp21 muscular dystrophy with unusual clinical manifestations and striking variability of dystrophin deficiency within the same muscle biopsy. The first patient was a 60-year-old nun with recent onset of cramps and proximal weakness, mimicking an acquired myopathy. Muscle biopsy disclosed slight alterations in one sample and severe dystrophic changes in another; dystrophin was absent in 7% fibers in the former specimen and in 60% in the second. X inactivation was skewed with 90% cells inactivating the same X chromosome. The second patient was a 17-year-old girl with hyperCKemia, learning disability and a family history of X-linked muscular dystrophy. Muscle biopsy displayed slight fiber size variability and some internal nuclei; dystrophin was absent only in one muscle fiber. A second sample with the same morphological features demonstrated dystrophin deficiency with mosaic distribution. The pattern of X inactivation was normal. These cases emphasize the variability of histopathological changes and dystrophin deficiency in Xp21 muscular dystrophy carriers and the risk of sampling errors in muscle biopsy.

Unusual Clinical Expression of Dystrophinopathy in a Female, Mimicking a Congenital Myopathy

“…In the presented case the severe dystrophin deficiency could also result from sampling and it might reflect the fallacy of assuming that the muscle biopsy is representative of the entire musculature: recently we observed a Xp21 manifesting carrier with dramatic variability of morphological changes, paralleling dystrophin expression, in two different samples of the same biopsy [26]. Skewed X-inactivation has been related to the severity of clinical expression of dystrophinopathy in females [17]: however, unlike the severely affected males, the course of dystrophinopathy in females is less easily predictable and it might depend on the balance between the tendency for the muscle either to normalize or to degenerate as a response to loss of dystrophin in negative fibers [17].…”

Histopathological features in subsequent muscle biopsies in a warmblood mare with myotonic dystrophy

“…The changing or variable histopathological picture seen in the current case has not been described in equine myopathies yet, but it is known in some human neuromuscular diseases especially congenital myopathies (Donner et al 1975;Doriguzzi et al 1999;Jungbluth et al 2008;Romero et al 2010). There are two reports about atypical histopathological findings in congenital or infantile myotonic dystrophy presenting several cases of genetically confirmed myotonic dystrophy as myositis or congenital fibre type disproportion (Lukas et al 2007;Tominaga et al 2010).…”