Ishizaki M, Kobayashi M, Adachi K, Matsumura T, Kimura E. Female dystrophinopathy: Review of current literature. Neuromuscular disorders : NMD 2018;28:572-581
Even though DMD and BMD are predominantly male diseases, some female carriers also present with disease symptoms. This article combines data available from several other articles. In nearly all cases this is due to skewed X-inactivation (the X-chromosome containing the functional DMD gene is more often inactivated than the chromosome containing the mutated (non-functional) DMD gene, leading to a decreased expression of the dystrophin protein). Among these carriers around 15% is non-ambulatory and around 17% presents with heart problems. Also among female carriers without disease symptoms heart abnormalities are found.
Skeletal muscle or cardiac symptoms are known to appear in a certain proportion of female patients carrying the dystrophin gene mutation. There is limited high-quality evidence to guide the treatment of female carriers of Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD). The available evidence is mainly based on expert opinions and clinical experience. To improve this situation, we reviewed 1002 reports published from 1967 to 2017 to assess the following themes: epidemiology, clinical symptoms, cardiomyopathy, burdens on parents or caregivers, pregnancy or delivery, and prognosis. We aimed to provide guidance for the provision of support, care, and education for patients, caregivers, and health care professionals. There were 271 reports before 1987, and 731 reports after 1987 when dystrophin was first recognized. In this review, we mainly selected 37 papers that were reported after 1987. In seven large research papers, the incidence of skeletal muscle damage among female carriers, including asymptomatic carriers, was reported as 2.5%-19%, and the incidence of dilated cardiomyopathy was 7.3%-16.7% for DMD and 0%-13.3% for BMD. We integrated and summarized the genetically definite manifesting carriers with skeletal muscle symptoms from 10 case series. In combined data, among 93 manifesting carriers, 16 (17.2%) presented with cardiac abnormalities. The frequency of manifesting carriers complicated by cardiomyopathy increased with age. Reports on cardiac magnetic resonance in female carriers and the burden on caregivers are increasing, whereas literatures concerning pregnancy, delivery, and prognosis in female carriers are limited. This represents a future direction for research.