Signs and symptoms of carriers of non- DMD X-linked neuromuscular diseases: A scoping review

It has been known for long that females carrying pathogenic variants in the DMD gene often report symptoms and/or exhibit signs of the disease. However, a notable knowledge gap exists concerning the signs and symptoms of female carriers of other X-linked neuromuscular diseases (XLNMDs). This scoping review aims to provide a comprehensive outline of existing literature regarding the signs and symptoms of carriers of non-DMD XLNMDs to raise awareness among both researchers and clinicians. Three electronic databases were used for the literature search (PubMed, Embase, Web of Science). Studies on the signs and symptoms of carriers of non-DMD XLNMDs were included. We included 44 articles for this review with a total of 354 carriers of non-DMD XLNMDs (mean age 43.9 years, std. deviation 17.4). Muscular signs and symptoms were reported for 125 carriers (X-linked myotubular myopathy (XLMTM): n = 96 (65%); Kennedy's disease (KD): n = 25 (32%); X-linked recessive Charcot-Marie-Tooth disease (CMTXR): n = 2 (15%); Uruguay faciocardiomusculoskeletal syndrome (FCMSU): n = 1 (33%); Barth syndrome (BS): n = 1 (100%)). In terms of ancillary investigations, abnormalities in histopathology and imaging were the most frequent with 44 carriers having abnormalities found by these testing (XLMTM: n = 36 (24%); Emery-Dreifuss muscular dystrophy 1 (EDMD1): n = 4 (5%); KD: n = 4 (5%) / XLMTM: n = 18 (12%); EDMD1: n = 1 (1%); KD: n = 5 (6%); X-linked myopathy with postural muscle atrophy (XMPMA): n = 19 (83%); BS: n = 1 (100%)). A difference between the number of EDMD1 carriers with cardiovascular signs and symptoms (n = 2 (1%)) and the number of carriers with abnormal electrocardiography tests (n = 20 (23%)) was also noted. Carriers of non-DMD XLNMDs exhibit a variety of signs and symptoms that could impact quality of life, making it vital for clinicians to be aware of these patients.