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#apaperaday: A manifesting female carrier of Duchenne muscular dystrophy: Importance of genetics for the dystrophinopathies

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: A manifesting female carrier of Duchenne muscular dystrophy: Importance of genetics for the dystrophinopathies

Today’s pick is an educational paper on a female with dystrophinopathy by Quak et al in the Singapore Medical Journal. The paper starts out as a case report but then also provides context on dystrophinopathies in general. DOI: 10.4103/singaporemedj.SMJ-2021-356

Authors introduce how Duchenne and Becker are caused by pathogenic variants in the dystrophin gene, which is on the X-chromosome. Most females with variants on 1 X-chromosome have no symptoms, but some do, such as the 55 year old Chinese women described here.

The woman had a history of lower limb weakness since adolescence, currently walked with a stick and had a son with Duchenne (diagnosed on absence of dystrophin on biopsy). CK was slightly elevate (~600 U/L). She also had respiratory failure and cardiomyopathy

Note authors performed lung & heart function analyses when they realized the woman had female dystrophinopathy. The mutation was not identified (genetic analysis was declined). Authors argue while this means dystrophinopathy is not confirmed for the women it is very likely. The symptoms fit and the fact that her son has Duchenne means she has a 2/3 chance of being a carrier of the mutation. The woman was then offered multidisciplinary care, received cardiac medication and is on nocturnal ventilation.

3 years after presenting in the clinic she lost ambulation. Her heart is currently doing better but authors indicate this may be due to reduced strain after losing ambulation. In the discussion authors provide context on dystrophin, genetic diagnosis and counseling… They stress that 2/3 women with a son with Duchenne will be carriers, but that the 1/3 women who are not carriers are still at risk of having more children with Duchenne (boys) or carriers (girls) because part of the germ cells (eggs) carry the pathogenic variant.

Authors also explain the difference between Duchenne and Becker (no dystrophin vs partially functional dystrophin) and outline that cognitive problems can co-occur in dystrophinopathy patients (the woman had no cognitive problems). Authors outline that while most females with dystrophinopathy have milder symptoms than Duchenne, women CAN have Duchenne, e.g. when they have a translocation, only 1 X chromosome (Turner) or 2 X chromosomes from 1 parent, or 2 affected X chromosomes (one from each parent)

This was also outlined by Alessandra Ferlini during World Duchenne Awareness Day 2022 – the theme was women and Duchenne. Authors outline how to diagnose dystrophinopathies stressing that biopsies are generally no longer needed.

Finally they outline the importance of multidisciplinary care and currently approved drugs in Europe and the USA. A very comprehensive way to provide the most important context for dystrophinopathies with a focus on females but also males. Well done and indeed educational.