263rd ENMC International Workshop: Focus on female carriers of dystrophinopathy

#apaperaday 

Prof. Annemieke Aartsma-Rus is taking on a challenge by reading and commenting on a paper a day. She shares her insights, findings and thoughts via her @oligogirl Twitter account. See below the overview of February 2023.

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Prof. Aartsma-Rus reads and comments on the paper titled: 263rd ENMC International Workshop: Focus on female carriers of dystrophinopathy: refining recommendations for prevention, diagnosis, surveillance, and treatment.

#apaperaday Today’s pick is not yet on Pubmed but a corrected proof is available World Muscle Society journal Neuromuscular Disorder. It is the report of the 263rd ENMC workshop on female carriers of dystrophinopathy DOI:https://doi.org/10.1016/j.nmd.

As always with ENMC workshop reports there is a lot of content. I will focus only on the highlights – you can read the entire report if you want details. The meeting took place in May 2022 and some excerpts were already shared by Alessandra Ferlini during World Duchenne Awareness Day 2022.

ENMC workshops for those not familiar with the concept: a small group (~20 participants) of different geographic background, expertise and stakeholdership (patient reps, basic scientists, clinicians etc) meet from Friday-Sunday to discuss a specific topic in depth.

A lot of preparation happens ahead of the meeting to cover the crucial aspects for the chosen topic. For this workshop 2 online preparation sessions and several questionnaires were sent out. The topic was female carriers of pathogenic variants in the DMD gene (DMD carriers).

Elizabeth Vroom presented a questionnaire done with DMD carriers, which highlighted unmet needs such as psychological support, the desire to have genetic testing done earlier and/or reimbursed and increasing awareness with clinicians that this group can also have symptoms.

The group agreed on a new term for carriers with symptoms: females with dystrophinopathy. Symptoms can be elevated creatine kinase levels (marker for muscle damage), muscle weakness, muscle pain and also cardiomyopathy.

There was discussion about skewed X-inactivation and its relationship to resulting in dystrophinopathy in females – for now this topic needs more study (see also my threads during #WDAD2022 about this topic).

Participants agreed that currently there is no consensus for how to best manage females with dystrophinopathy. They suggest the following:

1. Genetic testing of females at risk of being a carrier at age 16 or earlier when there are symptoms (muscle or cognitive!)
2. For DMD carriers follow up should be done by a neuromuscular specialist and cardiologist shortly after the genetic diagnosis and then every 3-5 years or more frequently if symptoms arise. Having no symptoms at a specific age, does not mean they will not develop later.
3. Awareness needs to be increased with carriers that they are at risk of having muscle problems, cardiomyopathy and learning difficulties. Similarly awareness needs to be increased with clinicians.
4. Specific registries for DMD carriers are needed as well as natural history studies. Currently females with dystrophinopathy are excluded from participating in clinical trials because of all the unknowns. Collecting data will help design trials for them.

As mentioned, these are just the highlights. There is much more in the report. I would like to thank the organizers for making the world aware that this topic is hardly researched and that these women deserve research and care.

About Professor Annemieke Aartsma-Rus

Prof. Dr. Annemieke Aartsma-Rus is a professor of Translational Genetics at the Department of Human Genetics of the Leiden University Medical Center. Since 2013 she has a visiting professorship at the Institute of Genetic Medicine of Newcastle University (UK).

Her work currently focuses on developing antisense-mediated exon skipping as a therapy for Duchenne muscular dystrophy. In addition, in collaborative efforts she aims to bridge the gap between different stakeholders (patients, academics, regulators and industry) involved in drug development for rare diseases.

In 2013 she was elected a member of the junior section of the Dutch Royal Academy of Sciences (KNAW), which consists of what are considered the top 50 scientists in the Netherlands under 45. From 2015 to 2022, she was selected as the most influential scientist in Duchenne muscular dystrophy by Expertscape.