#apaperaday: Newborn screening for Duchenne muscular dystrophy-early detection and diagnostic algorithm for female carriers of Duchenne muscular dystrophy

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled: Newborn screening for Duchenne muscular dystrophy-early detection and diagnostic algorithm for female carriers of Duchenne muscular dystrophy

Today’s pick is from the American Journal of Medical Genetics by Gruber et al on learnings from a newborn screening (NBS) pilot with regards to female carriers of dystrophin mutations doi 10.1002/ajmg.c.32000 collaboration with PPMD.

The dystrophin gene is located on the X-chromosome. This means that males with mutations in their one copy will get a disease (Duchenne: no dystrophin, severe progression; Becker: partially functional dystrophin, milder progression).

Females have a backup copy so generally women with mutations on one copy do not have symptoms. But, as was the focus of World Duchenne Awareness Day 2022, females with mutations CAN have symptoms as well (females with dystrophinopathy).

Note that all female carriers are at risk for developing cardiomyopathy. NBS is not routinely done for dystrophinopathy (male and female). However pilots are done as earlier diagnosis allows family planning, reduce the diagnostic odyssey and earlier symptomatic interventions.

Authors discuss an NBS pilot study in New York State which was done in collaboration with PPMD and screened >36,000 newborns (male and female). Screening was 2 tiered: first CK in blood was measured. Molecular gene analysis was done for individuals with Elevated CK.

25 males and 17 females were studied with molecular gene analysis. One carrier of Duchenne mutation was identified. One individual was not further tested but the mother identified herself as a carrier (so likely the daughter is as well – 57% of carriers had elevated CK).

One carrier of a Becker mutation was identified too. When a high CK female baby was identified families were offered a consult with a counselor who explained the possibilities (female carrier, daughter with other muscle disease, some of which are treatable like Pompe).

When a carrier baby was identified this allowed follow up to assess development of cardiomyopathy and also prevented a long diagnostic odyssey in case the female developed symptoms (leading to liver biopsies on occasion).

It also allowed future analysis in the family: brothers could have Duchenne or Becker without symptoms, sisters, mothers, aunts etc can be a carrier. This has implications for family planning but also these women are at risk for cardiomyopathy and developing muscle symptoms.

Authors stress many carrier females have emotional distress. Often these females have a son with Duchenne. Research is also needed to study carriers in general, with and without symptoms to allow offering them proper and adequate support.

So as is often the case more research is needed. Looking forward to this and kudos to the authors for this thoughtful review and perspective.