Duchenne is caused by lack of dystrophin. The dystrophin gene lies on the X-chromosome. As such, primarily males are affected, because females have a back up X-chromosome with a functioning dystrophin gene, while males with a mutation do not.
It has become clear that
1. Female ‘carriers’ can also have symptoms, this is called female dystrophinopathy
2. Duchenne muscular dystrophy is not only a disease of the muscles, but also of the brain with DMD patients having learning difficulties, lower IQ and behavioral issues.
What is less well studied is whether female carriers (with or without symptoms) have cognitive problems.
Here authors studied a group of 15 carriers from Italy age 8-22. An IQ test revealed that carriers had a lower IQ than average. In fact, 47% of carriers had a very low IQ (<70), which occurs at 2% in the population. Only 1 carriers had a high IQ (126). When comparing carriers with & without muscle symptoms, it became apparent those with symptoms had a lower IQ, while those without had a normal IQ of ~100. Authors checked whether this difference was due to the one outlier of 126 (no muscle symptoms), but this was not the case. All carriers in the study were able to produce Dp71, a small dystrophin isoform where Duchenne patients unable to produce it have generally very low IQ.
Duchenne patients who are unable to produce the Dp140 isoform generally have more cognitive problems than those who can produce the Dp140 isoform. Also for carriers this was seen: the 3 carriers who could not produce Dp140 had a lower IQ than those who could produce it. Note that all Duchenne patients cannot produce full length dystrophin isoforms with function in muscle and brain.
Authors performed a literature review and report that the reports generally concur with their case series:
Carriers can have cognitive problems and have a lower IQ, and those unable to produce Dp140 have more cognitive problems and a lower IQ.
Authors discuss that a limitation is the small series they studied.
I agree but you have to start somewhere. I commend the authors for highlighting this important topic: female dystrophinopathy is overlooked and cognitive problems for dystrophinopathy are overlooked. The combination is exponentially overlooked. So this needs more study and recognition and both Duchenne patients and female dystrophinopathy patients with learning problems need guidance and help. @EU_BIND studies this, but the project is almost over. It is clear that more work is needed.
