#apaperaday: Evolution of neuropsychological and behavioral profile in a cohort of pediatric patients with Becker muscular dystrophy in a longitudinal study

In today’s #apaperaday, Prof. Aartsma-Rus reads and comments on the paper titled:  Evolution of neuropsychological and behavioral profile in a cohort of pediatric patients with Becker muscular dystrophy in a longitudinal study

Paper from @LUMC_Leiden again at long last. Today’s pick is from @WorldMuscleSoc journal Neuromuscular diseases by Cumbo et al on neuropsychological profiles in a Becker cohort with longitudinal (1 year) follow up. DOI: 10.1016/j.nmd.2024.01.006

dystrophin has functions in maintaining muscle integrity but also has (not fully understood) functions in brain development and maintenance. As such, lack of one or more dystrophin forms results in progressive muscle wasting and can lead to cognitive and behavioral issues.

Generally, the more dystrophins are lacking, the worse the brain involvement is, with Dp140 playing an important role in brain development (promotor in intron 44 but start site in exon 51). Becker patients make partially functional muscle dystrophins.

Depending on the location of the mutation, they make partially functional other isoforms OR they miss some of these isoforms. e.g., a deletion of exon 50-51 will mean partially functional full-length dystrophins and Dp260, normal Dp71 and Dp116, but no Dp140.

This is a level of detail that the authors do not introduce, but it is important to remember, because it is easy to think Becker patients have partially functional dystrophins while this is only a given for the full-length forms.

Back to the paper: Duchenne patients experience cognitive and behavioral problems, and difficulty with executive functioning, problem-solving, planning, and have a higher incidence of ADHD. In Becker, this seems to also be the case, although it is not studied well.

Here, authors follow a cohort of 22 Becker patients aged 5-18 and do baseline and 1-year follow-up measurements (in 17). Note that these are Becker patients on the more severe end of the muscle pathology spectrum, as some patients have first symptoms in adulthood.

Authors do mention whether the mutation is after exon 30 (Dp260 affected) or exon 44 (Dp140 may be affected), but they do not go into any detail in the outcomes. Note that numbers are very small. Authors found their cohort to have normal IQs (9), with 4 below and 4 above average.

They did observe impaired working memory that did not progress over 1 year. Also, executive functioning and switching of tasks were impaired. Adaptive functioning was normal. Muscle function was stable over the 1-year follow-up (NSAA).

Authors discuss that 2 of the mutations were beyond exon 63, which are expected to result in severe cognitive issues in Duchenne. Lacking the mutations, it is difficult to speculate, but it is possible that the Dp71 forms were partially functional.

The stability of cognitive problems, with improvement in processing speed that was observed in 1 follow-up, has also been reported in Duchenne. Patients learn to manage with coping mechanisms. Authors did not stratify patients with and without puberty.

Authors outline that the sample size is small and the follow-up is short. So more work is needed. I agree. It is not possible to generalize based on such a small cohort.However, multiple small cohorts make a large one and it is good that these authors and also the BIND Project are studying brain involvement in all dystrophinopathy patients (Duchenne, Becker, and female dystrophinopathy).