Poster Number: T304


Nader Boutros, MD, UCLA, Payam Soltanzadeh, MD, UCLA

The dystrophinopathies, including Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD), are inherited in an X-linked manner, with BMD being characterized by later-onset and milder phenotype. BMD has a very wide clinical spectrum and is distinguished clinically from DMD by the age at loss of ambulation. Typically, treatment-naive patients with BMD lose ambulation after age 15, but many can still be ambulatory to their later decades of life and some present with cardiomyopathy. To our knowledge, the latest reported age of onset is 54 years. We present a case of a very late onset BMD at 76 years of age, and with a new DMD variant c.5922+1G>T (Splice Donor) – that has been reported only once before in a dystrophinopathy patient.

Case presentation:
An 86-year-old man reported gradual decline in gait since age 76 exacerbated following a 3-week hospitalization. This ultimately led to frequent falls and seeking a neuromuscular evaluation at the age of 86. Neurologic examination showed proximal upper and lower extremity weakness, and intact sensory testing and reflexes. MRI of bilateral thighs found evidence of severe atrophy and fatty replacement of anterior and posterior compartment musculature. EMG with evidence of a non-irritable myopathy. Genetic testing showed a likely pathogenic variant, DMD c.5922+1G>T (Splice Donor). This variant disrupts the splice donor site of intron 41, which results in an in-frame deletion of exon 41 upon a neuromuscular assessment, one of his grandchildren showed subtle signs of proximal weakness.

BMD should still be a consideration in the elderly men. Genetic testing and counseling of family members is very important since the daughters are obligate carriers of DMD. We are also reporting a new DMD variant that has been reported only once before. Different variants at the same splice donor site – c.5922+2T>C, c.5922+3G>C, c.5922+4A>T, c.5922+5G>C – have been reported in patients affected with BMD. Therefore, this new variant is most likely pathogenic and most consistent with a mild BMD phenotype.