Abstracts

Rationale: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) represent a spectrum of diseases resulting from abnormal expression of the protein, dystrophin. Though primarily involved in maintaining muscle integrity, dystrophin is also expressed in the central nervous system (CNS) and is believed to play a role in alterations in neuronal metabolism. This may explain the CNS manifestations of dystrophinopathies, as these patients have been shown to have an increased risk for developmental delay and seizures. The prevalence of cardiac manifestations (arrhythmias, heart failure, cardiomyopathy) in female carriers of mutations of the DMD gene on chromosome X have been studied and have led to current screening recommendations. However, CNS correlations have not been as well-described in this population.

Methods: Three female dystrophinopathy carriers were identified in our current clinic population. Two of the three patients were found to have epilepsy and learning/developmental difficulties.


Results: Patient 1: 14-year-old with duplication of exon 6 and multiple areas of homozygosity. Her CK levels have been normal, but she does experience easy fatigability. She has developmental delay, abnormal MRI of the brain (mild cerebellar vermian hypoplasia) and generalized epilepsy. She was diagnosed with epilepsy at 8 years of age. Her EEG demonstrated generalized myoclonic-tonic seizures. Seizures are controlled with valproic acid and clobazam.

Patient 2: 16-year-old with deletion of exons 45-50. Her CK levels range from 2000-8500, and her clinical manifestations consist of pain and easy fatigability. She has learning difficulties and epilepsy, which she was diagnosed with at 6 years of age. Her most recent EEG demonstrated generalized 3-4 Hz spike-wave and polyspike-wave discharges. Her previous EEGs had bilateral frontal-central-parietal discharges. Seizures have been controlled on levetiracetam.

Conclusions: Female carriers of DMD and BMD may be at a higher risk for developmental delay and epilepsy compared to the general population. Larger studies are needed to better understand this association.


References:

Anand A, et al. Dystrophin induced cognitive impairment: mechanisms, models and therapeutic strategies. Ann Neurosci. 2015 Apr;22(2):108-18. doi: 10.5214/ans.0972.7531.221210. PMID: 26130916; PMCID: PMC4480258.

Armiho-Gomez JA, et al. Epilepsy in Duchenne and Becker Muscular Dystrophies. Annals of Clinical and Translational Neurology. 2024 May. doi:10.1002/acn3.52058.

Cho, Y. N., & Choi, Y.-C. (2013). Female Carriers of Duchenne Muscular Dystrophy. Journal of Genetic Medicine, 10(2), 94–98. https://doi.org/10.5734/jgm.2013.10.2.94

Pascual-Morena C, et al. Epileptic disorders in Becker and Duchenne muscular dystrophies: a systematic review and meta-analysis. J Neurol. 2022 Jul;269(7):3461-3469. doi: 10.1007/s00415-022-11040-y. Epub 2022 Mar 1. PMID: 35229191.

Ramani PK, Fawcett K, Guntrum D, Samuel H, Ciafaloni E, Veerapandiyan A. Epilepsy Characteristics in Duchenne and Becker Muscular Dystrophies. Child Neurol Open. 2023 Feb 22;10:2329048X231159484. doi: 10.1177/2329048X231159484. PMID: 36844469; PMCID: PMC9950600.


Funding: None