Raveen R. Sugantharaj, DO
Resident Physician 4
UNC PMR
Durham, North Carolina, United States
Elyse N. Swope, DO, DO
PGY-2 Resident Physician, PM&R
UNC School of Medicine
Efland, North Carolina, United States
59-year-old female with 1 year of progressive dysphonia and distal weakness
Case Description:
If a potentially debilitating condition existed in your genetics, would you want to know? Our patient presented for electrodiagnostic evaluation (EDx) after recognizing symptoms of her late brother and father - both passed from complications of a muscular disorder. These symptoms: handgrip weakness, ankle instability with frequent falls, and dysphonia, developed over 12 months. EMG revealed spontaneous activity, early recruitment, and p<span style="font-size: 11.0pt; line-height: 107%; font-family: 'Arial',sans-serif; mso-fareast-font-family: 'Times New Roman'; mso-font-kerning: 0pt; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">olyphasicity predominantly in tibialis anterior, consistent with irritable myopathy. A patient-guided search identified the article, American Journal of Human Genetics 63,1732:42,1998, outlining the symptomology and genetics of her familial condition. The irritable myopathy resembles a multisystem proteinopathy secondary to autosomal dominant VCP mutation. Referral to Neuromuscular clinic was made for advanced genetic testing and symptom monitoring/management.
Discussions: Weakness of hands/feet is pathognomonic for distal myopathies, however, VCPDM is distinguishable by pharyngeal weakness (VCPD) without oculomotor involvement. The article identified 37 relatives, all with variations of vocal cord, finger and ankle extensor weakness with similar electrodiagnostic findings. Genetic mapping localized the VCPDM mutation to chromosome 5q- present in 3 familial genomes globally. In 1998, the protein coded by VCP and its role were unknown; we now know it plays a significant role in cellular maintenance and muscle protein degradation. During cellular repair, VCP degrades misfolded proteins. When mutated, accumulation of faulty proteins causes muscle tissue dysfunction. Conditions like tibial muscular dystrophy, oculopharyngodistal or inclusion body myopathies have overlapping symptoms to VCPD. Consequently, a thorough history, electrodiagnostics, muscle/nerve biopsies, and genetic testing are critical for accurate diagnoses.
Conclusions: Genetic myopathies should be considered in middle-aged adults with progressive, distal extremity weakness. VCP myopathy features inclusion of pharyngeal weakness without oculomotor involvement. While management is supportive, late complications such as dysphagia/aspiration and respiratory/cardiac compromise justify the importance of prompt diagnosis and medical surveillance.
