Abstract Details

Title Thirty-three Years to Diagnosis: Distal Hereditary Motor Neuropathy Type VA with a Novel Variant in BSCL2

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)

Poster/Presentation
Number 079

Objective To report a case of distal hereditary motor neuropathy type VA (dHMN-VA) with a novel BSCL2 variant, misdiagnosed as spinal muscular atrophy (SMA).

Background Hereditary motor neuropathies (HMN) are uncommon. Early accurate genetic diagnosis to differentiate from SMA is critical, as the latter now has multiple available therapies. The widespread availability of genetic testing has allowed identification of genetic causes of previously undiagnosed or misdiagnosed neuromuscular disorders.

Design/Methods Case report.

Results A 67-year-old woman carrying a diagnosis of SMA was identified through a search of the electronic medical record. Old records were reviewed, and she had a detailed neuromuscular evaluation. She presented at age 33 with weakness of finger extension. She reported longstanding hand cramps and spasms, worsened by cold weather. She underwent extensive testing over 10 years, which included normal brain and cervical magnetic resonance imaging, 4 electrodiagnostic studies which demonstrated a chronic neurogenic process, normal creatine kinase and multiple tests for metabolic, toxic, infectious and autoimmune causes of neuropathy. A biceps muscle biopsy showed chronic denervation changes, which were thought to be consistent with SMA. Genetic testing was not available at the time. Our evaluation was 33 years after the initial presentation. Exam demonstrated asymmetric atrophy and weakness of hand and forearm muscles, predominantly of finger extensors. Brachioradialis and ankle reflexes were diminished. The rest of the exam was unremarkable. Genetic testing for 5q-related SMA was normal, with 2 copies of SMN1. Further testing for hereditary motor neuropathies demonstrated a heterozygous c.274 A>G p.T92A variant in BSCL2, which was interpreted as a variant of uncertain significance.

Conclusions The pattern of weakness in distal HMN differs from 5q-SMA, which is predominantly proximal. Cramps worsened by cold temperature are a distinctive feature of dHMN-VA. We propose the patient’s phenotype and electrophysiologic findings support a pathogenic effect for this variant in BSCL2.

Authors/Disclosures
John Herbst, DO (Allegheny Health Network Cancer Institute) PRESENTER	Dr. Herbst has nothing to disclose.
J. David Avila, MD, F�鶹��ýӳ�� (Geisinger Medical Center)	Dr. Avila has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AstraZeneca. Dr. Avila has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Alnylam Pharmaceuticals. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for argenx. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for UCB. Dr. Avila has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for AstraZeneca. Dr. Avila has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda.
	No disclosure on file

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