Abstract Details

Title Two Cases of Spinal Muscular Atrophy due to Mutations in the VRK1 Gene

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-005

Objective To expand knowledge of the range of clinical phenotypes associated with mutations in the VRK1 gene.

Background The vaccinia related kinase 1 (VRK1) gene is a gene located on chromosome 14q32 that was fairly recently identified as associated with SMA, particularly a phenotype of SMA with pontocerebellar hypoplasia (SMA-PCH). Currently known clinical syndromes include infantile onset disease with microcephaly, intellectual disability, and sensorimotor neuropathy as well as adult onset weakness with features consistent with amyotrophic lateral sclerosis.

Design/Methods We present case reports of 2 patients with slowly progressive weakness and clinical syndrome consistent with adult onset spinal muscular atrophy. Neither had pontocerebellar hypoplasia.

Results Genetic testing revealed likely pathogenic variants in the VRK1 gene in both patients. One patient had homozygous p.R321C (c.961 C>T), likely pathogenic variant. The other had compound heterozygous p.V236M (c.706 G>A) and p.R321C (c.961 C>T), likely pathogenic variants. Notably, both patients were of Hispanic descent and these two variants are reported to be more prevalent in the Latino population.

Conclusions

We report 2 cases with VRK1 mutations presenting as adult onset spinal muscular atrophy without pontocerebellar hypoplasia. Genetic testing in patients like ours is important in order to expand understanding of the clinical spectrum of this disorder. Moreover, the spectrum and carrier frequency of pathogenic variants in VRK1 appears to be different in individuals of Ashkenazi and Hispanic descent.

Authors/Disclosures
Angela R. Sung, MD (Sharp Rees-Stealy Medical Group) PRESENTER	No disclosure on file
Paolo M. Moretti, MD (University of Utah)	The institution of Dr. Moretti has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie, Inc. The institution of an immediate family member of Dr. Moretti has received research support from NIH. The institution of an immediate family member of Dr. Moretti has received research support from VHA. The institution of an immediate family member of Dr. Moretti has received research support from DOD.
Aziz I. Shaibani, MD, FAAN (Houston Neurocare, PA)	Dr. Shaibani has nothing to disclose.

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