Severe Neonatal RYR1 Myopathy With Pathological Features of Congenital Muscular Dystrophy.

Abstract

The phenotypes associated with pathogenic variants in the ryanodine receptor 1 gene (RYR1, OMIM# 180901) have greatly expanded over the last few decades as genetic testing for RYR1 variants has become more common. Initially described in association with malignant hyperthermia, pathogenic variants in RYR1 are typically associated with core pathology in muscle biopsies (central core disease or multiminicore disease) and symptomatic myopathies with symptoms ranging from mild weakness to perinatal lethality. We describe a 2-week-old male patient with multiple congenital dysmorphisms, severe perinatal weakness, and subsequent demise, whose histopathology on autopsy was consistent with congenital muscular dystrophy. Immunohistochemical analysis of dystrophy-associated proteins was normal. Rapid exome sequencing revealed a novel heterozygous nonsense variant (p.Trp661Ter) in RYR1, as well as a previously described RYR1 pathogenic variant associated with congenital myopathy (p.Phe4976Leu). This highlights the potential for RYR1 pathogenic variants to produce pathological findings most consistent with congenital muscular dystrophy.

• Authors: Daniel C Helbling, David Mendoza, Julie McCarrier, Mark A Vanden Avond, Matthew M Harmelink, Paul E Barkhaus, Donald Basel, Michael W Lawlor
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 78 Issue 3 Pg. 283-287 (03 01 2019) ISSN: 1554-6578 [Electronic] England
• PMID: 30715496 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2019 American Association of Neuropathologists, Inc. All rights reserved.

Chemical References

• RYR1 protein, human
• Ryanodine Receptor Calcium Release Channel

Topics

• Fatal Outcome
• Humans
• Infant, Newborn
• Male
• Muscular Diseases (genetics, pathology)
• Muscular Dystrophies (genetics, pathology)
• Ryanodine Receptor Calcium Release Channel (genetics)
• Severity of Illness Index