Severe Neonatal RYR1 Myopathy With Pathological Features of Congenital Muscular Dystrophy. J Neuropathol Exp Neurol 2019 Mar 01;78(3):283-287
Date
02/05/2019Pubmed ID
30715496Pubmed Central ID
PMC6380315DOI
10.1093/jnen/nlz004Scopus ID
2-s2.0-85063882669 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
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.
Author List
Helbling DC, Mendoza D, McCarrier J, Vanden Avond MA, Harmelink MM, Barkhaus PE, Basel D, Lawlor MWAuthors
Paul E. Barkhaus MD Professor in the Neurology department at Medical College of WisconsinDonald Basel MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Matthew Harmelink MD Chief, Associate Professor in the Neurology department at Medical College of Wisconsin
Michael W. Lawlor MD, PhD Adjunct Professor in the Pathology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Fatal OutcomeHumans
Infant, Newborn
Male
Muscular Diseases
Muscular Dystrophies
Ryanodine Receptor Calcium Release Channel
Severity of Illness Index
