Neonatal fractures as a presenting feature of LMOD3-associated congenital myopathy.

TitleNeonatal fractures as a presenting feature of LMOD3-associated congenital myopathy.
Publication TypeJournal Article
Year of Publication2017
AuthorsAbbott, M, Jain, M, Pferdehirt, R, Chen, Y, Tran, A, Duz, MB, Seven, M, Gibbs, RA, Muzny, D, Lee, B, Marom, R, Burrage, LC
JournalAm J Med Genet A
Volume173
Issue10
Pagination2789-2794
Date Published2017 Oct
ISSN1552-4833
Abstract

Nemaline myopathy is a rare inherited disorder characterized by weakness, hypotonia, and depressed deep tendon reflexes. It is clinically and genetically heterogeneous, with the most severe phenotype presenting as perinatal akinesia, severe muscle weakness, feeding difficulties and respiratory failure, leading to early mortality. Pathogenic variants in 12 genes, encoding components of the sarcomere or factors related to myogenesis, have been reported in patients affected with the disorder. Here, we describe an early, lethal presentation of decreased fetal movements, hypotonia, muscle weakness, and neonatal respiratory failure requiring ventilator support in three siblings from a consanguineous family. All exhibited perinatal fractures, and thus, a skeletal dysplasia was considered as possibly contributing to the phenotype. However, whole exome sequencing revealed a homozygous, loss-of-function pathogenic variant in LMOD3, which has recently been associated with nemaline myopathy and, in a subset of patients, perinatal fractures. This case demonstrates the importance of considering congenital neuromuscular disorders in the differential diagnosis of perinatal fractures.

DOI10.1002/ajmg.a.38383
Alternate JournalAm. J. Med. Genet. A
PubMed ID28815944
PubMed Central IDPMC5603416
Grant ListK08 DK106453 / DK / NIDDK NIH HHS / United States
U54 HG006542 / HG / NHGRI NIH HHS / United States
T32 GM007526 / GM / NIGMS NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P30 HD024064 / HD / NICHD NIH HHS / United States
P01 HD070394 / HD / NICHD NIH HHS / United States