P.9.2 Autosomal dominant nemaline myopathy with marked intrafamilial phenotypic variability

We report a family of autosomal dominant (AD) myopathy with marked intrafamilial phenotypic variability.A 12month old female neonate presented with hypotonia, developmental delay and failure to thrive. The patient had lip cyanosis followed by cardiac arrest. After treatment, she was unable to wean the ventilator, and currently shows hypotonia, with slight improvement. The laboratory findings and brain imaging were unremarkable. Genetic tests for common inherited neuromuscular disorders returned normal. The muscle biopsy showed intranuclear rods with selective type 1 fiber atrophy. Electron microscopy demonstrated severe loss of myofibrillary structure with nemaline rod accumulation within atrophic fibers.The familial history revealed that the mother, grandfather, as well as younger sister and mother’s cousin experienced developmental delay. While patient‘s mother showed muscle atrophy in limb muscles on muscle computed tomography, none of them experienced any severe respiratory difficulties like the proband. On mutational analysis of ACTA1 and TPM3, a heterozygous missense mutation (c.32T>A) was identified in exon 1 of TPM3 from affected members of the family. The mode of inheritance of our patient is compatible with AD trait. Mutations in ACTA1, TPM3 and TPM2 are reported to cause AD NM. ACTA1 is known to be the most common mutation that accounts for 15–26% while TPM3 accounts for about 3%. There are few reports on intrafamilial phenotypic variability in TPM3 mutations...

Source: Neuromuscular Disorders - September 7, 2013 Category: Neurology Authors: J.S. Park, J.H. Shin, S.J. Hwang, D.S. Kim Source Type: research