Mild phenotype of nemaline myopathy with sleep hypoventilation due to a mutation in the skeletal muscle alpha-actin (ACTA1) gene

Nemaline myopathy is a clinically and genetically heterogeneous condition. The clinical spectrum ranges from severe cases with antenatal or neonatal o nset and early death to late onset cases with only slow progression. Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow cr-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha -actin (ACTA1) on chromosome 1q42. We present a 39-year-old l ady with a mild form of nemaline myopathy, whom we have followed over a per iod of 25 years. She presented at the age of 7 years with symptoms of mild axial and proximal muscle weakness. The overall course was essentially stat ic, but at 36 years, she went into life-threatening respiratory failure, fo r which she is currently treated with night-time ventilation. Muscle biopsi es at 12, 17 and 39 years of age showed typical nemaline rods, particularly in type 1 fibres. Areas with unevenness of oxidative stain were present in the second and third biopsies. The presence of rods and core-like areas wa s confirmed on electron microscopy. There was no detectable alteration in a ctin expression immunocytochemically. A dominant mis sense mutation in the skeletal muscle alpha -actin gene (A CTA I) was found. This case illustrate s the clinical and genetic heterogeneity of nemaline myopathy, and one phen otype of the wide spectrum of severity caused by mutations in the skeletal muscle alpha -actin (ACTA1) gene, In addition, it shows the diversity of pa thological features that can occur in congenital myopathies due to mutation s in the same gene. (C) 2001 Elsevier Science B.V. All rights reserved.