STAC3-Associated Congenital Myopathy in a Boy of Turkish Ancestry with Severe Scoliosis and Early-Onset Respiratory Insufficiency

Background/Purpose: Native American myopathy (NAM) is an autosomal recessive congenital myopathy, up to now exclusively described in Lumbee Indians who harbor one single homozygous mutation (c.1046G>C, pW284S) in the STAC3 gene. We report the first non-Amerindian patient of Turkish ancestry, being compound heterozygous for two novel mutations in the STAC3 gene.

Methods: Clinical examination, muscle MRI of lower extremities, and muscle biopsy were performed. Next-generation sequencing (NGS) panel analysis of 105 genes for different forms of congenital myopathies and muscular dystrophies were conducted in the index patient.

Results: Our patient of Turkish ancestry is the first non-Amerindian patient. NGS revealed two novel compound heterozygous mutations (c.862A>T and c.432+4A>T) in the STAC3 gene. Like other patients diseased with NAM, our patient showed mild dysmorphic features, a proximal accentuated muscle weakness with facial involvement, progressive scoliosis, and early ventilatory failure with sustained ambulation. MRI showed bilaterally symmetric fatty degeneration of all muscles examined. Unspecific myopathic changes and subsarcolemmal lipid droplets were disclosed in muscle biopsy.

Conclusion: This case shows that NAM should also be considered in non-Amerindian patients with congenital myopathy. Stac3 mutations should be taken into account as a potential cause of malignant hyperthermia.