ACTN2 mutation in a patient with Charcot-Marie-Tooth disease and myopathy

*Correspondence: [e-mail].

Abstract

Case Presentation: R.V.M., 14 years old, male, reports that since early childhood there was a difficulty to walk because of non-progressive low strength in the lower limbs. The patient had a normal cognitive development, but he had his first steps, with support, at the age of 3 years old and without support at the age of 4 years old. He had non consanguineous parents and two members of the family had the same kind of symptoms - maternal aunt and uncle. In the neurological exam there was cavus foot, shoulder and pelvic girdle muscle weakness (MRC grade 3), distal weakness of lower and upper limbs (MRC grade 4), no sensitivity alterations, normal reflexes and cranial nerves evaluation. Electroneuromyography (ENMG) showed chronic sensorimotor polyneuropathy signs compatible with Charcot-Marie-Tooth (CMT) disease. There was also a genetic test which identified heterozygous autosomal dominant ACTN2 gene mutation; there were no other gene mutations identified.

Discussion: ACTN2 gene codes alpha-actinin-2 which is expressed in both skeletal and cardiac muscle. Genetic variants in ACTN2 are associated in the heterozygous state with common inherited cardiac diseases; this mutation is a rare condition, mainly when associated to congenital myopathy. This case report intends to describe a rare mutation in a patient which did not manifestated cardiomyopathy but had a history and neurological exam compatible with a myopathy besides an ENMG compatible with a genetic sensorimotor polyneuropathy as CMT. It is important to spread information about these genetic conditions and their phenotypes to make the diagnosis easier and also to stimulate therapeutic strategies.

Final Comments: ACTN2 genetic mutation is a rare condition that can be associated with cardiomyopathy, congenital myopathy and even polyneuropathy conditions. It is important that neurologists are able to suspect and recognize and disclose this mutation so more research can be stimulated to find therapeutic methods.

Publication History

Article published online:
12 May 2025