CONGENITAL MYOPATHIES – NEMALINE MYOPATHIES: EP.37 ACTA1 congenital myopathy: clinical and genetic spectrum of 5 chilean newborns

Abstract

Congenital myopathy related with ACTA1 mutation may produce very severe and less severe clinical pictures with different genetic and histopathologic features. We describe clinical and histopathologic features of 5 newborns (two girls) studied between 2013 and 2020 in Clinica Alemana de Santiago and Hospital Luis Calvo Mackenna. Genetic analysis was performed in Hospital Bambino Gesú and Invitae (commercial laboratory USA). The first patient studied (2013) was a girl with fetal akinesia syndrome. She was ventilator dependent since birth, had no movements and presented distal contractures. Histopathology showed myopathic unspecific findings. She died at 6 months of age. Genetic study showed an ACTA 1 de novo mutation. Patients 2 and 3 are boys with neonatal hypotonia, weakness, facial diplegia and mild transient respiratory problems. Patients 2 and 3 had muscle biopsy with cytoplasmic rods. Both showed progressive motor improvement. Genetic analysis showed ACTA1 mutation de novo (patient 2) and autosomal recessive (patient 3). Patient 4 was a girl who showed severe generalized muscular weakness, facial diplegia, ventilatory dependence and progressive dilated myocardiopathy. Muscle biopsy showed type 1 fiber atrophy. Genetic study showed ACTA 1 de novo mutation. She died at 5 months of age. Patient 5, a 1-year-old boy with severe hypotonia and weakness, facial diplegia eyelid ptosis and mechanical ventilator dependent since birth. Muscle biopsy showed unspecific myopathic findings and genetic study detected ACTA 1 de novo mutation. We conclude that de novo ACTA1 mutation correlates with more severe and even fatal outcome (3 out of 4 of our patients) and AR ACTA1 mutation correlates with a more benign outcome (1 of our patients). Finally, muscle histopathology with rods seems to predict a less severe outcome but this is too small a series to validate this hypothesis.