Nemaline Rod/Cap Myopathy Due to Novel Homozygous Mutations: The First Report from South Asia and Comprehensive Literature Review.

BACKGROUND AND PURPOSE

Pathogenic variants in the myopalladin gene () are known to cause mildly progressive nemaline/cap myopathy. Only nine cases have been reported in the English literature.

METHODS

A detailed evaluation was conducted of the clinical, muscle magnetic resonance imaging (MRI), and genetic findings of two unrelated adults with -related cap myopathy. Genetic analysis was performed using whole-exome sequencing. MRI was performed on a 1.5-T device in patient 1.

RESULTS

Two unrelated adults born to consanguineous parents, a 28-year-old male and a 23-year-old female, were diagnosed with pathogenic variants in that cause cap myopathy. Both patients presented with early-onset, insidiously progressive, and minimally disabling proximodistal weakness with mild ptosis, facial weakness, and bulbar symptoms. Patient 1 had a prominent foot drop from the onset. Both patients were followed up at age 30 years, at which point serum creatine kinase concentrations were minimally elevated. There were no cardiac symptoms; electrocardiograms and two-dimensional echocardiograms were normal in both patients. Muscle MRI revealed preferential involvement of the glutei, posterior thigh muscles, and anterior leg muscles. Whole-exome sequencing revealed significant homozygous splice-site variants in both of the probands, affecting intron 10 of : c.1973+1G>C (patient 1) and c.1974-2A>C (patient 2).

CONCLUSIONS

This study elaborates on two patients with homozygous pathogenic variants, presenting as slowly progressive congenital myopathy. These patients are only the tenth and eleventh cases reported in the English literature, and the first from South Asia. The clinical phenotype reiterates the mild form of nemaline rod/cap myopathy. A comprehensive literature review is presented.