Unraveling the Etiology of Childhood Hypotonia Using Exome Sequencing

This cohort study of 48 unrelated probands with rare monogenic childhood hypotonia was designed to assess the clinical presentations, spectrum of disorders, and utility of exome sequencing in selected cases where preliminary genetic tests did not sufficiently explain the etiology. Clinically 56.3% of the cases appeared to be of peripheral hypotonia, 33.3% cases were of central hypotonia, and remaining 10.4% were mixed hypotonia cases. Exome sequencing was able to provide a diagnosis in 52.1% cases in the entire cohort of rare monogenic childhood hypotonia. Majority (41.6%) of the probands had a clinical diagnosis of congenital myopathy/muscular dystrophy in the cohort of which 60% arrived at a molecular diagnosis. LMNA-related and LAMA2-related congenital muscular dystrophies were the most common genes identified in the cohort. We also report 12 novel variants and provide illustrative rare phenotypes for better delineation of specific disorders.