Does IARS2 deficiency cause an intrinsic disorder of bone development (skeletal dysplasia) or are the reported skeletal changes secondary to growth hormone deficiency and neuromuscular involvement?

Schwartzentruber et al. [2014] and Deal et al. [2012] recently reported three patients with mitochondrial isoleucyl aminoacyl-tRNA synthetase (IARS2; MIM #612801) variants resulting in cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia. Acronymous titles are a familiar and useful way to remember the characteristic phenotypes of patients with mitochondrial disorders, exemplified by the best known mitochondrial phenotype, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes [Pavlakis et al., 1984].