PNPT1 is a mitochondrial RNA transport protein that has been linked to two discrete phenotypes, namely isolated sensorineural hearing loss (OMIM 614934) and combined oxidative phosphorylation deficiency (OMIM 614932). The latter has been described in multiple families presenting with complex neurologic manifestations in childhood. We describe adult siblings with biallelic PNPT1 variants identified through WES who presented with isolated severe congenital sensorineural hearing loss (SNHL). In their 40s, they each developed and then followed a nearly identical neurodegenerative course with ataxia, dystonia, and cognitive decline. Now in their 50s and 60s, all have developed the additional features of optic nerve atrophy, spasticity, and incontinence. The natural history of the condition in this family may suggest that the individuals previously reported as having isolated SNHL may be at risk of developing multisystem disease in late adulthood, and that PNPT1-related disorders may constitute a spectrum rather than distinct phenotypes.
Keywords: autosomal recessive; congenital sensorineural hearing loss; mitochondrial disorders; next generation sequencing; rare diseases.
© 2018 Wiley Periodicals, Inc.