An adult case of Koolen-de Vries syndrome - Is post-lingual sensorineural hearing loss less infrequent than commonly assumed?

Spinelli, A. (2024). An adult case of Koolen-de Vries syndrome - Is post-lingual sensorineural hearing loss less infrequent than commonly assumed? (Version 1) [DataSet]. GestaltMatcher Database.

A 42-year-old man was evaluated for a recently-discovered bilateral moderate-to-severe sensorineural hearing loss (SNHL), with a drop in the high-frequency range, in the context of an undiagnosed syndromic neurodevelopmental disorder (poor suck and infantile hypotonia, delayed psychomotor development; intellectual disability - no less than moderate; distinctive face; bilateral cryptorchidism (treated surgically at age 10); moderate-severe scoliosis; increased arm-span-to-standing-height ratio; significant lower limb length discrepancy; anterior mitral leaflet prolapse; high-arched and narrow palate; agenesis of two permanent maxillary incisors; childhood-onset bilateral cataracts and glaucoma; myopia - mild to severe). Facial gestalt was highly indicative of Koolen-de Vries syndrome. WES analysis showed a heterozygous de novo splicing variant in KANSL1. Conversely, a virtual panel for hearing loss (OtoSCOPE/PanelApp gene list) did not identify any P/LP variants (indirect CN analysis was based on short-read sequencing data only, no quantitative testing was performed for STRC, OTOA, SLC26A4, USH2A genes). In conclusion, while at the moment SNHL is considered an uncommon finding in individuals with KdVS irrespective of their age (GeneReviews, 2023), this case raises the possibility that SNHL might be a late-onset complication quite frequent in adulthood and rare before young adulthood, in line with observations from a recent case series (Amenta et al., JMG, 2022). Audiograms may mimic those of age-related hearing impairment. A systematic collection of natural history data will be needed to confirm this preliminary hypothesis.