In-depth characterisation of a cohort of individuals with missense and loss-of-function variants disrupting FOXP2

Abstract

Background Heterozygous disruptions of FOXP2 were the first identified molecular cause for severe speech disorder: childhood apraxia of speech (CAS), and yet few cases have been reported, limiting knowledge of the condition. Methods Here we phenotyped 28 individuals from 17 families with pathogenic FOXP2-only variants (12 loss-of-function, five missense variants; 14 males; aged 2 to 62 years). Health and development (cognitive, motor, social domains) were examined, including speech and language outcomes with the first cross-linguistic analysis of English and German. Results Speech disorders were prevalent (23/25, 92%) and CAS was most common (22/25, 88%), with similar speech presentations ac..