CLCN4-Related Neurodevelopmental Condition: Characterization of Speech and Language Abilities.

Abstract

Speech and language difficulties are a core feature of the CLCN4-related neurodevelopmental condition, but these have not been well described. Here we systematically phenotype speech and language in 13 participants (10 female, aged 1 year 10 months-41 years 10 months) with pathogenic CLCN4 variants (12 missense de novo, 1 premature stop codon maternal inheritance). Speech, language, and augmentative and alternative communication (AAC) methods were examined. Expressive and receptive language conditions were highly penetrant (12/13, 92%). Eight participants were minimally verbal but used a range of low (e.g., gesture) and high-tech (e.g., device) methods to communicate. Verbal participants had both apraxia and dysarthria, characterized by inconsistent productions, sound distortions, resonance changes, and persistent voice quality and prosodic errors. Participants were all intentional communicators, being motivated to get their message across. A discrepancy was present, however, between the ability to express basic needs versus demonstrate social skills or social exchanges. Data highlight the potential for the implementation of tailored AAC to enhance functional social participation and extend language abilities. Communication difficulties are pervasive in CLCN4-related neurodevelopmental condition. Data emphasize the importance of individualized and timely speech therapy, and particularly the introduction of AAC to optimize language growth.