Deep phenotyping of speech and language skills in individuals with 16p11.2 deletion

Abstract

Recurrent deletions of a ~600-kb region of 16p11.2 have been associated with a highly penetrant form of childhood apraxia of speech (CAS). Yet prior findings have been based on a small, potentially biased sample using retrospectively collected data. We examine the prevalence of CAS in a larger cohort of individuals with 16p11.2 deletion using a prospectively designed assessment battery. The broader speech and language phenotype associated with carrying this deletion was also examined. 55 participants with 16p11.2 deletion (47 children, 8 adults) underwent deep phenotyping to test for the presence of CAS and other speech and language diagnoses. Standardized tests of oral motor functioning, speech production, language, and non-verbal IQ were conducted. The majority of children (77%) and half of adults (50%) met criteria for CAS. Other speech outcomes were observed including articulation or phonological errors (i.e., phonetic and cognitive-linguistic errors, respectively), dysarthria (i.e., neuromuscular speech disorder), minimal verbal output, and even typical speech in some. Receptive and expressive language impairment was present in 73% and 70% of children, respectively. Co-occurring neurodevelopmental conditions (e.g., autism) and non-verbal IQ did not correlate with the presence of CAS. Findings indicate that CAS is highly prevalent in children with 16p11.2 deletion with symptoms persisting into adulthood for many. Yet CAS occurs in the context of a broader speech and language profile and other neurobehavioral deficits. Further research will elucidate specific genetic and neural pathways leading to speech and language deficits in individuals with 16p11.2 deletions, resulting in more targeted speech therapies addressing etiological pathways.

Aetiology of childhood apraxia of speech: A clinical practice update for paediatricians

“…Moderate ID, ASD, poor cognitive and language ability (as great as 2 standard deviation below familial non‐carriers), epilepsy, macrocephaly (apparent by age 2 years), brain abnormalities such as Chiari type 1 malformations or cerebellar ectopia and obesity are associated with 16p11.2 deletion . Several studies have also confirmed the high penetrance of CAS in children with 16p11.2 deletions . Other speech profiles have also been reported in 16p11.2 deletion in addition to CAS, including articulation and phonological disorders, dysarthria, minimal verbal output and even typical speech in some …”

“…Almost all children with KdVS receive a diagnosis of CAS, which is often comorbid with dysarthria and additional articulation and phonological errors . The presence of CAS with co‐occurring speech diagnoses is seen in other genetic conditions, such as Floating‐Harbor syndrome, 7q11.23 duplication syndrome, 16p11.2 deletion and 2p15p16.1 microdeletion as noted above …”

“…A clinical magnetic resonance imaging (MRI) to check for neurological lesions may also be indicated if dysarthria is suspected; children with isolated CAS do not show lesions on routine MRI. However, isolated CAS is rare, and in many cases, children demonstrate one or more of these other developmental speech disorders articulation, phonology dysarthria or even stuttering, alongside CAS …”

“…The discovery that variants of FOXP2 were associated with a rare and monogenic form of CAS catalysed the study of further genes for speech and language disorders. More than 15 years after the FOXP2 discovery, microarray and next‐generation technologies now enable rapid and relatively cost‐efficient genetic testing and have led to a proliferation of further discoveries of gene pathways associated with CAS …”

“…Several studies have also confirmed the high penetrance of CAS in children with 16p11.2 deletions . Other speech profiles have also been reported in 16p11.2 deletion in addition to CAS, including articulation and phonological disorders, dysarthria, minimal verbal output and even typical speech in some …”