Speech and language phenotyping in children with cleft lip and/or palate and their unaffected relatives

© 2019 Dr. Jessica Oiuchee BoyceBackground: Cleft lip and/or palate (CL/P) is one of the most common birth defects. Non-syndromic CL/Ps make up 70% of cases and are associated with complex phenotypes, challenging accurate clinical diagnosis and prognostication. Children with CL/P may have impaired language, or disordered speech associated with velopharyngeal insufficiency (VPI). Existing research defines several sub-clinical cleft phenotypes, identified from unaffected relatives, that may advance clinical knowledge and contribute to our understanding of genetic aetiology. VPI has long been suggested as a sub-clinical phenotype, but only recently studied. Aims: Broad aims were: (1) to systematically review the literature exploring speech and language skills of children with submucous cleft palate (SMCP); (2) to describe the speech and language characteristics of probands with different cleft types; and (3) to provide sub-clinical speech phenotyping for clinically ‘unaffected’ relatives of probands with cleft lip with or without palate (CL±P). Methods: (1) Five databases were comprehensively searched. Included studies reported speech or language profiles of individuals with SMCP. (2) Participants with clefts (overt CL/P n = 37; SMCP n = 15) were recruited from the cleft registry at the Royal Children’s Hospital (RCH), Melbourne, Australia. Language data from non-cleft participants was obtained from the Early Language in Victoria Study (n = 129). (3) Probands with overt clefts were identified from the RCH cleft registry, and their unaffected family members were contacted for participation (n = 189). Non-cleft participants were recruited from Melbourne, Australia (n = 207). All participants had non-syndromic diagnoses with no medical conditions likely to impact communication. Non-cleft participants also had no known family history of clefting. Speech was assessed perceptually, using common clinical tools, and instrumentally with the Nasometer. Language was assessed using the Clinical Evaluation of Language Fundamentals, Fourth Edition and the Children’s Communication Checklist, Second Edition. Non-verbal IQ was screened using the Weschler Abbreviated Scale of Intelligence, Second Edition. Results: (1) Children with SMCP may present with speech difficulties similar to those experienced by individuals with overt clefts. There is a dearth of literature exploring the language abilities of this population. (2) Children with overt clefts had language skills that were comparable to their non-cleft peers. Those with SMCP had variable speech and language performance, with overall poorer language than those with or without overt clefts. Participants with SMCP and poor language also had low non-verbal IQ. (3) Speech in unaffected relatives was not significantly different to that of a matched non-cleft cohort. Discussion & conclusion: Detailed phenotyping from this thesis highlights a diversity in communication profiles between and within groups of individuals with different cleft types. Results emphasise the importance of individualised assessment, where clinicians do not make assumptions based on a child’s cleft. Conclusions from the SMCP study suggest that other unidentified neurodevelopmental disorders may be present, questioning the accuracy of truly ‘non-syndromic’ diagnoses. Data from the third aim suggest that VPI is not a significant sub-clinical phenotype of non-syndromic CL±P and thus may not warrant further exploration in familial genetic investigations. Outcomes contribute to the complex CL/P phenotyping and genotyping landscape