Hearing, Speech, Language, and Communicative Participation in Patients With Apert Syndrome: Analysis of Correlation With Fibroblast Growth Factor Receptor 2 Mutation

Abstract

Apert syndrome (AS) is caused by the heterozygous presence of 1 of 2 specific missense mutations of the fibroblast growth factor receptor 2 (FGFR2) gene. The 2 adjacent substitutions, designated p.Ser252Trp (S252W) and p.Pro253Arg (P253R), account for more than 98% of cases. Previous research has identified elevated hearing difficulties and incidence of cleft palate in this population. However, the influence of FGFR2 genotype on the speech, language, and communicative participation of children with AS has yet to be examined. Methods: A retrospective case note analysis was completed for all patients with a genetically-confirmed Apert mutation who attended the Oxford Craniofacial Unit over a 43-year period (1978-2020). Medical records were analyzed for speech, language, hearing, and communication data in detail. The therapy outcome measures, based on the World Health Organization International Classification of Functioning, Disability, and Health was used to classify patient's communicative participation. Results: The authors identified 55 AS patients with geneticallyconfirmed mutation of the FGFR2 gene. One patient with a S252F mutation was excluded. There were 31 patients with the S252W mutation (male ¼ 14; female ¼ 17), age range of last hearing assessment (1-18 years), 64% (18/28) of patients had a cleft palate (including bifid uvula), 15 patients had conductive hearing loss, 1 patient had mixed hearing loss, 18 had otitis media with effusion (4 of whom had a cleft palate); 88% (21/24) of patients had receptive language difficulties, 88% (22/25) of patients had expressive language difficulties, 96% (27/28) of patients had a speech sound disorder. There were 23 patients with the P253R mutation (male ¼ 13; female ¼ 10); age range of last hearing assessment (1-13 years), 35% (8/23) patients had a cleft palate (including bifid uvula), 14 patients had a conductive hearing loss, 17 had otitis media with effusion (2 of whom had a cleft palate). Results indicated that 85% (17/20) of patients had receptive language difficulties, 80% (16/20) had expressive language difficulties, 100% (21/21) had a speech sound disorder. The S252W mutation was significantly-associated with the presence of cleft palate (including bifid uvula) (P ¼ 0.05).Data about the cumulative impact of all of these factors for communicative participation using the therapy outcome measures were available for 47 patients: (30 S252W; 17 P253R). Patients with a S252W mutation had significantly more severe difficulties with communicative participation when compared to individuals with a P253R mutation (P ¼ 0.0005) Cochran-Armitage trend test. Conclusions: Speech, language, communicative participation, and hearing difficulties are pervasive in patients with AS. The severity and functional impact of these difficulties are magnified in patients with the S252W mutation. Results reinforce the importance of considering patients with AS according to genotype.

Speech and Language Development, Hearing, and Feeding in Patients With Genetically Confirmed Crouzon Syndrome With Acanthosis Nigricans: A 36-Year Longitudinal Retrospective Review of Patients at the Oxford Craniofacial Unit

“…Previous research has highlighted the implication of oral structural differences for speech sound production in patients with syndromic craniosynostosis 43–46 . This was reflected in the current study, with the well-documented midface hypoplasia and resultant occlusal differences leading to a speech sound disorder in 50% (n = 3/6) of patients.…”

“…Previous research has highlighted the implication of oral structural differences for speech sound production in patients with syndromic craniosynostosis. [43][44][45][46] This was reflected in the current study, with the well-documented midface hypoplasia and resultant occlusal differences leading to a speech sound disorder in 50% (n = 3/6) of patients. The majority of speech sound errors were obligatory, meaning that these errors cannot be remediated with speech therapy due to oral structural differences.…”

Cleft Palate in Apert Syndrome

“…Genotype–phenotype correlations in Apert syndrome have been studied. Although these correlations are variable, cleft palate is associated more commonly with the S252W variant than P253R in multiple studies comparing subgroups defined by these two variants in FGFR2 [ 16 , 17 , 78 , 79 , 80 , 81 ]. Cleft palate is present in approximately 60% of patients with the S252W variant and 15% of patients with the P253R variant ( Table 3 ), suggesting this genotype–phenotype correlation in Apert syndrome.…”