Phoniatric, audiological, orodental and speech problems in a boy with cardio-facio-cutaneous syndrome type 3 (Cfc 3) due to a pathogenic variant in map2k1 – case study

Abstract

Cardio-facio-cutaneous syndrome 3 (CFC3) due to variants in MAP2K1 is a rare genetic disorder manifested mainly by short stature, facial dysmorphism, abnormalities of the cardiovascular system, skin changes, and intellectual disability. The aim of the study is the evaluation of the occurrence of pathological changes in the upper respiratory tract, orthodontic disorders, as well as voice, speech and hearing abnormalities in an 11-year-old boy with CFC3 syndrome. The lack of detailed diagnostics of speech, voice and hearing disorders, as well as the degree of their severity was an inspiration to undertake research in this field. Pathological changes in face, oral cavity, upper respiratory tract (nose, naso-pharynx, larynx), and hearing organ, as well as voice and speech quality, were assessed in an 11-year-old boy with CFC3 syndrome. Pathologies of the upper respiratory tract (adenoid hypertrophy, narrowing of the nasal passages) and laryngeal asymmetry were found without significant changes in voice quality in the acoustic examination, except for the voice timbre change confirmed in narrowband spectrography. Complex audiological assessment confirmed the existence of bilateral sensorineural hearing loss. Speech pathology assessment revealed abnormalities in the structure of articulation organ, its decreased motor efficiency, impreci-sion, reduced coordination, as well as the presence of autistic features. Exome sequencing showed the heterozygous variant c.371C>T (p.Pro124Leu) in the MAP2K1 gene, previously described as pathogenic, thus supporting a causative relevance. Phoniatric, audiological, orodental and speech problems should be considered as features of cardio-facio-cutaneous syndrome type 3 (CFC 3) phenotype due to a pathogenic variant in MAP2K1.