Phenotypic overlap between cardioacrofacial dysplasia-2 and oral-facial-digital syndrome

Eur J Med Genet. 2022 Apr 16:104512. doi: 10.1016/j.ejmg.2022.104512. Online ahead of print.ABSTRACTOral-facial digital (OFD) syndrome is characterized by abnormalities of the face (hypertelorism and low set-ears), oral cavity (multiple frenula, lingual hamartoma, or lobulated tongue) and extremities (postaxial polydactyly). At least 19 genes have been implicated in the development of OFD syndrome. Herein, we report the case a 13-year-old patient with atrioventricular septal defect, moderate intellectual disability, epilepsy, and features of OFD, including multiple oral frenula, and postaxial polydactyly of the hands and feet. The patient had a de novo heterozygous variant in PRKACB: chr1(GRCh37):g.84700915T > C, c.1124T > C (NM_182948.4), p.(Phe375Ser). To date, four patients with pathogenic monoallelic variants in PRKACB have been reported, and the condition associated with these variants is referred to as Cardioacrofacial dysplasia-2 (CAFD2, MIM619143). Previously reported features of this condition include congenital heart disease (e.g., atrioventricular septal defect) and postaxial polydactyly, and two of the patients had multiple oral frenula. We suggest that a significant phenotypic overlap exists between CAFD2 and OFD syndrome, in that these patients especially share the features of postaxial polydactyly and multiple oral frenula. The phenotypic similarity between patients with CAFD2 and classic OFD syndrome with an OFD1 variant might be explained by the recent ...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Source Type: research