Objective: 18q deletion syndrome is a multiple-anomaly mental retardation syndrome associated with congenital aural atresia. The purpose of this study was to determine the frequency of the congenital aural atresia phenotype in 18q deletion syndrome patients and to delineate a potential critical region for congenital aural atresia at the 18q22.3-18q23 region.
Study design and patients: The study describes one 18q deletion syndrome clinical report (Patient 15) with an overview of 19 other selected 18q deletion syndrome patients presenting congenital aural atresia from 18 published articles and one presented poster on 18q deletion syndrome.
Results: Our investigation, together with the results of published 18q deletion syndrome reports, shows that the average frequency of congenital aural atresia is approximately 52%. A combination of three 18q deletion syndrome probands defines a chromosomal deletion site for congenital aural atresia at 18q22.3-18q23 in the region between markers D18S489 and D18S554. These polymorphic markers outline a putative critical interval of approximately 2.3 Mb, including the genes ZNF407, ZADH2, SDCCAG33, ZNF516, FLJ44881, ZNF236, MBP-Golli, and GALR1. The haploinsufficiency of these genes is suggested to be a primary cause of congenital aural atresia phenotype in 18q deletion syndrome individuals.
Conclusion: Congenital aural atresia is a relevant diagnostic clue and a major recognizable feature of 18q deletion syndrome. Early diagnosis of 18q deletion syndrome may enable application of hearing aids. Knockout studies on the congenital aural atresia mouse gene homolog may add further insight into the genes responsible for this condition.