Search for a genetic cause in children with unilateral isolated microtia and congenital aural atresia

Purpose: Microtia describes a spectrum of auricular malformations ranging from mild dysplasia to anotia. A vast majority of microtia patients demonstrate congenital aural atresia (CAA). Isolated microtia has a right ear predominance (58-61%) and is more common in the male sex. Isolated microtia is a multifactorial condition involving genetic and environmental causes. The aim of this study is to describe the phenotype of children with unilateral isolated microtia and CAA, and to search for a common genetic cause trough DNA analysis.

Methods: Phenotyping included a complete clinical examination. Description on the degree of auricular malformation (Weerda classification-Weerda 1988), assessment for hemifacial microsomia and age-appropriate audiometric testing were documented. Computerized tomography of the temporal bone with 3-D rendering provided a histopathological classification (HEAR classification-Declau et al. 1999). Genetic testing was carried out by single nucleotide polymorphism (SNP) microarray.

Results: Complete data are available for 44 children (50% was younger than 33 days at presentation; 59.1% boys; 72.7% right ear). Type III microtia was present in 28 patients. Type 2b CAA existed in 32 patients. All patients had a normal hearing at the non-affected side. Genome wide deletion duplication analysis using microarray did not reveal any pathological copy number variant (CNV) that could explain the phenotype.

Conclusions: Type III microtia (peanut-shell type) in combination with a type 2b CAA was the most common phenotype, present in 23 of 44 (52.3%) patients with isolated unilateral microtia. No abnormalities could be found by copy number variant (CNV) analysis. Whole exome sequencing in a larger sample with a similar phenotype may represent a future diagnostic approach.