Altmann (1955) was the first to describe a congenital aural atresia (CAA) classification, which has been modified over the years (Cremers et al., 1988; Schuknecht, 1989; Jahrsdoerfer et al., 1992). In CAA type I, there is bony or ... Altmann (1955) was the first to describe a congenital aural atresia (CAA) classification, which has been modified over the years (Cremers et al., 1988; Schuknecht, 1989; Jahrsdoerfer et al., 1992). In CAA type I, there is bony or fibrous atresia of the lateral part of the external auditory canal and an almost normal medial part and middle ear. CAA type II is the most frequent type and is characterized by partial or total aplasia of the external auditory canal. CAA type IIA involves an external auditory canal with either complete bony atresia of the medial part or partial aplasia that ends blindly in a fistula leading to a rudimentary tympanic membrane. CAA type IIB is characterized by bony stenosis of the total length of the external auditory canal. CAA type III involves bony atresia of the external auditory canal and a very small or absent middle-ear cavity (summary by Feenstra et al., 2011).
Feenstra et al. (2011) performed SNP-array analysis in affected individuals with syndromic congenital aural atresia from 2 families with 18q22.3-q23 microdeletions and found a 459-kb deletion overlap, a region containing a single known gene, TSHZ1 (614427). Sequencing TSHZ1 ... Feenstra et al. (2011) performed SNP-array analysis in affected individuals with syndromic congenital aural atresia from 2 families with 18q22.3-q23 microdeletions and found a 459-kb deletion overlap, a region containing a single known gene, TSHZ1 (614427). Sequencing TSHZ1 in 6 sporadic and 5 familial patients with an isolated, bilateral form of CAA type IIA and normally shaped pinnae revealed heterozygous loss-of-function mutations in a mother and 2 daughters (614427.0001) and 1 sporadic individual (614427.0002) and his unaffected mother. The mutation-positive individuals had no facial dysmorphism or other features associated with 18q deletion syndrome (see 601808). Whole-gene deletion in the remaining 7 patients was excluded by whole-genome array analysis, and screening the TSHZ1 gene in a cohort of 24 individuals with a unilateral form of CAA type I, IIB, or III, 10 of whom also had mild to severe developmental malformation of the external ears (microtia or anotia), revealed no mutations, suggesting genetic heterogeneity.