Abruzzo-Erickson Syndrome

A number sign (#) is used with this entry because of evidence that Abruzzo-Erickson syndrome (ABERS) is caused by mutation in the TBX22 gene (300307) on chromosome Xq21. One such family has been reported.

Clinical Features

Abruzzo and Erickson (1977) reported an apparently 'new' syndrome of cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis expressed variably in 2 brothers, their mother, and a maternal uncle. Davenport et al. (1986) and Metlay et al. (1987) cited this family as a familial instance of CHARGE syndrome (214800). Abruzzo and Erickson (1989) provided follow-up on the 2 brothers of the family who were children at the time of the first report. Like their mother and maternal uncle, neither had choanal atresia. Both had coronal hypospadias but genital development was otherwise normal. The ears were large and protruding, and hearing impairment required a hearing aid. Wide spacing between the second and third fingers as well as unilateral or bilateral radioulnar synostosis was noted in several members of the family. Mental retardation was not present. The manifestations in the mother, who according to the proposed inheritance as an X-linked disorder would be heterozygous, consisted of large ears and flat malar configuration like her sons and brother and wide spacing between the second and third digits as well as unusual rugosity of the palate. The brothers were below the 5th percentile for height at age 19 and 16, respectively.

Molecular Genetics

In the family with an X-linked CHARGE-like syndrome that was originally reported by Abruzzo and Erickson (1977), Pauws et al. (2013) analyzed the candidate gene TBX22 and identified an intronic sequence variant (300307.0011) that segregated with the disease and was not found in the dbSNP database or in 539 control chromosomes. Mutations in TBX22 were also identified in patients with classic X-linked cleft palate phenotypes (CPX; 303400).