X‐linked α‐thalassemia/mental retardation (ATR‐X) syndrome: A new kindred with severe genital anomalies and mild hematologic expression

Abstract

We report a new kindred containing 4 patients with X‐linked α‐thalassemia/mental retardation syndrome ((ATR‐X). Like previously reported ATR‐X patients, these children are all genetic males with severe developmental delay and characteristic facial appearance. The genital anomalies are more severe than in most previous cases and have led to a female sex of rearing for 3 of the 4 patients. The hematologic expression is extremely mild and was not demonstrable on routine hematologic studies including hemoglobin electrophoresis, but the three living patients all had hemoglobin H inclusions on brilliant cresyl blue stained peripheral smears. The combination of skewed X‐inactivation and haplotype analysis at Xq12‐q21.3 confirmed carrier status in the 3 obligate carriers in the kindred and led to identification of an additional carrier. Two other women in the kindred appear to be noncarriers on the basis of normal X‐inactivation and/or inheritance of a different Xq12‐21.3 haplotype. More widespread use of brilliant cresyl blue staining for HbH inclusions in individuals with the facial phenotype of ATR‐X and/or ambiguous genitalia may lead to the identification of more affected patients and improved understanding of the clinical spectrum of ATR‐X.