X-linked alpha-thalassemia/mental retardation (ATR-X) syndrome: a new kindred with severe genital anomalies and mild hematologic expression.
We report a new kindred containing 4 patients with X-linked alpha-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.
McPherson
E W
EW
University of Pittsburgh, Pennsylvania, USA.
Clemens
M M
MM
Gibbons
R J
RJ
Higgs
D R
DR
D000015:Abnormalities, Multiple / Q000235:genetics; D002675:Child, Preschool; D012734:Disorders of Sex Development / Q000235:genetics*; D004303:Dosage Compensation, Genetic; D005145:Face / Q000002:abnormalities; D005260:Female; D008040:Genetic Linkage; D006447:Hemoglobin H / Q000032:analysis; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D014960:X Chromosome; D017085:alpha-Thalassemia / Q000235:genetics*
D006447:Hemoglobin H