Xp21 microdeletion syndrome is associated with variable size Xp21 dele
tions that usually include the glycerol kinase locus. The clinical phe
notypes we studied in this chromosome region include: Xpter - Aland Is
land eye disease (AIED) -adrenal hypoplasia (AH) -glycerol kinase (GKD
) -Duchenne muscular dystrophy (DMD) -retinitis pigmentosa (RP) -ornit
hine transcarbamylase (OTC) -centromere. In a compilation of 18 indivi
duals in 14 families with the AH, GKD, and DMD loci deleted, 17 were m
ale and all were developmentally delayed. In contrast, we report menta
lly retarded female carriers in two Xp21 deletion syndrome families wi
th DMD, GKD, and AH in affected males. In the first family with normal
karyotypes, a submicroscopic deletion was associated with DMD in the
retarded male and with retardation in carrier females. In the second f
amily an X chromosome with a cytogenetically deleted Xp21 distal to th
e OTC and RP genes segregated in the affected male and retarded female
carriers. DNA analysis at the DMD locus verified the cytogenetic find
ings. This report of mental retardation in otherwise asymptomatic fema
le carriers of Xp21 deletion classifies one form of mental retardation
in females.