X-linked mental retardation syndrome with seizures, hypogammaglobulinemia,and progressive gait disturbance is regionally mapped between Xq21.33 and Xq23

We identified a family with three males in two generations with moderate me ntal retardation. The two oldest were first cousins whose mothers were sist ers. The third affected was a grandson through a daughter of one of the sis ters, strongly suggesting X-linked inheritance. The affected males had prom inent glabella, synophrys, prognathism, generalized hirsutism, and bilatera l single palmar creases. All developed seizures in childhood. The two oldes t have had a slow deterioration in neurological status with poor gait and b alance and progressive weakness. No deterioration in their mental status ha s been observed. The oldest had cerebellar atrophy confirmed on computed to mography and magnetic resonance imaging scans of the brain and prolonged ne rve conduction velocity. Two of the males had hypogammaglobulinemia (IgA de ficient). Two-point linkage analysis using 27 microsatellite markers on the X chromosome resulted in a maximum LOD score of 2.23 at theta = 0 for locu s DSX101, Recombination was observed at locus DSX1170 in Xq21.33 and locus DXS8067 in Xq23, We conclude that this family represents an X-linked disord er associated with a recognizable phenotype, progressive neurological deter ioration, and variable hypogammaglobulinemia. The gene appears to lie betwe en Xq21.33 and Xq23. Am. J. Med. Genet. 85:255-262, 1999. (C) 1999 Wiley-Li ss, Inc.