NEW X-LINKED MENTAL-RETARDATION SYNDROME WITH THE GENE MAPPED TENTATIVELY IN XP22.3

X-linked mental retardation (XLMR) is genetically heterogeneous and cl inically variable, We describe a new XLMR syndrome of severe mental re tardation and multiple congenital anomalies. Two sisters have (with 3 different partners) 3 severely handicapped sons, In 2 cases, oligohydr amnios and intrauterine growth retardation were noted. Common anomalie s included a square shaped face, high and broad forehead, frontal boss ing, downward slant of palpebral fissures, hypertelorism, epicanthic f olds, long philtrum, thin upper lip, and apparently low-set ears. One boy has bilateral microphthalmos and sclerocornea, and his cousin has atrophy of the optic nerve, All 3 patients are blind and have profound statomotor and mental retardation, seizures, and a grossly abnormal e lectroencephalographic pattern. Additional findings are short stature, delayed bone maturation, hydronephrosis, vesicorenal reflux, cryptorc hidism, clinodactyly of the 5th fingers, and transverse palmar creases , The karyotype is normal (46,XY). Segregation analysis showed perfect coinheritance between the clinical phenotype and alleles at several l oci in Xp22.3, whereas recombinants were identified with marker loci f rom Xp22.2-qter. Analysis of multiple informative meioses suggests tha t the disease locus maps in Xp22.3 distal to DXS16. (C) 1996 Wiley-Lis s, Inc.