New X-linked mental retardation syndrome with the gene mapped tentatively in Xp22.3

Abstract

X‐linked mental retardation (XLMR) is genetically heterogeneous and clinically variable. We describe a new XLMR syndrome of severe mental retardation and multiple congenital anomalies. Two sisters have (with 3 different partners) 3 severely handicapped sons. In 2 cases, oligohydramnios and intrauterine growth retardation were noted. Common anomalies included a square‐shaped face, high and broad forehead, frontal bossing, downward slant of palpebral fissures, hypertelorism, epicanthic folds, 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 electroencephalographic pattern. Additional findings are short stature, delayed bone maturation, hydronephrosis, vesicorenal reflux, cryptorchidism, 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 loci in Xp22.3, whereas recombinants were identified with marker loci from Xp22.2‐qter. Analysis of multiple informative meioses suggests that the disease locus maps in Xp22.3 distal to DXS16. © 1996 Wiley‐Liss, Inc.

Further delineation of Wittwer syndrome and refinement of the mapping region

“…Furthermore, urogenital anomalies, malrotation of the gut, and abnormal two segmentation of the lungs have been described. In addition, to the clinical findings described by Wittwer et al [1996] skeletal changes seem to be typical. Radiographic examination revealed dysplastic lesions in the proximal femora (Fig.…”

“…In III2 a recombination event occurred between DXS8095 and DXYS231X. In view of the results of linkage analysis performed by Wittwer et al [1996] the locus maps in Xp22.3 into the region between DXS8095 and DXS7108. Therefore, the mapping interval can be narrowed to a region of 3.9–6.1 Mb.…”

“…Wittwer et al [1996] described a novel X‐linked syndrome mainly characterized by severe mental retardation, intrauterine and postnatal growth retardation, blindness, hearing loss, epilepsy, and dysmorphic features. To this spectrum of symptoms skeletal anomalies have to be added.…”

“…Three main regions involved in MRXS/MRX could be delineated [Lubs et al, 1996]: the distal regions of the short (pter‐p22.1) and long (q27‐qter) arms, and the pericentromeric region (p11‐q21). In 1996, Wittwer et al described a new X‐linked mental retardation syndrome. We had the opportunity to reexamine the family and to perform a more extensive linkage analysis leading to a refinement of the mapping region in Xp22.3.…”

“… Abstract In 1996, Wittwer et al described a XLMR‐syndrome mapping in Xp22.3. This family was reexamined.…”