New X-linked mental retardation (XLMR) syndrome with distinct facial appearance and growth retardation.

We report on 2 brothers and their nephew with an apparently new X-linked mental retardation (XLMR) syndrome characterized by a distinct facial appearance, growth retardation, and severe mental retardation. The facial traits included triangular shape; bifrontal narrowness; malar flatness; blepharophimosis; very deeply set eyes; epicanthus inversus; bulbous nose; low hairline; low-set, deeply cupped, and protruding ears; short ill-defined philtrum; and thin tented upper lip. These facial anomalies are particularly striking and recognizable even at birth. The boys were small for gestational age and remained below -2 SD in growth parameters. With age, large joint contractures developed. Pectus excavatum was apparent at birth but became more obvious with age. Global developmental delay was evident in infancy. The brothers were nonverbal while their nephew spoke simple words. Optic atrophy, esotropia, nystagmus, and spastic diplegia were evident. They were self-abusive, hyperactive, and poorly coordinated. CT scans demonstrated atrophic hydrocephalus. No EEG abnormalities were detected. Karyotypes were 46,XY and fragile X negative. Routine chemistries; amino, organic, and uronic acids; oligosaccharides; lysosomal enzymes; and very long chain fatty acids were normal. Remarkable phenotypic similarity between these brothers and their nephew and lack of manifestations in their mothers makes X-linked recessive inheritance likely. This syndrome, which does not appear to have been reported previously, adds to the delineation of XLMR.