A unique X-linked syndrome characterized by congenital deafness, mild dysmorphic features, mid-phalangeal hypoplasia, hernias, and late-onset pancytopenia

Abstract

Three males ranging from 54 to 12 years of age in one kindred were evaluated for a syndrome associated with hearing loss at the request of a female relative desiring preconception counseling. Review of their pedigree was consistent with X-linked recessive inheritance as the males spanned 3 generations and were related through female relatives. No consanguinity was noted. Features in 3 of 3 of the affected males included bilateral congenital severe-profound sensorineural hearing loss (SNHL); mild facial dysmorphisms with telecanthus and unusual ears; mild to moderate mental retardation; telangiectasis; umbilical hernias; dermatoglyphics characterized by a high number of arches; small hypoplastic nipples; and shortening of the mid-phalanges. In addition, the two older males (ages 31 and 54) had microcephaly, short stature and pancytopenia, which was most severe in the 54-year-old man. Both men had normal cytogenetic studies. The clinical course of the 54 year old man was complicated by hypothyroidism diagnosed at 16 years of age, chronic glomerular nephritis diagnosed at 50 years of age resulting in renal failure, and a cataract. Peripheral blood chromosome analysis of the 12-year-old boy revealed a mosaic karyotype of 46XY/45X at birth. He had additional urogenital abnormalities consisting of a bifid scrotum, small testicles and phallus, and absence of the vas deferens and epididymis. Review of the literature, search of the dysmorphology databases, and curbside consultation at a previous American Society of Human Genetics Meeting did not suggest a recognized syndrome. Thus, it seems likely that this is a new X-linked syndrome of SNHL associated with mild dysmorphic features, mid-phalangeal hypoplasia, umbilical hernias, and late-onset pancytopenia. The underlying molecular basis of this syndrome is unclear but it is hoped that analysis of candidate deafness genes on the X chromosome wilt be revealing.