Ichthyosis And Male Hypogonadism

In the apparently unique family reported by Lynch et al. (1960), 5 males in 3 generations showed both secondary hypogonadism (associated with low titers of pituitary gonadotropic hormones) and congenital ichthyosis. The authors suggested that close linkage may be responsible for the occurrence of hypogonadism with ichthyosis, a well-known X-linked trait. However, ichthyosis and hypogonadism is listed as a separate mutation since linkage can only be postulated. If indeed the 2 traits are due to 2 linked genes, one can say with 95% confidence that the recombination value is not greater than 20%. The disorder was transmitted by 6 females in whom there was opportunity for crossover. The affected males do not reproduce. (In earlier editions of these catalogs, ichthyosis with male hypogonadism was listed as a distinct X-linked recessive, single gene disorder. With the identification of close linkage of Kallmann syndrome (308700) and X-linked ichthyosis (308100), and the description of deletions leading to the coexistence of these 2 disorders, it becomes a distinct possibility that the affected males in the family reported by Lynch et al. (1960) suffered from a 'contiguous gene syndrome.') In a well-studied Mexican-American kindred with many affected persons, Perrin et al. (1976) reported that anosmia is an additional feature (see 308700) and that linkage with Xg is clearly excluded. Linkage with new markers should be examined in this family: is this family distinct from the families with deletion causing Kallmann syndrome and ichthyosis? Dodinval et al. (1981) described 2 affected brothers.

RUD syndrome is a neurocutaneous disorder characterized by epilepsy, mental retardation, infantilism, congenital ichthyosis, and retinitis pigmentosa. Rud (1927) described a 22-year-old Danish male with ichthyosis, hypogenitalism, epilepsy, polyneuritis, and hyperchromic macrocytic anemia. Two years later, Rud (1929) reported a second case in a 29-year-old female with partial gigantism and diabetes mellitus in addition to ichthyosis and hypogenitalism. Munke et al. (1983) found reports of 28 patients with Rud syndrome. The male:female ratio was 2:1, consistent with some of the cases being instances of an X-linked recessive disorder. Wisniewski et al. (1985) pointed to 2 reports of apparent X-linked inheritance. Their own observations concerned 2 brothers and their mother, who was thought to show heterozygous manifestation. The sons, aged 11 and 10 years, had severe visual impairment from bilateral maculopathy and the other features of RUDS. The mother had decreased visual acuity, increased pigment granularity of both maculae with decreased foveal reflexes, and exaggerated keratosis pilaris of both thighs. (The possibility that this family suffered from a 'contiguous gene syndrome' should be investigated with the search for cytogenetic or molecular genetic evidence of deletion in Xp.) Traupe (1989) provided a useful critical review of 'Rud syndrome.' Einar Rud, a Danish physician, recorded in his 1927 paper that the patient had 15 brothers and sisters and that he was the only one affected. He explicitly stated that the patient was mentally alert ('kvik,' in Danish). The polyneuropathy in the first patient reported by Rud had begun at age 18. The second patient had 'partial gigantism,' whereas his first patient had short stature. The woman was not mentally retarded and did not show any neurologic involvement. Rud (1929) stated that the mother, a brother, and a sister had ichthyosis vulgaris but did not suffer from any of the other symptoms. Traupe (1989) suggested that the designation 'Rud syndrome' be abandoned; from a review of reports he concluded that both the neurologic involvement and the ichthyosis remain ill defined.