Young Syndrome

Description

Young syndrome is characterized by chronic sinopulmonary infections, persistent azoospermia, and normal spermatogenesis (Handelsman et al., 1984).

Clinical Features

Young, a urologist, wrote as follows in 1970: 'Recently, I have become aware of a genetic linkage between bronchiectasis, possibly due to congenital cystic disease of the lung, and failure of the vasa deferentia to join together as an epididymis. In consecutive operations from 1st October 1968 to 1st June 1970, of fifty-two men operated on for azoospermia twenty-eight had a defect of their lungs; eighteen gave a history of bronchitis from childhood, seven others had been diagnosed as bronchiectasis, and three had a lobectomy for bronchiectasis: 54% had had a defect in their lungs. I call it the Barry-Perkins-Young syndrome. A similar genetic linkage is present in Saanen goats which have azoospermia and no horns (Young, 1970).' Hendry et al. (1978) drew attention to the Young syndrome.

Handelsman et al. (1984) studied 29 affected men. They had only mildly impaired respiratory function and normal spermatogenesis. The azoospermia was attributed to obstruction of the epididymis by inspissated secretions. The sperm are normal in Young syndrome. Pregnancy had occurred in 5 couples; in 3, paternity was documented by genotyping. Thus, improved microsurgery might restore fertility. Handelsman et al. (1984) suggested that Young syndrome is as common as Klinefelter syndrome (actually they stated that in their experience it 'has at least twice the prevalence of Klinefelter's syndrome') and is therefore a common cause of both chronic sinopulmonary infection and azoospermia. Handelsman et al. (1984) noted that male infertility and chronic sinopulmonary infections occur also in immotile-cilia syndrome (244400) and in cystic fibrosis (219700), but suggested that those disorders are rarer than Young syndrome.

Handelsman et al. (1984) suggested that the epididymal obstruction may be progressive and not become complete until years after puberty. Unlike the findings in men with congenital absence of the vas deferens (CBAVD; 277180) or vasectomized men, 60 to 80% of whom acquire and maintain high titers of sperm antibodies, such does not occur in Young syndrome.

Khan et al. (1987) described 2 cases, one in a Yemeni man and the other in a Somalian man. Both presented in their early twenties with a history of chronic sinopulmonary infections and both were married but had primary infertility with normal libido, potency, puberty, and shaving frequency. They had normal-sized gonads with distended epididymal heads. The epididymis has been found to be normal (Hendry et al., 1978) in patients with Young syndrome. Furthermore, the spermatozoa aspirated from epididymal heads are normal, as are the cilia in bronchial biopsy specimens (Le Lannou et al., 1981). Hughes et al. (1987) emphasized the potentially correctable nature of this disorder with microsurgical vasoepididymostomy.

Inheritance

Because of occurrence in brothers but lack of vertical transmission, Handelsman et al. (1984) supported autosomal recessive inheritance. There had, it seemed, been no evidence of 'oblique transmission' (involvement of uncles and nephews) to support X-linked recessive inheritance. The apparently high gene frequency on the assumption of autosomal recessive inheritance will require explanation.

Molecular Genetics

Young syndrome is a cause of male infertility as is also congenital bilateral absence of the vas deferens arising from mutations in the CFTR gene (602421). In general, males with cystic fibrosis (CF; 219700) have absence of the vas deferens. Hirsh et al. (1993) found that 2 of 7 men ascertained among couples referred for assisted conception where the male partner had Young syndrome were carriers of the delF508 mutation (602421.0001), the most common CF mutation in northern Europe.

Because of some similarities between Young syndrome, CF, and CBAVD, Friedman et al. (1995) evaluated 13 patients with Young syndrome, including screening for more than 30 different mutations within the CFTR gene. Only 1 of the 26 Young syndrome chromosomes carried a recognized CF mutation, delF508. The incidence did not differ significantly from the expected carrier frequency population. They concluded that typical Young syndrome is not associated with CFTR mutations. Similarly, Le Lannou et al. (1995) screened 2 groups of infertile men with obstructive azoospermia for CF gene mutations. The first group was composed of 26 patients with CBAVD; the second group was composed of 12 patients with obstructive azoospermia associated with chronic suppurating respiratory disease (Young syndrome). Of the group with CAVD, 77% showed at least one mutation in the CFTR gene. In Young syndrome, no CF mutations were detected.