Hypogonadotrophic hypogonadism with hyposmia, X-linked ichthyosis, and renal malformation syndrome.

Objective: The aim of this study was the endocrinological, enzymatic, and genetic evaluation of a family with a complex syndrome associating hypogonadotrophic hypogonadism with hyposmia, X-linked ichthyosis and renal malformation.

Design: Hypothalamic-pituitary-testicular function, olfaction, steroid sulphatase activity, and morphological renal studies were assessed. DNA molecular analyses were carried out in all the patients.

Patients: Two brothers and their maternal uncle showed the clinical picture of congenital ichthyosis, hypogonadism, hyposmia and unilateral renal maldevelopment.

Measurements: LH and FSH were determined by RIA basally and after GnRH stimulation, and the test repeated after a period of GnRH priming. Testosterone response to hCG was measured. Arylsulphatase C assay was performed as a measure of steroid sulphatase activity. DNA amplification analysis and Southern blot analysis of four Xp22.3 loci were performed.

Results: Low levels of gonadotophins, basally and after acute GnRH, increased clearly after GnRH priming. Low testosterone levels increased promptly after hCG. Subnormal levels of arylsulphatase C were detected. Hyposmia and renal hypoplasia or aplasia were demonstrated. A large Xp 22.3 deletion including the genes responsible for X-linked ichthyosis (steroid sulphatase deficiency) and Kallmann syndrome was demonstrated.

Conclusions: The absence of the gene encoding steroid sulphatase accounts for the X-linked ichthyosis in these patients, whereas the absence of the Kallmann syndrome gene accounts for hypogonadism, anosmia and for the single kidney found in two of the three patients.