Neue Erkenntnisse zur Genetik des Kallmann-Syndroms und des Idiopathischen Hypogonadotropen Hypogonadismus (IHH)*

Abstract

Kallmann syndrome (KS) is characterised by hypogonadotropic hypogonadism due to GnRH deficiency and concomitant anosmia. The latter is absent in idiopathic hypogonadotropic hypogonadism (IHH), an entity otherwise indistinguishable from KS. Most patients with KS or IHH have no positive family history. Some of the familial cases of KS follow an X-linked recessive pattern of inheritance. This subtype is caused by deletions or point mutations in the KAL-1 gene. Its protein product, anosmin-1, is believed to play an important role in the morphogenesis of the peripheral olfactory system. Recent studies have shown that only a minority of patients with Kallmann syndrome carry mutations in the KAL-1 gene. Kallmann syndrome as well as IHH may also follow an autosomal dominant or autosomal recessive pattern of inheritance. With regard to the latter case, a single family has been described with mutations in the GnRH receptor gene. Other genes causing the autosomal subforms of KS/IHH remain to be identified. In sibships with multiple affected members marked clinical variability has been observed. Within a single family patients with either Kallmann syndrome, IHH, isolated anosmia, or only delayed or incomplete pubertal development may be seen. This hints at a close nosological relationship between these clinical phenotypes which may share a common - so far however rarely identifiable - genetic basis.