[Genetic anomalies of the gonadotropic axis]

Some forms of isolated hypogonadotropic hypogonadism are caused by mutations of the GnRH receptor gene. These mutations lead to inactivation of the receptor and are recessive. A unique disease that associates hypogonadotropic hypogonadism and congenital hyperplasia is caused by mutations in the DAX-1 gene, situated on chromosome X. The pathogenesis to these endocrine defects remains now elusive. Kallmann syndrome represents the association of hypogonadotropic hypogonadism due to GnRH deficiency, and anosmia. Additional developmental anomalies can be present. Three modes of inheritance have been described: X-linked, autosomal recessive and autosomal dominant. The X-linked KAL-1 gene has been cloned. It encodes an extracellular matrix protein, anosmin-1, the study of which should lead to a better understanding of this developmental disease.