Abstract
Many of the recent advances in our understanding of human reproductive biology and its genetic basis have arisen directly via the genetic investigation of patients with Kallmann syndrome and their families. The disease is characterised by the association of an isolated defect in the secretion (or, less commonly, action) of gonadotropin-releasing hormone (GnRH) and consequent infertility, with anosmia and potentially other associated non-reproductive features. GnRH-producing neurons are located in the hypothalamic brain region after a peculiar migration during embryonic life. To date, different genes affecting GnRH neuron development/migration have so far been implicated in Kallmann syndrome, but our knowledge of the genetic basis of the syndrome remains incomplete. From a clinical point of view, the disease has suffered from a lack of definitive diagnosis and treatment, and although progress has been made in terms of timely diagnosis and evidence-based treatment of patients, implementation remains inconsistent. These aspects will be discussed in this review, which examines new strategies for arriving at more evidence-based and patient-centred medical practice in Kallmann syndrome.