The Importance of Autosomal Genes in Kallmann Syndrome: Genotype-Phenotype Correlations and

Kallmann syndrome (KS) consists of congenital, isolated, idio-pathic hypogonadotropic hypogonadism (IHH) and anosmia. The gene responsible for the X-linked form of KS, KAL, encodes a protein, anosmin, that plays a key role in the migration of GnRH neurons and olfactory nerves to the hypothalamus. In addition to X-linked pedi-grees, autosomal dominant and recessive kindreds with KS have been reported. The relative importance of these autosomal vs. X-linked genes in producing KS, and the frequency of KAL mutations, are currently unknown because these are rare disorders and large series are unusual. We examined 101 individuals with IHH (6 anosmia) and their families to determine their modes of inheritance, incidence of muta-tions in the coding sequence of KAL, genotype-phenotype correlations, and [in a subset (n 5 38)] their neuroendocrine phenotype