Genetic Diagnosis of Hypogonadotropic Hypogonadism and Kallmann Syndrome

This chapter discusses the genetic diagnosis of idiopathic hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KSS). Idiopathic hypogonadotropic hypogonadism is clinically manifested as absent or impaired pubertal development due to low sex steroid levels and low serum gonadotropin levels. The association of IHH with anosmia or hyposmia is known as Kallmann syndrome. The chapter evaluates delayed puberty, the diagnosis of IHH and KS, as well as the molecular basis of genes that causes these disorders. Delayed puberty is characterized by absence of development of breast by age 13 or menses by age 15 in girls and in boys, absence of signs of puberty. The diagnosis of delayed puberty is done by testing thyroid function, serum prolactin and thyroxine. Chromosomal abnormalities and single gene mutations occurs in IHH and KS and the genes involved in these disorders are presented. In male patients, genetic testing of KAL1 gene mutations for classic Kallman syndrome should be considered and these mutations result in X-linked recessive diseases. In about 10% of IHH patients, mutations in the FGFR1 gene have been reported and it was the first gene recognized to cause normosmic IHH and KS.