Kallmann Syndrome Info

Genetics

  • Kallmann syndrome is characterized by the association of congenital hypogonadotropic hypogonadism with anosmia (HHA)
  • Kallmann syndrome 1 (KS1), caused by mutations in KAL1, is inherited in an X-linked manner
  • KS2 (caused by mutations in FGFR1), KS3 (caused by mutations in PROKR2), and KS4 (caused by mutations in PROK2) are inherited in an autosomal dominant manner
  • KAL1, FGFR1, PROKR2, and PROK2 are the only genes known to be associated with Kallmann syndrome (KS).  Together, mutations in these genes account for about 20%-25% of KS.

Incidence
Estimates of the overall incidence of KS vary from approximately 1:10,000 to 1:86,000

Major Phenotypic Features

  • Hypogonadotropic hypogonadism
  • Low or normal serum concentration of LH (luteinizing hormone) and FSH (follicle stimulating hormone) in the setting of low circulating concentrations of sex steroids [total testosterone (T) <100 ng/dL in males and estradiol (E2) <50 pg/mL in females]
  • Congenital anosmia (complete inability to smell) or hyposmia (decreased ability to smell)
  • Absence of secondary sexual features
  • It can occasionally be associated with;
    • Optic problems, such as color blindness or optic atrophy
    • Nerve deafness
    • Cleft palate
    • Cryptorchidism
    • Renal agenesis
    • Bimanual synkinesia

Clinical Management
Treatment is directed at restoring the deficient hormones.  Males are administered human chorionic gonadotropin (hCG) or testosterone.  Females are treated with estrogen and progestins.