Kallmann syndrome in women: from genes to diagnosis and treatment

Kallmann syndrome (KS) can be characterized as genetic disorder marked by hypogonadotropic hypogonadism and anosmia. Franz Jozef Kallmann was the first who described this disease in 1944. He suggested, that this disease has hereditary background. At present, six genes are regarded as causal genes of KS. These genes can be listed in chronological order: KAL1, FGFR1, FGF8, CHD7, PROKR2 and PROK2. The sensitivity of molecular testing of KS is only about 30%. Diagnosis based on clinical findings is therefore such important. Cardinal features of patients with KS include hypogonadotropic hypogonadism and anosmia or hyposmia. Some nonreproductive, non-olfactory symptoms can also be present, depending on the genetic form of disease. Some patients with KS present midline cranial anomalies (cleft lip, cleft palate and imperfect fusion). Sometimes patients can also suffer from missing teeth (dental agenesis). Optic problems, such as colour blindness or optic atrophy also can occur in KS patients. Very characteristic symptom in KS patients is mirror movements of the upper limbs (imitation synkinesis for contralateral limbs). The type of treatment in women with KS depends on the goal of therapy. After the diagnosis of syndrome, the main goal of the treatment is to induce and maintain secondary sex characteristic (estrogen-progestin therapy). The further goal in some patients can be related to enable fertility (gonadotropin, gonadotropin-releasing hormone therapy).