Kallmann syndrome is also called hypothalamic hypogonadism, familial hypogonadism with anosmia, and hypogonadotropic hypogonadism based on the mechanism.

Kallmann syndrome is a form of secondary hypogonadism, reflecting that the primary cause of the defect in sex-hormone production lies within the pituitary and hypothalamus rather than a physical defect of the testes or ovaries.

Signs and symptoms

• Reduced sense of smell/ absent sense of smell
• Progressive loss of vision and color blindness
• Optic atrophy and nerve deafness
• Cleft palate
• Mirror movement disorder
• Renal agenesis
• Delayed puberty in females (primary amenorrhea), lack of secondary sexual characteristics (breast development)
• Dyspareunia- pain at the time intercourse
• Delayed puberty in males –micropenis and cyrptorchidism
• Decreased libido and erectile dysfunction- Infertility
• Osteoporosis

Causes

• Kallmann syndrome can be inherited as an X-linked recessive trait, in which case there is a defect in the KAL1 gene, which maps to chromosome Xp22
• Mutations of the DAX1 gene lead to X-linked idiopathic hypogonadotropic hypogonadism.
• Loss-of-function mutations of the gene encoding FGFR1 have been described in autosomal dominant Kallmann syndrome.

Complications

• Male infertility
• Midline facial defect
• Amenorrhea
• Nystagmus
• Female infertility
• Holoprosencephaly
• Hypogonadotropic hypogonadism

Tests and diagnosis

• Serum electrolytes
• Serum or urine beta-human chorionic gonadotropin level
• Serum (total or free) testosterone, estradiol, FSH and LH
• Serum thyroid-stimulating hormone and serum free thyroxine
• Serum insulin-like growth factor I and serum insulin-like growth factor binding protein 3
• Semen analysis

Imaging studies

• MRI brain
• 2D- Echo
• Ultrasound – kidney
• DEXA scan

Treatment

Androgen replacement in males with Kallmann syndrome restores libido, erectile function, and well-being.

In addition, androgen replacement promotes the development of secondary sex characteristics (eg, facial, axillary, and pubic hair) and increases muscle strength.

Either parenteral or transdermal testosterone is the drug of choice for androgen replacement.

Estrogen replacement therapy (conjugated estrogens and estriol) in females with Kallmann syndrome promotes the development of secondary sex characteristics, including breast development and menstrual function, and it may prevent osteoporosis.

Oral contraceptives may be used as replacement therapy in young women.

Pulsatile administration of gonadotropin (GnRH) by subcutaneous or preferably intravenous infusion restores pituitary-gonadal axis function and fertility in the majority of people with Kallmann syndrome