Kallmann Syndrome

Kallmann syndrome (KS) is a congenital form of hypogonadotropic hypogonadism (HH) that manifests with hypo- or anosmia. This decrease in gonadal function is due to a failure in the differentiation or migration of neurons that arise embryologically in the olfactory mucosa to take up residence in the hypothalamus serving as gonadotropin-releasing hormone (GnRH) neurons. A deficit in the GnRH hormone results in decreased levels of sex steroids leading to a lack of sexual maturity and the absence of secondary sexual characteristics. Typical diagnosis occurs when a child fails to begin puberty. First described in 1944, the condition is a rare pediatric genetic disease estimated to affect 1 in 48,000 individuals. Treatment involves life-long hormone replacement therapy. However, treatment for male infants may include early hormone treatment or surgery to correct undescended testicles. Unfortunately, later in life, these patients have an increased risk of developing osteoporosis due to decreased sex hormones production and are often prescribed Vitamin D supplementation and bisphosphonates.

Like other HH conditions, Kallmann syndrome is characterized by reproductive features centered around a lack of sexual maturation during the years of puberty. These signs can include a lack of testicular development determined by testicular volume in men and a failure to start menstruation (amenorrhea) in women. Poorly defined secondary sexual characteristics can include a lack of pubic hair and underdeveloped mammary glands. Micropenis may also be present in a small portion of male cases, while cryptorchidism or undescended testicles may have been present at birth. These traits are related to low levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which consequentially results in low testosterone in males and estrogen and progesterone in women.

In addition to the reproductive deficits of HH conditions, there will also be other non-reproductive characteristics, which are often defects of embryological origin. KS is defined by its additional presentation of anosmia or hyposmia. Approximately 60% of patients with GnRH deficiency present with an impaired sense of smell and could be identified as having KS, cleft palate and lip, hypodontia, and cleft hand or foot are also frequently present along with unilateral renal agenesis. Cerebral impairments may also be present, including central hearing impairment, mirror movements of the hands (synkinesis), and ataxia. Color-blindness and ocular window defects have also been observed.