SNP Shot: Genomic Insights

Kallmann syndrome is a medical condition defined by the absence or delay of puberty combined with a reduced or absent sense of smell.

This condition falls under the category of hypogonadotropic hypogonadism. This type of hypogonadism arises from insufficient production of hormones crucial for guiding sexual development. These hormones are normally produced in the hypothalamus, a region of the brain. Males with hypogonadotropic hypogonadism may exhibit an unusually small penis (micropenis) and undescended testicles (cryptorchidism). During puberty, most individuals affected by this disorder fail to develop typical secondary sex characteristics. For males, this includes the lack of facial hair growth and voice deepening. For females, this includes the absence of menstruation and breast development. Both sexes typically experience a diminished or absent growth spurt. If left untreated, the majority of men and women with Kallmann syndrome are unable to conceive children biologically (infertility).

A hallmark of Kallmann syndrome is a diminished (hyposmia) or complete lack (anosmia) of the sense of smell. This distinguishes it from most other forms of hypogonadotropic hypogonadism, which do not affect the ability to smell. Many individuals with Kallmann syndrome are unaware of their olfactory impairment until it is discovered through specific testing.

Kallmann syndrome can manifest with a variety of additional signs and symptoms. These may include the absence of one kidney at birth (unilateral renal agenesis), bone abnormalities in the fingers or toes, a cleft lip (with or without a cleft palate), abnormal eye movements, hearing loss, and dental abnormalities. Some individuals may exhibit bimanual synkinesis, a condition where the movements of one hand are mirrored by the other. This can impair the ability to perform tasks requiring independent hand movements, such as playing musical instruments.

Inheritance:

When Kallmann syndrome is linked to mutations in the ANOS1 gene, it follows an X-linked recessive inheritance pattern. The ANOS1 gene resides on the X chromosome, one of the two sex chromosomes. In males (who possess a single X chromosome), a single altered copy of the gene is sufficient to cause the condition. In females (who have two X chromosomes), both copies of the gene must carry the mutation for the disorder to develop. Notably, there are no documented cases of females with two ANOS1 gene mutations. A defining characteristic of X-linked inheritance is that fathers cannot transmit X-linked traits to their sons. In most instances, individuals with Kallmann syndrome due to an ANOS1 gene mutation inherit the mutation from their mothers, who carry one altered copy of the gene in each cell (and typically show no symptoms of the condition). In other cases, the syndrome arises from a new ANOS1 gene mutation.

When Kallmann syndrome stems from mutations in other genes, it frequently exhibits an autosomal dominant inheritance pattern. This signifies that a single altered copy of the gene in each cell is enough to cause the disorder. An affected individual may inherit the mutation from a parent with the condition. Alternatively, the condition can result from a new gene mutation in an individual with no family history of the disorder.

In some families, Kallmann syndrome has demonstrated an autosomal recessive inheritance pattern. This means that both copies of the gene in each cell must carry mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they usually do not exhibit any signs or symptoms of the condition.