15th April 2024

Kallman syndrome

Background

Kallman syndrome is a congenital hypogonadotropic hypogonadism associated with hypo/anosmia (1). It occurs due to a failure of gonadotrophin releasing neurons to migrate from the olfactory placode to the hypothalamus (2, 3). It is a relatively rare condition thought to affect 1 out of 48,000 people (1).

Aetiology

Kallman syndrome is a clinically and genetically heterogenous condition with ~60% of cases occurring due to sporadic mutations (1), inherited Kallman syndrome has different patterns of inheritance (Autosomal recessive, Autosomal dominant and X-chromosome recessive(1)). There are several different genes associated with Kallman syndrome, with the most common mutations occurring in the ANOS1 and FGFR1 genes (4)

Presentation

Patients with Kallman syndrome will present with symptoms of hypogonadism and pubertal failure in association with hyposmia/anosmia. It may also be associated with other phenotypical features such as cleft lip/palate, poor hearing, dental agenesis, renal agenesis and limb anomalies (1).

References

• Laitinen EM, Vaaralahti K, Tommiska J, Eklund E, Tervaniemi M, Valanne L, et al. Incidence, phenotypic features and molecular genetics of Kallmann syndrome in Finland. Orphanet J Rare Dis. 2011;6:41.
• Schwanzel-Fukuda M, Bick D, Pfaff DW. Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome. Brain Res Mol Brain Res. 1989;6(4):311-26.
• Cariboni A, Maggi R. Kallmann’s syndrome, a neuronal migration defect. Cell Mol Life Sci. 2006;63(21):2512-26.
• Cangiano B, Swee DS, Quinton R, Bonomi M. Genetics of congenital hypogonadotropic hypogonadism: peculiarities and phenotype of an oligogenic disease. Hum Genet. 2021;140(1):77-111.