Kallmann Syndrome (KS) is a rare genetic disorder that belongs to the spectrum of isolated hypogonadotropic hypogonadism. This decrease in gonadal function is due to a failure in differentiation or migration of neurons that embryologically arise in the olfactory mucosa and travel to the hypothalamus. Thus, a particular feature of Kallman Syndrome is the presence of either anosmia (lack of sense of smell) or severe hyposmia. Some non-reproductive, non-olfactory symptoms can also be present, depending on the genetic form of disease which include cranial anomalies, missing teeth, optic problems and/or congenital heart disease. Inability to attain puberty or failure to fully complete it is one of the main forms of presentation and an early interventional replacement therapy could prevent further complications derived from a delay in treatment. It is inherited typically in an autosomal dominant fashion.
The Igenomix Kallmann Syndrome Precision Panel can be used to make a directed and accurate diagnosis as well as a differential diagnosis of hypogonadotropic hypogonadism ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
The clinical utility of this panel is:
GENE | OMIM DISEASES | INHERITANCE* | % GENE COVERAGE (20X) | HGMD** |
ANOS1 | Hypogonadotropic | X,XR,G | 96.86 | – |
CCDC141 | Hypogonadotropic | AR | 99.7 | 1 of 1 |
CHD7 | Charge Syndrome, | AD | 96.25 | 823 of 896 |
DCC | Familial Horizontal | AD,AR | 94 | 39 of 39 |
DUSP6 | Hypogonadotropic | AD,AR | 99.36 | 4 of 4 |
FEZF1 | Hypogonadotropic | AR | 99.95 | 3 of 3 |
FGF17 | Hypogonadotropic | AD,AR | 99.98 | 8 of 8 |
FGF8 | Hypogonadotropic | AD | 98.36 | 38 of 38 |
FGFR1 | Encephalocraniocutaneous | AD | 100 | 279 of 280 |
FLRT3 | Hypogonadotropic Hypogonadism | AD | 99.98 | 7 of 7 |
GNRH1 | Hypogonadotropic Hypogonadism | AR | 100 | 12 of 12 |
GNRHR | Hypogonadotropic Hypogonadism | AR | 100 | 59 of 59 |
HESX1 | Septooptic Dysplasia, | AD,AR | 100 | 26 of 26 |
HS6ST1 | Hypogonadotropic | AD | 99.97 | 8 of 8 |
IL17RD | Hypogonadotropic | AD,AR | 99.95 | 17 of 17 |
KISS1 | Hypogonadotropic | AR | 100 | 9 of 10 |
KISS1R | Hypogonadotropic | AD,AR | 99.41 | 42 of 43 |
NDNF | Hypogonadotropic | AD | 99.33 | – |
NSMF | Hypogonadotropic | AD | 99.69 | 11 of 11 |
PROK2 | Hypogonadotropic | AD | 100 | 20 of 20 |
PROKR2 | Hypogonadotropic | AD | 100 | 64 of 64 |
SEMA3A | Hypogonadotropic | AD | 100 | 29 of 29 |
SOX10 | Peripheral Demyelinating | AD | 99.74 | 139 of 147 |
SPRY4 | Hypogonadotropic | AD,AR | 99.72 | 13 of 13 |
TAC3 | Hypogonadotropic | AR | 100 | 10 of 10 |
TACR3 | Hypogonadotropic | AR | 99.97 | 40 of 40 |
WDR11 | Hypogonadotropic | AD,AR | 100 | 19 of 19 |
* Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial
** HGMD: Number of clinically relevant mutations according to HGMD
Stamou, M. I., & Georgopoulos, N. A. (2018). Kallmann syndrome: phenotype and genotype of hypogonadotropic hypogonadism. Metabolism: clinical and experimental, 86, 124–134. https://doi.org/10.1016/j.metabol.2017.10.012
Meczekalski, B., Podfigurna-Stopa, A., Smolarczyk, R., Katulski, K., & Genazzani, A. R. (2013). Kallmann syndrome in women: from genes to diagnosis and treatment. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology, 29(4), 296–300. https://doi.org/10.3109/09513590.2012.752459
Bonomi, M., Libri, D., Guizzardi, F., Guarducci, E., Maiolo, E., & Pignatti, E. et al. (2011). New understandings of the genetic basis of isolated idiopathic central hypogonadism. Asian Journal Of Andrology, 14(1), 49-56. doi: 10.1038/aja.2011.68
Dodé, C., Teixeira, L., Levilliers, J., Fouveaut, C., Bouchard, P., Kottler, M. L., Lespinasse, J., Lienhardt-Roussie, A., Mathieu, M., Moerman, A., Morgan, G., Murat, A., Toublanc, J. E., Wolczynski, S., Delpech, M., Petit, C., Young, J., & Hardelin, J. P. (2006). Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS genetics, 2(10), e175. https://doi.org/10.1371/journal.pgen.0020175
Pingault, V., Bodereau, V., Baral, V., Marcos, S., Watanabe, Y., & Chaoui, A. et al. (2013). Loss-of-Function Mutations in SOX10 Cause Kallmann Syndrome with Deafness. The American Journal Of Human Genetics, 92(5), 707-724. doi: 10.1016/j.ajhg.2013.03.024
Sonne, J., & Lopez-Ojeda, W. (2020). Kallmann Syndrome. In StatPearls. StatPearls Publishing.
