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Genetics of Kallmann syndrome / Congenital Hypogonadotropic Hypogonadism.

September 16, 2017

Mol Cell Endocrinol. Author manuscript; available in PMC 2012 Oct 22.

Published in final edited form as:
Mol Cell Endocrinol. 2011 Oct 22; 346(1-2): 102–109. Published online 2011 Jun 1. doi: 10.1016/j.mce.2011.05.041

Link to review paper on genetic testing in Kallmann syndrome / CHH. 


Two common questions that are asked by Kallmann syndrome or CHH patients are;

How did I inherit this condition ?


What are the chances of me passing on the condition to my offspring ?

Unlike some other genetic conditions unfortunately there is rarely an easy answer to either of these questions. This is mainly due to the fact that the genetic basis of Kallmann syndrome / CHH is still a mystery for the majority of cases.

The above diagram is taken from a review paper published in 2011. It lists eleven different genes which are known to be involved in cases of Kallmann syndrome / CHH. These are only the eleven best studied genes. The total number of genes that have been shown to have caused cases of Kallmann syndrome / CHH has now reached thirty.

Even if you took all these thirty genes, combined they would only account for about 50% of the cases of Kallmann syndrome / CHH, the rest have an unknown genetic, or idiopathic, cause.

The first discovered gene linked to Kallmann syndrome was the KAL-1 gene. This is the most widely studied gene and is fairly easy to test for. It causes a very specific form of Kallmann syndrome called x-linked Kallmann syndrome. This is the form that is inherited through the female line, with only males actually having the condition. As shown in the diagram above this gene only accounts for about 6% of Kallmann syndrome / CHH cases.

Genetic screening and testing can only test for a small number of these genes. In clinical testing normally only the 5 or 6 most common genes are screened for due to cost and time constraints. Even then this testing is only to see if a particular gene variant is there or not, it can not tell if there is a small error inside the gene. (An analogy would be that basic genetic testing can tell you if a particular book is in a library but it can not tell you if there are a couple of pages of information missing from that book).

Unless you know the exact gene or genes involved in an individual case of Kallmann syndrome it is very difficult to predict the outcome of a pregnancy. Normally genetic counsellors would need three generations of a family history to be able to identify the gene or genes involved and to give an idea of the chances of passing on the condition.

Without knowing the exact nature of the genetic origin of the disorder it is normally very difficult to tell how the condition was inherited, even if it was inherited.

Due to the nature of the genes already identified all the different forms of inheritance known are possible in Kallmann syndrome / CHH. The condition could have been pass down from either or both parents. It could also be caused by a new or novel mutation that occurred in the formation of the sperm or egg cells which therefore is not present in either parent.

National Institutes for Health guide on genetics.

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