Genetic incidence of Kallmann syndrome & HH.

Kallmann syndrome and HH are genetic conditions. They are caused by a defect in a particular gene. Unlike some other genetic conditions there is no single gene defect that is responsible. At present there are 8 genes have been identified in having a role in causing KS or HH.

To complicate matters recent studies have suggested that unlike a lot of genetic conditions KS and HH are caused by two separate gene defects working in combination. This makes predicting the chances of passing on KS or HH through to the next generation very difficult.

The pie chart below shows the percentage incidence of genes involved with KS and HH. The most striking point is that 70% of KS and HH cases still have no genetic basis. This implies that there are still more genes to be discovered that can cause KS or HH or that the gene defects in some cases are so small they are not able to be identified by current techniques.

Incidence of IHH - Dr Nelly Pitteloud, Boston. 2008

At present the genes though to be responsible for KS and HH are:
FGFR1
NELF
KAL-1
PROK-2
PROKR-2
GNRHR
GPR-54

Each of these of these genes has a specific function. It is the loss of this function that causes the symptoms seen in KS and HH. Some of these genes are responsible for the development of the nasal system. If they fail to function it leads to the failure of the sense of smell seen in KS.

When the brain develops initially cells move about from the position they are created to the position they are supposed to be. This movement is over incredibly small distances but the failure to move can result in the failure in a certain part of the body not working correctly. Some of the genes mentioned above are responsible for this movement of cells.

One major cause of KS and HH is the failure of the movement of specialised cells into the hypothalamus. The absence of these cells means the hypothalamus is unable to produce a hormone known as GnRH (or LHRH) which is the major controlling hormone of puberty initiation and sexual development.