Inheritance of
Kallmann's and Hypogonadotrophic Hypogonadism.
This page will give a brief overview of the possibilites on inheriting Kallmann's syndrome or HH.
For a more detailed description of the current thinking on the genetics of Kallmann's or HH, click here Current views on the genetics of Kallmanns.
One very important consideration when starting fertility treatment is the question of inheritance of Kallmann's or Hypogonadotrophic Hypogonadism (HH).
Both Kallmann's syndrome and other forms of HH can be
passed down successive generations.
In the absence of any firm information to the contrary
it should be assumed that any case of Kallmann's or HH could be passed on to
future generations if a person undergoes fertility treatment.
The chance of this occurring is not easy to answer. It will depend on the type of Kallmann's or HH a person has. Very few people will know what type of Kallmann's they have. Unless you come from a family with an established history of Kallmann's or HH it would be very difficult for a doctor to tell you for certain what type of Kallmann's you have.
Even if you are the only person in your family with Kallmann's there is still a chance of passing it on to your children.
The percentage chances of passing it on will range from 0% to 50% in the worst-case scenario.
To give some examples:
The two most widely studied genes involved in causing Kallmann's and HH are KAL-1 and KAL-2.
KAL-1 is on the x-chromosome
KAL-2 is on chromosome 8, so it follows slightly
different rules than KAL-1.
KAL-1
KAL-1 is the most widely studied gene, a defect in this gene will cause classic x-linked Kallmann's syndrome. This is most widely studied gene that caused Kallmann's and HH, but it probably not the most common cause.
A normal mum will be XX
A normal dad will be XY
A mum who carries the defective KAL-1 gene, but not have Kallmann's will be XX
A dad who has Kallmann's caused by the KAL-1 gene will be XY.
Case 1.
Mum who carries the defective KAL-1 gene + normal dad
XX + XY = 4 possibilities XX XY XX XY
XX 25% chance of having a girl who carries the defective gene
XY 25% chance of having a boy with x-linked Kallmann's
XX 25% chance of having a normal girl
XY 25% chance of having a normal boy
It would be very unlikely that the mum would know she carried the defective KAL-1 gene. This is the usual case that occurs when a 'sporadic' or isolated case of Kallmann's occurs within a family.
Case 2.
Normal mum + dad with x-linked Kallmann's caused by defective KAL-1
XX + XY = 4 possibilities XX XY XX XY
XX 50% chance of having a girl who carries the defective gene
XY 50% chance of having a normal boy
Case 3. (very unlikely situation)
Mum who carries the gene + dad with x-linked Kallmann's
XX + XY =4 possibilities XX XY XX XY
XX 25% chance of having a girl with x-linked Kallmann's. This situation has never been reported as actually occurring.
XY 25% chance of having a boy with x-linked Kallmann's
XX 25% chance of having a normal girl
XY 25% chance of having a normal boy
KAL-2
The KAL-2 gene follows different rules in its inheritance. It is carried on chromosome 8, so it is called an autosomal gene. Its rules of inheritance are a lot simpler than for an x-linked gene.
It is a 'dominant' gene defect and any defect will override a normal copy of the gene.
Case 1.
Mum with Kallmann's caused by a defective KAL-2 gene + normal dad
Case 2.
Normal mum + dad with Kallmann's caused by a defective KAL-2 gene.
In both cases the outcomes are the same. There is a 50% chance of passing the defective gene to an offspring. Conversely there is a 50% chance of passing on the normal copy of the gene.
In both cases:
25% chance of having a normal boy
25% chance of having a normal girl
25% chance of having a girl with Kallmann's or HH caused by defective KAL-2 gene
25% chance of having a boy with Kallmann's or HH caused by defective KAL-2 gene
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In theory it is possible to screen a person for these particular genes. However this is not normally practical.
It is very expensive to do this type of screening, especially if the defect in the gene is very small, and is very time consuming to undertake.
These 2 genes, KAL-1 and KAL-2 represent only the current initial understanding genetic inheritance of Kallmann's or HH and only cover about 50% of all Kallmann's and HH cases. The rest of the cases still have an unknown genetic origin.