The biallelic Lynch syndrome is an inheritable disease caused by two mistakes in the hereditary material. As a result children and adults will have an increased chance to develop various forms of cancer.
The biallelic Lynch syndrome and its many names
- Constitutional MisMatch Repair Deficiency (CMMRD)
CMMRD arises when there are mutations on the MisMatch Repair (MMR) genes MLH1, MSH2, MSH6 en PMS2. In case of a mutation on one of these genes it would mean that the person would have Lynch syndrome. When it is a double mutation on one and the same MMR gene it is called CMMRD or rather the biallelic Lynch syndrome.
- Childhood cancer syndrome
Another name would be the childhood cancer syndrome, owing to the fact that the mistakes in the hereditary material cause assorted forms of cancer particularly in children.
How common is it for children?
It is not yet known how common the syndrome is for it is a relatively unknown disease. Therefore, more often than not, the diagnosis is not yet made for many children.
The biallelic Lynch syndrome is caused by two mistakes in the same place on the hereditary material. A child has two chromosomes of each, children who are diagnosed with the biallelic Lynch syndrome have got a ‘mistake’ on each chromosome on the exact same place. Numerous mistakes are found to cause the biallelic Lynch syndrome. These are on the PMS2-gene, MSH1-gene, MSH6-gene or the MLH1-gene. There might be more to it than this but as said before, this syndrome is rather unknown so research is still being conducted.
Mismatch repair genes
Most people have two working copies of each of the MMR genes in their cells. One copy is inherited from the mother and one from the father. A change in the gene that causes it to not work properly is called a mutation. When someone inherits an MMR gene mutation from the mother and another mutation in the same MMR gene from the father, they have constitutional mismatch repair deficiency syndrome. In other words, this person has a mutation affecting each of the 2 copies of an MMR gene. When a cell divides itself both cells should receive full genetic material of all chromosomes. That is why the DNA of the chromosomes is doubled before the cells divide. During this doubling of DNA mistakes are made. Normally these mistakes are restored by the mismatch repair system, whenever something is wrong with this system these mistakes are not repaired and a cancer cell may arise.
A large part of the children with the biallelic Lynch syndrome has multiple spots on the skin, these are referred to as cafe-au-lait spots. They are similar to the spots found when someone is diagnosed with neurofibramatosis type 1 although they are often less harshly restricted. Another thing that can appear is freckles in armpits and groins just as they are found in children with NF1.
Increased risk of cancer
For people with this syndrome the exact risk of developing cancer during their lifetime is not known at this time. It is expected to be very high in these people. Because constitutional mismatch repair deficiency syndrome can cause a wide variety of cancers, it is hard to predict what type of cancer a child with this condition may develop and when that cancer will occur. The increased risk of cancer expresses itself mostly in the form of braintumours, leukemia, lymphomas, stomach- and boweltumours and other Lynch related tumours. In addition to those there are also other types of tumours disclosed, for example the Wilms tumour. Due to the fact that the biallelic Lynch syndrome has only been recognized a few years ago, many others types of cancer may join the list.
When the biallelic Lynch syndrome becomes a possibility, the diagnosis can be established by means of a blood test.