Fanconi Anaemia

Fanconi Anaemia

What is Fanconi Anaemia?
This is a rare, inherited (genetic) disease with a wide range of symptoms including severe anaemia, immune system failure, malformations and defects of the thumb and the bones in the arms (radius), darkening of the skin (hyperpigmentation), growth retardation and kidney abnormalities. In addition, the chromosomes (DNA) of a person with Fanconi Anaemia have an increased sensitivity to mitogenic (chromosome breaking ) agents and this may causes a high susceptibility to aplastic anaemia, acute myeloblastic leukaemia or squamous cell carcinoma. Diagnosis usually occurs in children between the ages of 3 and 12 years thus, monitoring all symptoms early could prevent the disease from developing serious consequences.

Who is likely to get Fanconi Anaemia?
Genetic diseases are often more common in specific community groups. Fanconi Anaemia however, is not restricted to any particular ethnic or regional group. 1 person in 500 in the general population may be a carrier (heterogeneous) of the faulty gene (mutation) and is likely to be unaffected by the disorder. Approximately 2 persons in one million will inherit a 'double dose' (homozygous) of the faulty gene and will develop a severe form of the fatal disease. Within particular community groups it is becoming possible to test for the presence of some of the faulty genes, for example 1 in 100 Ashkenazi Jews is known to be a carrier of the specific mutation IVS4+4(A-->T) in the FA-C group.

What causes the disease?
Fanconi Anaemia is a result of an inborn error and is caused by inheriting a 'double dose' of a fault in the FA gene. The FA genes are found on chromosomes number 9 and/or 20 and mutations on these genes to date have been found to have 8 different groups (complementations) named from FA-A to FA-H. Fanconi Renal Syndrome and Anaemia may also be acquired in association with other medical problems.

How is the disease transmitted?
Fanconi anaemia is transmitted by autosomal recessive mode i.e. when two unaffected carriers of the FA gene mutation become parents, then for each pregnancy: fan

There is a 1-in-4 (25%) chance that the child will inherit the normal gene from both parents and will be completely free of the gene mutation and will not be affected by Fanconi Anaemia (Figure A).
There is a 2-in-4 (50%) chance that the child will inherit both a regular copy and a faulty copy of the FA gene and will be a carrier of the faulty gene, unaffected by the disease, just like his/her parents (Figures B and C).
There is a 1-in-4 (25%) chance that the child will inherit the faulty gene from both parents. This child will be affected by Fanconi Anaemia (figure D).

Does it affect One's health to be a carrier of the FA gene mutation?
Carriers of the gene mutation are usually unaffected by Fanconi Anaemia.

Does Fanconi Anaemia only affect males?
NO. This disease can affect both males and females.

Is it possible to test if a preson is a carrier of a faulty gene?
YES. Molecular genetic studies will identify the FA gene mutation. To date however, only the IVS 4+4(A->T) mutation is identified by our laboratory. This mutation accounts for the majority of Fanconi Anaemia in Ashkenazi Jews and is not usually found in other community groups.

For whom is genetic carrier testing relevant?
Anyone with a family history of the disease should be tested. It is relevant for Ashkenazi Jews to be tested because the faulty FA gene may be silently passed through generations.

How is the test performed?
Blood samples are collected for Chromosomal and DNA testing. DNA testing will identify the FA gene mutation. During pregnancy (pre-natal) the amniotic fluid may also be tested.

Can Fanconi Anaemia disease be cured?
It is hoped that in the near future gene therapy will be used to cure the disease . Currently , bone marrow transplant is available for Fanconi Anaemia patients with life threatening symptoms such as aplastic anaemia and acute leukaemia .

Is genetic carrier testing available for other conditions?
YES. After discussing family history and ethnic background, our laboratory can test for genetic carrier status of some other inherited disorders at the same time as testing for Fanconi Anaemia .

Contact: PaLMS Laboratory & Community Genetics: Ph:992-68899 Fax:9926-8484 Email:aproos@doh.health.nsw.gov.au