Fanconi Anaemia

What is Fanconi Anaemia?
Fanconi Anaemia is group of rare genetic disorders characterised by bone marrow failure, resulting in the bone marrow being unable to produce an adequate amount of blood cells. It is a multi-system disease that can impact different parts of the body.

What causes Fanconi Anaemia?
Fanconi Anaemia occurs due to variants (changes) in genes that play a role in repairing damaged DNA. Due to these changes, cells are unable to fix DNA properly, leading to chromosomal instability. Although 23 genes have been linked with Fanconi Anaemia, majority of individuals have variants in 3 genes (FANCA, FANCC and FANCG) which play a role in generating the ‘FA core’ protein complex.

How is Fanconi Anaemia passed on?
Fanconi Anaemia generally has an autosomal recessive inheritance pattern, meaning that 2 changed copies, one from each parent, are present in an affected individual. However, some changes can be inherited through different patterns, such as X-linked in FANCB and autosomal dominant in FANCR/RAD51.

What are the symptoms of Fanconi Anaemia?
The symptoms of Fanconi Anaemia may present at any age, but most individuals with Fanconi Anaemia have symptoms either at birth or in childhood. They may include:
• Short stature
• Skeletal changes: hip or limb abnormalities such as club feet
• Bone marrow failure: easy bruising, lethargy, frequent infections
• Increased risk of certain cancers such as head and neck cancers, acute myeloid leukaemia
• Café-au-lait spots (light to dark pigmented spots on the skin)
• Micro-orchidism
• Heart abnormalities
• Kidney abnormalities
It is important to recognise that since Fanconi Anaemia can impact different body parts, the symptoms and severity of these symptoms can vary.

How do we diagnose Fanconi Anaemia?
Individuals suspected of having Fanconi Anaemia undergo a thorough diagnostic process involving a range of healthcare workers which may include doctors and genetic counsellors. This process may include blood and genetic tests.

How do we manage Fanconi Anaemia?
Fanconi Anaemia is a complex condition to which there is no cure currently. With the help of a multi-disciplinary team, the unique needs of individuals are addressed. This may include genetic counselling, blood transfusions and cancer monitoring. The service in Manchester is headed by Dr Stefan Meyer at the Royal Manchester Children’s Hospital. In some individuals, with FANC-A FA, gene therapy could be offered as part of several clinical trials.

Credits:

Sharan Reghunathan – University of Mancheser 5th year medical student

 

Sources