What are the IBMFS disorders?
Fanconi Anemia (FA)
Fanconi Anemia patients have relatively specific physical findings in ~75% of affected persons. Laboratory
findings include aplastic
chromosome breakage in
cells grown in the presence of a chemical which damages DNA, mutation in one of the 15 separate genes
which have been identified ("cloned"), or assignment
to one of the sub-categories into which patients with
Fanconi Anemia can be classified (known as "complementation groups").
Bone marrow failure is NOT required for the diagnosis, and ~25%
of all persons eventually diagnosed as being affected by Fanconi Anemia do not
have the typical Fanconi Anemia findings on physical examination. Fanconi Anemia has been
diagnosed at ages ranging from birth to >50 years of age. Males
and females are affected equally.
- What are the major findings on physical examination?
- Café au lait spots (brown birth marks)
- Short stature
- Abnormal thumbs, often including abnormal radii (these are
the bones in the lower arm, between the elbow and the wrist)
- Abnormal male development, infertility
- Small head
- Small eyes
- Abnormal kidneys
- What is the age at diagnosis?
- Anytime from birth to 50 years of age
- Usually by age 10 to 15 years
- What is the pattern of bone marrow failure?
- Often called aplastic anemia, which is diagnosed when all 3 types of cells
(red cells, white cells and platelets)
are abnormally low because the bone marrow is not producing them.
- Low red cell count ("anemia",
often with large red cells)
- Low platelet count (platelets are the cells in the blood which help the blood to clot)
- Low white cell count (white cells help the body fight off infection)
- What specific kinds of cancer
(cancer of the blood and bone marrow)
- Liver tumors
- Solid organ cancer
- Cancers of the mouth, tongue and throat ("head and neck")
- Cancers of the female genitals, particularly labial and cervical cancer ("gynecologic")
- Cancer of the esophagus ("gastrointestinal")
- Brain tumors
- Possibly others
- How is Fanconi Anemia specifically diagnosed?
- The chromosome breakage test
- The patientís blood cells are treated in the laboratory with a chemical which damages
(the basic chemical for all genes).
- The breaks are large enough to be seen under a microscope, and are counted.
- Mutation analysis (genetic testing)
- Laboratories can now identify the specific genetic "error"
(or mutation) in some patients, in genes called FANCX, where X
stands for the Fanconi Anemia complementation group A through N.
- There are at least 15 different gene pairs (complementation groups) responsible for Fanconi Anemia: FANCA, FANCB, FANCC, FANCD1 (BRCA2), FANCD2, FANCE, FANCF, FANCG(XRCC9), FANCI (KIAAA1794), FANCJ (BACH1/BRIP1), FANCL (PHF9/POG), FANCM (Hef), FANCN (PALB2), FANCO (RAD51C), and FANCP (SLX4). About 5-10% of patients do not have mutations in these genes, and more genes need to be discovered.
- The disease is primarily inherited
in an autosomal recessive
manner (FANCB is X-linked, requiring inheritance of a mutant
gene from the mother only). This means that illness occurs
only if a person has two abnormal (mutant) genes from the
same complementation group. One abnormal gene is inherited from each parent. Persons like the parents, who
have only one copy of the abnormal gene, are called "gene carriers."