Fanconi anemia (FA) is a rare inherited disorder that impairs the body’s ability to repair damaged DNA, leading to bone marrow failure, physical abnormalities, and a dramatically elevated cancer risk. Only about 50% of people with FA are expected to live to age 33, though survival has improved significantly with advances in transplant medicine and early screening.
FA affects roughly 1 in every 130,000 births. It is not the same as Fanconi syndrome, a kidney disorder with a similar name but an entirely different cause.
How FA Disrupts DNA Repair
Your cells constantly encounter DNA damage, including a particularly dangerous type called interstrand crosslinks, where the two strands of the DNA double helix become fused together. Healthy cells fix this damage using a repair system known as the FA pathway (sometimes called the FA-BRCA pathway). In this system, a group of eight proteins assembles into a complex that flags the damage site, tagging a pair of repair proteins so they can travel to the broken DNA and coordinate the fix. Specialized cutting enzymes then snip away the damaged section, and the cell rebuilds it using a healthy copy of the gene as a template.
In Fanconi anemia, mutations in the genes that produce these repair proteins cause the entire system to malfunction. Damaged DNA accumulates, chromosomes become unstable, and cells either die prematurely or begin growing abnormally. This genomic instability is the root cause of nearly every complication FA produces, from failing bone marrow to cancer.
Genetics and Inheritance
Mutations in more than 20 different genes can cause FA. However, 80 to 90 percent of cases trace back to just three of them: FANCA, FANCC, and FANCG. The condition is almost always inherited in an autosomal recessive pattern, meaning a child must receive a faulty copy of the same gene from both parents to develop the disease. Parents who each carry one mutated copy typically have no symptoms themselves.
Where the mutation falls within these genes can influence what the disease looks like. Variants in the genes that operate earlier in the repair pathway tend to produce a milder physical presentation. Certain mutations in FANCA, particularly in a specific region of the gene, are linked to higher rates of head and neck cancers and gynecological cancers later in life.
Physical Signs at Birth
About 75% of children born with FA have visible physical abnormalities, though the specific features vary widely. Common signs include abnormal or missing thumbs, underdeveloped forearm bones, short stature, patches of abnormal skin pigmentation (including café-au-lait spots), and a smaller-than-average head. Kidney malformations, hearing problems, and eye abnormalities also occur.
Roughly 5% of FA patients have a cluster of birth defects affecting the spine, heart, kidneys, and limbs that overlaps with a pattern called VACTERL association. The remaining 25% of patients look physically normal at birth, which can delay diagnosis until blood problems appear years later.
Bone Marrow Failure
The hallmark complication of FA is progressive bone marrow failure. Because the marrow’s blood-forming stem cells are especially sensitive to DNA damage, they gradually die off. This leads to dropping blood counts across all cell types: red blood cells (causing fatigue and pallor), white blood cells (increasing infection risk), and platelets (causing easy bruising and bleeding).
Most children with FA develop noticeably low blood counts during childhood, often between ages 5 and 10, though the timing varies. As the marrow continues to fail, some patients progress to myelodysplastic syndrome, a precancerous condition where the marrow produces abnormal, poorly functioning blood cells. From there, the risk of developing acute myeloid leukemia rises substantially.
Cancer Risk
FA patients face a cancer risk that dwarfs the general population’s. Overall, their observed cancer rate is roughly 50 times higher than expected. For blood cancers, the risk is up to 800 times greater. For solid tumors, particularly squamous cell carcinomas of the head, neck, and genital tract, the risk is 500 to 700 times higher than normal.
These squamous cell cancers tend to appear at unusually young ages, sometimes in the teens or twenties, and can be aggressive. The mouth, throat, and esophagus are the most common sites. For women with FA, the cervix and vulva are also high-risk areas. This elevated cancer risk persists even after successful bone marrow transplantation, which is why lifelong surveillance is essential.
How FA Is Diagnosed
The gold-standard diagnostic test for FA is the chromosome breakage test. A blood sample is drawn, and the cells are exposed to a DNA-damaging chemical called diepoxybutane (DEB). In healthy cells, the repair machinery fixes the damage efficiently. In FA cells, chromosomes shatter and fuse into abnormal shapes called radial figures. If 30% or more of the treated cells show these radial formations, the test is considered positive.
An alternative chemical, mitomycin C, can also be used, but it carries a higher chance of false-positive results. The DEB test is highly reliable, though false negatives can occasionally occur when a patient’s blood cells have undergone a phenomenon called somatic reversion, where some cells spontaneously correct the mutation on their own. In equivocal cases, testing skin cells instead of blood can help clarify the diagnosis. Genetic testing then identifies the specific gene mutation involved.
Treatment: Stem Cell Transplant
The only cure for the bone marrow failure component of FA is a stem cell transplant (also called a bone marrow transplant). This procedure replaces the patient’s defective marrow with healthy donor cells. A matched sibling donor produces the best outcomes, but unrelated donor transplants have improved significantly over the past two decades.
FA patients are unusually sensitive to the chemotherapy and radiation typically used to prepare the body for a transplant, so doctors use much gentler conditioning regimens. Among patients who survive at least two years after transplant, the long-term outlook is encouraging: 10-year survival is around 90%, and 15-year survival is approximately 79%. Of 157 patients tracked in one long-term study, 12 of 20 late deaths occurred more than five years after the transplant, often from cancers rather than transplant-related complications.
Transplant restores healthy blood production but does not eliminate the underlying DNA repair defect in other tissues, which is why the elevated solid tumor risk remains.
Lifelong Cancer Screening
Because of the persistent cancer threat, FA patients follow an intensive surveillance schedule for life. Current guidelines recommend dental and oral screenings every six months, starting in childhood, to catch early signs of mouth and throat cancers. Annual skin exams monitor for skin cancers. For women, annual gynecological exams begin at age 18 or when they become sexually active, whichever comes first.
These screenings are especially important after a stem cell transplant, since the transplant process itself can increase the risk of secondary cancers in the mouth and skin. Early detection makes a meaningful difference in outcomes, as squamous cell cancers in FA patients can progress quickly.
Living With FA
Beyond blood counts and cancer risk, FA affects daily life in ways that vary from person to person. Short stature is common, and some patients have hormonal deficiencies that affect growth, puberty, or fertility. Hearing loss may require aids or intervention. Learning differences occur in some children, though many have normal cognitive development.
For patients who have not yet developed severe marrow failure, treatment focuses on supportive care: blood transfusions when counts drop, growth hormone if needed, and close monitoring. Androgens, a class of hormones, can temporarily boost blood counts in some patients, buying time before a transplant becomes necessary. The goal is to maintain quality of life while watching carefully for the complications that require more aggressive intervention.