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Disease Profile

Fanconi anemia

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Childhood

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ICD-10

D61.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Fanconi pancytopenia; Fanconi's anemia

Categories

Blood Diseases; Congenital and Genetic Diseases; Kidney and Urinary Diseases;

Summary

Fanconi anemia (FA) affects the way genetic information (DNA) is copied and repaired. FA leads to bone marrow failure, skeletal abnormalities, and an increased risk for cancer. People with FA have a decreased number of red blood cells, white blood cells, and platelets leading to anemia, frequent infections, and excessive bleeding. In addition, people with FA may have limb, kidney, eye, skin, and genitourinary tract abnormalities. FA occurs due to variations in one of at least 22 genes. It is usually inherited in an autosomal recessive pattern, but it may also be inherited in an autosomal dominant or X-linked recessive pattern. FA can be diagnosed based on the symptoms, clinical exam, laboratory testing. The diagnosis may be confirmed by genetic testing. Treatment is focused on managing the symptoms. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for the blood problems associated with this condition.[1][2][3][4][5]

Symptoms

The following list includes the most common signs and symptoms in people with Fanconi anemia (FA). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms of Fanconi anemia may include:[1][2][4]

  • Shorter than average height
  • Abnormal patches of skin color
  • Abnormalities of the bones of the upper and lower limbs 
  • Small head size (microcephaly)
  • Eye abnormalities
  • Genitourinary tract malformation
  • Hearing loss
  • Structural heart defects
  • Hormone abnormalities

FA causes bone marrow failure that gets worse over time. This leads to low levels of red and white blood cells and platelets. Symptoms of bone marrow failure include anemia, infections, and excessive bleeding. As adults, people with FA have an increased risk of developing solid tumors and other specific types of cancer, especially myelodysplastic syndrome and acute myelogenous leukemia.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Cause

Most cases of Fanconi anemia occur when the FANCA, FANCC, or FANCG gene are not working correctly. In addition, there are at least nineteen other genes associated with Fanconi anemia. DNA changes known as pathogenic variants are responsible for making genes work incorrectly, or sometimes not at all.[1][2]

Diagnosis

Fanconi anemia is diagnosed based on the symptoms, clinical exam, and laboratory testing to look for signs of bone marrow failure, which may include low levels of red blood cells, white blood cells, and platelets. In addition, genetic testing can be used to confirm the diagnosis.[1][4]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment of Fanconi anemia is focused on managing the symptoms. Some people with FA benefit from a hematopoietic stem cell transplant, which is considered curative for the symptoms of bone marrow failure. Other treatments include medications to help manage kidney and hormone problems, as well as increased surveillance for cancer.[1][2][5]

    Specialists who may be involved in the care of someone with Fanconi anemia include:

    • Hematologist
    • Oncologist
    • Endocrinologist
    • Immunologist
    • Nephrologist
    • Orthopedist
    • Cardiologist
    • Ophthalmologist
    • Medical geneticist
    Medical Terms Other Names
    Learn More:
    HPO ID
    80%-99% of people have these symptoms
    Abnormality of chromosome stability
    0003220
    Aplasia/Hypoplasia of the radius
    0006501
    Hypopigmented skin patches
    Patchy loss of skin color
    0001053
    Irregular hyperpigmentation
    0007400
    Leukopenia
    Decreased blood leukocyte number
    Low white blood cell count

    [ more ]

    0001882
    Pyridoxine-responsive sideroblastic anemia
    0005522
    Short stature
    Decreased body height
    Small stature

    [ more ]

    0004322
    Thrombocytopenia
    Low platelet count
    0001873
    30%-79% of people have these symptoms
    Almond-shaped palpebral fissure
    Almond shaped eyes
    Almond-shaped opening between the eyelids

    [ more ]

    0007874
    Global developmental delay
    0001263
    Intellectual disability
    Mental deficiency
    Mental retardation
    Mental retardation, nonspecific
    Mental-retardation

    [ more ]

    0001249
    Microcephaly
    Abnormally small skull
    Decreased circumference of cranium
    Decreased size of skull
    Reduced head circumference
    Small head circumference

    [ more ]

    0000252
    Scoliosis
    0002650
    Short palpebral fissure
    Short opening between the eyelids
    0012745
    5%-29% of people have these symptoms
    Abnormal aortic morphology
    0001679
    Abnormal aortic valve morphology
    0001646
    Abnormal carotid artery morphology
    0005344
    Abnormal localization of kidney
    Abnormal localisation of kidneys
    0100542
    Abnormality of femur morphology
    Abnormality of the thighbone
    0002823
    Abnormality of the hypothalamus-pituitary axis
    0000864
    Abnormality of the liver
    Abnormal liver
    Liver abnormality

    [ more ]

    0001392
    Abnormality of the preputium
    0100587
    Absent testis
    Absent testes
    0010469
    Aganglionic megacolon
    Enlarged colon lacking nerve cells
    0002251
    Anal atresia
    Absent anus
    0002023
    Aplasia/Hypoplasia of fingers
    Absent/small fingers
    Absent/underdeveloped fingers

    [ more ]

    0006265
    Aplasia/Hypoplasia of the iris
    Absent/small iris
    Absent/underdeveloped iris

    [ more ]

    0008053
    Aplasia/Hypoplasia of the uvula
    0010293
    Arteriovenous malformation
    0100026
    Astigmatism
    Abnormal curving of the cornea or lens of the eye
    0000483
    Atrial septal defect
    An opening in the wall separating the top two chambers of the heart
    Hole in heart wall separating two upper heart chambers

    [ more ]

    0001631
    Azoospermia
    Absent sperm in semen
    0000027
    Bicornuate uterus
    Heart shaped uterus
    Heart-shaped uterus

    [ more ]

    0000813
    Cataract
    Clouding of the lens of the eye
    Cloudy lens

    [ more ]

    0000518
    Choanal atresia
    Blockage of the rear opening of the nasal cavity
    Obstruction of the rear opening of the nasal cavity

    [ more ]

    0000453
    Cleft palate
    Cleft roof of mouth
    0000175
    Clinodactyly of the 5th finger
    Permanent curving of the pinkie finger
    0004209
    Clubbing of toes
    0100760
    Cranial nerve paralysis
    0006824
    Cryptorchidism
    Undescended testes
    Undescended testis

    [ more ]

    0000028
    Decreased fertility in males
    0012041
    Dolichocephaly
    Long, narrow head
    Tall and narrow skull

    [ more ]

    0000268
    Duodenal stenosis
    0100867
    Epicanthus
    Eye folds
    Prominent eye folds

    [ more ]

    0000286
    External ear malformation
    0008572
    Facial asymmetry
    Asymmetry of face
    Crooked face
    Unsymmetrical face

    [ more ]

    0000324
    Finger syndactyly
    0006101
    Frontal bossing
    0002007
    Hearing impairment
    Deafness
    Hearing defect

    [ more ]

    0000365
    High palate
    Elevated palate
    Increased palatal height

    [ more ]

    0000218
    Hip dislocation
    Dislocated hips
    Dislocation of hip

    [ more ]

    0002827
    Hydrocephalus
    Too much cerebrospinal fluid in the brain
    0000238
    Hydroureter
    0000072
    Conditions with similar signs and symptoms from Orphanet
    FA clinical manifestations overlap with many malformation syndromes (Dubowitz, Seckel, Holt-Oram, Baller-Gerold, thrombocytopenia-absent radius, Nijmegen breakage syndromes, VACTERL association, dyskeratosis congenita; see these terms) and diagnosis of FA is often delayed until a patient develops BMF or malignancies. FA should be considered in the differential diagnosis of all young patients with BMF of unknown etiology. Other cancer predisposition syndromes (Bloom, Rothmund-Thomson or Werner syndromes; see these terms) or syndromes with pancytopenia (Diamond-Blackfan anemia, immune pancytopenia, Pearson or Shwachman-Diamond syndromes; see these terms) should be considered.
    Visit the Orphanet disease page for more information.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
      • Genetics Home Reference (GHR) contains information on Fanconi anemia. This website is maintained by the National Library of Medicine.
      • The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.
      • The National Heart, Lung, and Blood Institute (NHLBI) has information on this topic. NHLBI is part of the National Institutes of Health and supports research, training, and education for the prevention and treatment of heart, lung, and blood diseases.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Fanconi anemia. Click on the link to view a sample search on this topic.

          Selected Full-Text Journal Articles

            References

            1. Mehta PA, Tolar J. Fanconi anemia. GeneReviews®. Seattle (WA): University of Washington, Seattle. Updated Mar, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1401.
            2. Bhandari J, Thada PK, Puckett Y. Fanconi Anemia. In: StatPearls. Treasure Island (FL): StatPearls Publishing. Updated: June 21, 2020; https://www.ncbi.nlm.nih.gov/books/NBK559133.
            3. Taylor AMR, Rothblum-Oviatt C, Ellis NA, et al. Chromosome instability syndromes. Nat Rev Dis Primers. 2019; 5(1):64. https://pubmed.ncbi.nlm.nih.gov/31537806.
            4. Fiesco-Roa MO, Giri N, McReynolds LJ, Best AF, Alter BP. Genotype-phenotype associations in Fanconi anemia: A literature review. Blood Rev. 2019; 37:100589. https://pubmed.ncbi.nlm.nih.gov/31351673.
            5. Ebens CL, MacMillan ML, Wagner JE. Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations. Expert Rev Hematol. 2017; 10(1):81-97. https://pubmed.ncbi.nlm.nih.gov/27929686.

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