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Fanconi anemia, complementation group M

MedGen UID:
854019
Concept ID:
C3469529
Disease or Syndrome

Disease characteristics

Excerpted from the GeneReview: Fanconi Anemia
Fanconi anemia (FA) is characterized by physical abnormalities, bone marrow failure, and increased risk for malignancy. Physical abnormalities, present in approximately 75% of affected individuals, include one or more of the following: short stature, abnormal skin pigmentation, skeletal malformations of the upper and/or lower limbs, microcephaly, and ophthalmic and genitourinary tract anomalies. Progressive bone marrow failure with pancytopenia typically presents in the first decade, often initially with thrombocytopenia or leukopenia. The incidence of acute myeloid leukemia is 13% by age 50 years. Solid tumors – particularly of the head and neck, skin, and genitourinary tract – are more common in individuals with FA. [from GeneReviews]
Authors:
Parinda A Mehta  |  Christen Ebens   view full author information

Additional description

From MedlinePlus Genetics
Fanconi anemia is a condition that affects many parts of the body. People with this condition may have bone marrow failure, physical abnormalities, organ defects, and an increased risk of certain cancers.

The major function of bone marrow is to produce new blood cells. These include red blood cells, which carry oxygen to the body's tissues; white blood cells, which fight infections; and platelets, which are necessary for normal blood clotting. Approximately 90 percent of people with Fanconi anemia have impaired bone marrow function that leads to a decrease in the production of all blood cells (aplastic anemia). Affected individuals experience extreme tiredness (fatigue) due to low numbers of red blood cells (anemia), frequent infections due to low numbers of white blood cells (neutropenia), and clotting problems due to low numbers of platelets (thrombocytopenia). People with Fanconi anemia may also develop myelodysplastic syndrome, a condition in which immature blood cells fail to develop normally.

More than half of people with Fanconi anemia have physical abnormalities. These abnormalities can involve irregular skin coloring such as unusually light-colored skin (hypopigmentation) or café-au-lait spots, which are flat patches on the skin that are darker than the surrounding area. Other possible symptoms of Fanconi anemia include malformed thumbs or forearms and other skeletal problems including short stature; malformed or absent kidneys and other defects of the urinary tract; gastrointestinal abnormalities; heart defects; eye abnormalities such as small or abnormally shaped eyes; and malformed ears and hearing loss. People with this condition may have abnormal genitalia or malformations of the reproductive system. As a result, most affected males and about half of affected females cannot have biological children (are infertile). Additional signs and symptoms can include abnormalities of the brain and spinal cord (central nervous system), including increased fluid in the center of the brain (hydrocephalus) or an unusually small head size (microcephaly).

Individuals with Fanconi anemia have an increased risk of developing a cancer of blood-forming cells in the bone marrow called acute myeloid leukemia (AML) or tumors of the head, neck, skin, gastrointestinal system, or genital tract. The likelihood of developing one of these cancers in people with Fanconi anemia is between 10 and 30 percent.  https://medlineplus.gov/genetics/condition/fanconi-anemia

Recent clinical studies

Etiology

Wu X, Krishna Sudhakar H, Alcock LJ, Lau YH
J Med Chem 2023 Aug 24;66(16):11271-11281. Epub 2023 Aug 9 doi: 10.1021/acs.jmedchem.3c00674. PMID: 37555818
Morales-Pison S, Morales-González S, Fernandez-Ramires R, Tapia JC, Maldonado E, Calaf GM, Jara L
Int J Mol Sci 2023 Feb 17;24(4) doi: 10.3390/ijms24044041. PMID: 36835452Free PMC Article
Zhang X, Zhang S, Liu Z, Zhao W, Zhang X, Song J, Jia H, Yang W, Ma Y, Wang Y, Xie K, Budahn H, Wang H
Nucleic Acids Res 2023 Jan 11;51(1):198-217. doi: 10.1093/nar/gkac1209. PMID: 36583364Free PMC Article
Dzaparidze G, Kazachonok D, Gvozdkov A, Taelma H, Laht K, Minajeva A
Pathol Res Pract 2021 Jun;222:153436. Epub 2021 Apr 8 doi: 10.1016/j.prp.2021.153436. PMID: 33857855
Kasak L, Punab M, Nagirnaja L, Grigorova M, Minajeva A, Lopes AM, Punab AM, Aston KI, Carvalho F, Laasik E, Smith LB; GEMINI Consortium, Conrad DF, Laan M
Am J Hum Genet 2018 Aug 2;103(2):200-212. doi: 10.1016/j.ajhg.2018.07.005. PMID: 30075111Free PMC Article

Diagnosis

Rashid MU, Muhammad N, Shehzad U, Khan FA, Loya A, Hamann U
Fam Cancer 2023 Jan;22(1):31-41. Epub 2022 Jul 8 doi: 10.1007/s10689-022-00304-1. PMID: 35802266
Dzaparidze G, Kazachonok D, Gvozdkov A, Taelma H, Laht K, Minajeva A
Pathol Res Pract 2021 Jun;222:153436. Epub 2021 Apr 8 doi: 10.1016/j.prp.2021.153436. PMID: 33857855
Kasak L, Punab M, Nagirnaja L, Grigorova M, Minajeva A, Lopes AM, Punab AM, Aston KI, Carvalho F, Laasik E, Smith LB; GEMINI Consortium, Conrad DF, Laan M
Am J Hum Genet 2018 Aug 2;103(2):200-212. doi: 10.1016/j.ajhg.2018.07.005. PMID: 30075111Free PMC Article
Knoll A, Higgins JD, Seeliger K, Reha SJ, Dangel NJ, Bauknecht M, Schröpfer S, Franklin FC, Puchta H
Plant Cell 2012 Apr;24(4):1448-64. Epub 2012 Apr 30 doi: 10.1105/tpc.112.096644. PMID: 22547783Free PMC Article
Singh TR, Bakker ST, Agarwal S, Jansen M, Grassman E, Godthelp BC, Ali AM, Du CH, Rooimans MA, Fan Q, Wahengbam K, Steltenpool J, Andreassen PR, Williams DA, Joenje H, de Winter JP, Meetei AR
Blood 2009 Jul 2;114(1):174-80. Epub 2009 May 7 doi: 10.1182/blood-2009-02-207811. PMID: 19423727Free PMC Article

Prognosis

Rashid MU, Muhammad N, Shehzad U, Khan FA, Loya A, Hamann U
Fam Cancer 2023 Jan;22(1):31-41. Epub 2022 Jul 8 doi: 10.1007/s10689-022-00304-1. PMID: 35802266
Dzaparidze G, Kazachonok D, Gvozdkov A, Taelma H, Laht K, Minajeva A
Pathol Res Pract 2021 Jun;222:153436. Epub 2021 Apr 8 doi: 10.1016/j.prp.2021.153436. PMID: 33857855
Wang Y, Wang J, Long F, Wang N, Zhang B, Han H, Wang Y
Breast Cancer 2018 Jul;25(4):431-437. Epub 2018 Jan 31 doi: 10.1007/s12282-018-0841-0. PMID: 29388117

Clinical prediction guides

Wu X, Krishna Sudhakar H, Alcock LJ, Lau YH
J Med Chem 2023 Aug 24;66(16):11271-11281. Epub 2023 Aug 9 doi: 10.1021/acs.jmedchem.3c00674. PMID: 37555818
Rashid MU, Muhammad N, Shehzad U, Khan FA, Loya A, Hamann U
Fam Cancer 2023 Jan;22(1):31-41. Epub 2022 Jul 8 doi: 10.1007/s10689-022-00304-1. PMID: 35802266
Dzaparidze G, Kazachonok D, Gvozdkov A, Taelma H, Laht K, Minajeva A
Pathol Res Pract 2021 Jun;222:153436. Epub 2021 Apr 8 doi: 10.1016/j.prp.2021.153436. PMID: 33857855

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    Curated

    • FARF, 2020
      Fanconi Anemia Clinical Care Guidelines, Fifth Edition.
    • FARF, 2008
      Fanconi Anemia Research Fund, Guidelines for Diagnosis and Management, 2008 (See 2020 Update)

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