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Fanconi anemia complementation group E(FANCE)

MedGen UID:
463628
Concept ID:
C3160739
Disease or Syndrome
Synonym: FANCE
 
Gene (location): FANCE (6p21.31)
 
Monarch Initiative: MONDO:0010953
OMIM®: 600901

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 descriptions

From OMIM
Fanconi anemia (FA) is characterized by bone marrow failure, developmental abnormalities, cancer predisposition, and cellular hypersensitivity to DNA cross-linking agents such as mitomycin C (summary by de Winter et al., 2000). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650.  http://www.omim.org/entry/600901
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.

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.

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).  https://medlineplus.gov/genetics/condition/fanconi-anemia

Clinical features

From HPO
Leukemia
MedGen UID:
9725
Concept ID:
C0023418
Neoplastic Process
A cancer of the blood and bone marrow characterized by an abnormal proliferation of leukocytes.
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Horseshoe kidney
MedGen UID:
65140
Concept ID:
C0221353
Congenital Abnormality
A connection of the right and left kidney by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline.
Ectopic kidney
MedGen UID:
68661
Concept ID:
C0238207
Congenital Abnormality
A developmental defect in which a kidney is located in an abnormal anatomic position.
Renal agenesis
MedGen UID:
154237
Concept ID:
C0542519
Congenital Abnormality
Agenesis, that is, failure of the kidney to develop during embryogenesis and development.
Duplicated collecting system
MedGen UID:
346936
Concept ID:
C1858565
Anatomical Abnormality
A duplication of the collecting system of the kidney, defined as a kidney with two (instead of, normally, one) pyelocaliceal systems. The pyelocaliceal system is comprised of the renal pelvis and calices. The duplicated renal collecting system can be associated with a single ureter or with double ureters. In the latter case, the two ureters empty separately into the bladder or fuse to form a single ureteral orifice.
Short thumb
MedGen UID:
98469
Concept ID:
C0431890
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the thumb.
Absent radius
MedGen UID:
235613
Concept ID:
C1405984
Congenital Abnormality
Missing radius bone associated with congenital failure of development.
Absent thumb
MedGen UID:
480441
Concept ID:
C3278811
Finding
Absent thumb, i.e., the absence of both phalanges of a thumb and the associated soft tissues.
Complete duplication of thumb phalanx
MedGen UID:
767638
Concept ID:
C3554724
Finding
A complete duplication affecting one or more of the phalanges of the thumb. As opposed to a partial duplication were there is still a variable degree of fusion between the duplicated bones, a complete duplication leads to two separate bones appearing side to side (radio-ulnar axis) as seen on x-rays. A duplication leading to an accessory bone appearing in the proximo-distal axis on x-rays, this is actually a different entity called a Pseudoepiphyses (see according terms) sometimes also referred to as Hyperphalangism.
Abnormal heart morphology
MedGen UID:
6748
Concept ID:
C0018798
Congenital Abnormality
Any structural anomaly of the heart.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Pancytopenia
MedGen UID:
18281
Concept ID:
C0030312
Disease or Syndrome
An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Reticulocytopenia
MedGen UID:
167812
Concept ID:
C0858867
Finding
A reduced number of reticulocytes in the peripheral blood.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Hyperpigmentation of the skin
MedGen UID:
57992
Concept ID:
C0162834
Pathologic Function
A darkening of the skin related to an increase in melanin production and deposition.
Cafe-au-lait spot
MedGen UID:
113157
Concept ID:
C0221263
Finding
Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Anemic pallor
MedGen UID:
871323
Concept ID:
C4025811
Sign or Symptom
A type of pallor that is secondary to the presence of anemia.
Hypergonadotropic hypogonadism
MedGen UID:
184926
Concept ID:
C0948896
Disease or Syndrome
Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Chromosomal breakage induced by crosslinking agents
MedGen UID:
867372
Concept ID:
C4021737
Finding
Increased amount of chromosomal breaks in cultured blood lymphocytes or other cells induced by treatment with DNA cross-linking agents such as diepoxybutane and mitomycin C.
Prolonged G2 phase of cell cycle
MedGen UID:
871165
Concept ID:
C4025639
Cell or Molecular Dysfunction
Deficient excision of UV-induced pyrimidine dimers in DNA
MedGen UID:
871166
Concept ID:
C4025640
Finding

Recent clinical studies

Etiology

Takahashi J, Masuda T, Kitagawa A, Tobo T, Nakano Y, Abe T, Ando Y, Kosai K, Kobayashi Y, Matsumoto Y, Yoshizumi T, Mori M, Mimori K
Oncology 2022;100(2):101-113. Epub 2021 Nov 1 doi: 10.1159/000520582. PMID: 34724663
van Twest S, Murphy VJ, Hodson C, Tan W, Swuec P, O'Rourke JJ, Heierhorst J, Crismani W, Deans AJ
Mol Cell 2017 Jan 19;65(2):247-259. Epub 2016 Dec 13 doi: 10.1016/j.molcel.2016.11.005. PMID: 27986371
Fu C, Begum K, Overbeek PA
PLoS One 2016;11(3):e0144285. Epub 2016 Mar 3 doi: 10.1371/journal.pone.0144285. PMID: 26939056Free PMC Article
Yamashita T, Nakahata T
Int J Hematol 2001 Jul;74(1):33-41. doi: 10.1007/BF02982547. PMID: 11530803
de Winter JP, Léveillé F, van Berkel CG, Rooimans MA, van Der Weel L, Steltenpool J, Demuth I, Morgan NV, Alon N, Bosnoyan-Collins L, Lightfoot J, Leegwater PA, Waisfisz Q, Komatsu K, Arwert F, Pronk JC, Mathew CG, Digweed M, Buchwald M, Joenje H
Am J Hum Genet 2000 Nov;67(5):1306-8. Epub 2000 Sep 19 doi: 10.1016/S0002-9297(07)62959-0. PMID: 11001585Free PMC Article

Diagnosis

Polito D, Cukras S, Wang X, Spence P, Moreau L, D'Andrea AD, Kee Y
J Biol Chem 2014 Mar 7;289(10):7003-7010. Epub 2014 Jan 22 doi: 10.1074/jbc.M113.533976. PMID: 24451376Free PMC Article
Gordon SM, Alon N, Buchwald M
J Biol Chem 2005 Oct 28;280(43):36118-25. Epub 2005 Aug 26 doi: 10.1074/jbc.M507758200. PMID: 16127171
Adachi D, Oda T, Yagasaki H, Nakasato K, Taniguchi T, D'Andrea AD, Asano S, Yamashita T
Hum Mol Genet 2002 Dec 1;11(25):3125-34. doi: 10.1093/hmg/11.25.3125. PMID: 12444097
Taniguchi T, D'Andrea AD
Blood 2002 Oct 1;100(7):2457-62. doi: 10.1182/blood-2002-03-0860. PMID: 12239156
Wegner RD, Henrichs I, Joenje H, Schroeder-Kurth T
Clin Genet 1996 Dec;50(6):479-82. doi: 10.1111/j.1399-0004.1996.tb02716.x. PMID: 9147877

Therapy

Lin B, Li H, Zhang T, Ye X, Yang H, Shen Y
Aging (Albany NY) 2021 Feb 11;13(4):5718-5747. doi: 10.18632/aging.202499. PMID: 33592580Free PMC Article
Yu J, Zhang J, Xing H, Sun Y, Yang Z, Yang T, Cai C, Zhao X, Yang L, Ding P
Int J Nanomedicine 2016;11:6651-6666. Epub 2016 Dec 8 doi: 10.2147/IJN.S115773. PMID: 27994462Free PMC Article
Fu C, Begum K, Overbeek PA
PLoS One 2016;11(3):e0144285. Epub 2016 Mar 3 doi: 10.1371/journal.pone.0144285. PMID: 26939056Free PMC Article
Gordon SM, Alon N, Buchwald M
J Biol Chem 2005 Oct 28;280(43):36118-25. Epub 2005 Aug 26 doi: 10.1074/jbc.M507758200. PMID: 16127171

Prognosis

Takahashi J, Masuda T, Kitagawa A, Tobo T, Nakano Y, Abe T, Ando Y, Kosai K, Kobayashi Y, Matsumoto Y, Yoshizumi T, Mori M, Mimori K
Oncology 2022;100(2):101-113. Epub 2021 Nov 1 doi: 10.1159/000520582. PMID: 34724663
Lin B, Li H, Zhang T, Ye X, Yang H, Shen Y
Aging (Albany NY) 2021 Feb 11;13(4):5718-5747. doi: 10.18632/aging.202499. PMID: 33592580Free PMC Article
Chandrasekharappa SC, Chinn SB, Donovan FX, Chowdhury NI, Kamat A, Adeyemo AA, Thomas JW, Vemulapalli M, Hussey CS, Reid HH, Mullikin JC, Wei Q, Sturgis EM
Cancer 2017 Oct 15;123(20):3943-3954. Epub 2017 Jul 5 doi: 10.1002/cncr.30802. PMID: 28678401Free PMC Article
Donahue SL, Lundberg R, Campbell C
J Mol Biol 2004 Oct 1;342(5):1443-55. doi: 10.1016/j.jmb.2004.08.013. PMID: 15364573
Wegner RD, Henrichs I, Joenje H, Schroeder-Kurth T
Clin Genet 1996 Dec;50(6):479-82. doi: 10.1111/j.1399-0004.1996.tb02716.x. PMID: 9147877

Clinical prediction guides

Takahashi J, Masuda T, Kitagawa A, Tobo T, Nakano Y, Abe T, Ando Y, Kosai K, Kobayashi Y, Matsumoto Y, Yoshizumi T, Mori M, Mimori K
Oncology 2022;100(2):101-113. Epub 2021 Nov 1 doi: 10.1159/000520582. PMID: 34724663
Lin B, Li H, Zhang T, Ye X, Yang H, Shen Y
Aging (Albany NY) 2021 Feb 11;13(4):5718-5747. doi: 10.18632/aging.202499. PMID: 33592580Free PMC Article
Zahnreich S, Weber B, Rösch G, Schindler D, Schmidberger H
DNA Repair (Amst) 2020 Dec;96:102992. Epub 2020 Oct 6 doi: 10.1016/j.dnarep.2020.102992. PMID: 33069004
Chandrasekharappa SC, Chinn SB, Donovan FX, Chowdhury NI, Kamat A, Adeyemo AA, Thomas JW, Vemulapalli M, Hussey CS, Reid HH, Mullikin JC, Wei Q, Sturgis EM
Cancer 2017 Oct 15;123(20):3943-3954. Epub 2017 Jul 5 doi: 10.1002/cncr.30802. PMID: 28678401Free PMC Article
Bouffard F, Plourde K, Bélanger S, Ouellette G, Labrie Y, Durocher F
J Mol Biol 2015 Sep 25;427(19):3056-73. Epub 2015 Aug 12 doi: 10.1016/j.jmb.2015.08.004. PMID: 26277624

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