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Fanconi anemia complementation group I(FANCI)

MedGen UID:
323016
Concept ID:
C1836861
Disease or Syndrome
Synonym: FANCI
 
Gene (location): FANCI (15q26.1)
 
Monarch Initiative: MONDO:0012186
OMIM®: 609053

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 a clinically and genetically heterogeneous disorder that causes genomic instability. Characteristic clinical features include developmental abnormalities in major organ systems, early-onset bone marrow failure, and a high predisposition to cancer. The cellular hallmark of FA is hypersensitivity to DNA crosslinking agents and high frequency of chromosomal aberrations pointing to a defect in DNA repair (summary by Deakyne and Mazin, 2011). For additional general information and a discussion of genetic heterogeneity of Fanconi anemia, see 227650.  http://www.omim.org/entry/609053
From MedlinePlus Genetics
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.

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).

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.

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

Clinical features

From HPO
Vesicoureteral reflux
MedGen UID:
21852
Concept ID:
C0042580
Disease or Syndrome
Vesicoureteral reflux (VUR) is characterized by the reflux of urine from the bladder into the ureters and sometimes into the kidneys. It is a risk factor for urinary tract infections. Primary VUR results from a developmental defect of the ureterovesical junction (UVJ). In combination with intrarenal reflux, the resulting inflammatory reaction may result in renal injury or scarring, also called reflux nephropathy (RN). Extensive renal scarring impairs renal function and may predispose patients to hypertension, proteinuria, and renal insufficiency (summary by Lu et al., 2007). Genetic Heterogeneity of Vesicoureteral Reflux A locus designated VUR1 maps to chromosome 1p13. VUR2 (610878) is caused by mutation in the ROBO2 gene (602431) on chromosome 3p12; VUR3 (613674) is caused by mutation in the SOX17 gene (610928) on chromosome 8q11; VUR4 (614317) maps to chromosome 5; VUR5 (614318) maps to chromosome 13; VUR6 (614319) maps to chromosome 18; VUR7 (615390) maps to chromosome 12; and VUR8 (615963) is caused by mutation in the TNXB gene (600985) on chromosome 6p21. A possible X-linked form has been reported (VURX; 314550).
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.
Renal hypoplasia
MedGen UID:
120571
Concept ID:
C0266295
Congenital Abnormality
Hypoplasia of the kidney.
Abnormal renal morphology
MedGen UID:
1633142
Concept ID:
C4551596
Anatomical Abnormality
Any structural anomaly of the kidney.
Short thumb
MedGen UID:
98469
Concept ID:
C0431890
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the thumb.
Hypoplasia of the radius
MedGen UID:
672334
Concept ID:
C0685381
Congenital Abnormality
Underdevelopment of the radius.
Absent radius
MedGen UID:
235613
Concept ID:
C1405984
Congenital Abnormality
Missing radius bone associated with congenital failure of development.
Short 1st metacarpal
MedGen UID:
376561
Concept ID:
C1849311
Finding
A developmental defect characterized by reduced length of the first metacarpal (long bone) of the hand.
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.
Patent ductus arteriosus
MedGen UID:
4415
Concept ID:
C0013274
Congenital Abnormality
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Patent foramen ovale
MedGen UID:
8891
Concept ID:
C0016522
Congenital Abnormality
Failure of the foramen ovale to seal postnatally, leaving a potential conduit between the left and right cardiac atria.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Abnormal cardiovascular system morphology
MedGen UID:
892473
Concept ID:
C4049796
Anatomical Abnormality
Any structural anomaly of the heart and blood vessels.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for 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).
Decreased body weight
MedGen UID:
1806755
Concept ID:
C5574742
Finding
Abnormally low body weight.
Duodenal atresia
MedGen UID:
75602
Concept ID:
C0266174
Congenital Abnormality
A developmental defect resulting in complete obliteration of the duodenal lumen, that is, an abnormal closure of the duodenum.
Conductive hearing impairment
MedGen UID:
9163
Concept ID:
C0018777
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
Atresia of the external auditory canal
MedGen UID:
78613
Concept ID:
C0266597
Congenital Abnormality
Absence or failure to form of the external auditory canal.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Chiari malformation
MedGen UID:
2065
Concept ID:
C0003803
Congenital Abnormality
Chiari malformation consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of CSF outflow.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Absent septum pellucidum
MedGen UID:
96561
Concept ID:
C0431371
Congenital Abnormality
Absence of the septum pellucidum (meaning translucent wall in Latin - SP), also known as the ventricle of Sylvius. The septum pellucidum is a thin, triangular double membrane separating the frontal horns of the right and left lateral ventricles of the brain. It extends between the anterior portion of the corpus callosum, and the body of the fornix and its width varies from 1.5 to 3.0 mm.
Colpocephaly
MedGen UID:
98131
Concept ID:
C0431384
Congenital Abnormality
Colpocephaly is an anatomic finding in the brain manifested by occipital horns that are disproportionately enlarged in comparison with other parts of the lateral ventricles.
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.
Small pituitary gland
MedGen UID:
868479
Concept ID:
C4022873
Anatomical Abnormality
An abnormally decreased size of the pituitary gland.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Bone marrow hypocellularity
MedGen UID:
383749
Concept ID:
C1855710
Finding
A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.
Fused cervical vertebrae
MedGen UID:
854386
Concept ID:
C3887527
Congenital Abnormality
A congenital anomaly characterized by a joining (fusion) of two or more cervical vertebral bodies with one another.
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.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
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.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Reduced circulating growth hormone concentration
MedGen UID:
1815075
Concept ID:
C5706169
Finding
Concentration of growth hormone in the blood circulation below normal limits.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
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.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Optic nerve hypoplasia
MedGen UID:
137901
Concept ID:
C0338502
Disease or Syndrome
Underdevelopment of the optic nerve.
Optic disc pallor
MedGen UID:
108218
Concept ID:
C0554970
Finding
A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression.
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.

Recent clinical studies

Etiology

Zhang S, Liu Y, Sun Y, Liu Q, Gu Y, Huang Y, Zeng Z, Tang F, Ouyang Y
Mol Cancer 2024 Jan 10;23(1):11. doi: 10.1186/s12943-023-01924-6. PMID: 38200551Free PMC Article
Olazabal-Herrero A, He B, Kwon Y, Gupta AK, Dutta A, Huang Y, Boddu P, Liang Z, Liang F, Teng Y, Lan L, Chen X, Pei H, Pillai MM, Sung P, Kupfer GM
Cell Rep 2024 Jan 23;43(1):113610. Epub 2024 Jan 1 doi: 10.1016/j.celrep.2023.113610. PMID: 38165804Free PMC Article
Cai Z, Duan Y, Li W, Liu Z, Gong Z, Hong S, He X, Xuanyuan X, Chen Y, Bi X, Wang W
Front Immunol 2023;14:1295831. Epub 2023 Nov 22 doi: 10.3389/fimmu.2023.1295831. PMID: 38077326Free PMC Article
Lim SW, Na D, Lee H, Fang X, Cui S, Shin YJ, Lee KI, Lee JY, Yang CW, Chung BH
Cells 2023 Sep 20;12(18) doi: 10.3390/cells12182319. PMID: 37759541Free PMC Article
Lemonidis K, Arkinson C, Rennie ML, Walden H
FEBS J 2022 Aug;289(16):4811-4829. Epub 2021 Jun 29 doi: 10.1111/febs.16077. PMID: 34137174

Diagnosis

Li Y, Zhang Y, Yang Q, Zhou X, Guo Y, Ding F, Liu Z, Luo A
Curr Cancer Drug Targets 2022;22(7):591-602. doi: 10.2174/1568009622666220331091709. PMID: 35362384
Birkbak NJ, Li Y, Pathania S, Greene-Colozzi A, Dreze M, Bowman-Colin C, Sztupinszki Z, Krzystanek M, Diossy M, Tung N, Ryan PD, Garber JE, Silver DP, Iglehart JD, Wang ZC, Szuts D, Szallasi Z, Richardson AL
Ann Oncol 2018 Apr 1;29(4):903-909. doi: 10.1093/annonc/mdy049. PMID: 29452344Free PMC Article

Therapy

Li Y, Zhang Y, Yang Q, Zhou X, Guo Y, Ding F, Liu Z, Luo A
Curr Cancer Drug Targets 2022;22(7):591-602. doi: 10.2174/1568009622666220331091709. PMID: 35362384
Birkbak NJ, Li Y, Pathania S, Greene-Colozzi A, Dreze M, Bowman-Colin C, Sztupinszki Z, Krzystanek M, Diossy M, Tung N, Ryan PD, Garber JE, Silver DP, Iglehart JD, Wang ZC, Szuts D, Szallasi Z, Richardson AL
Ann Oncol 2018 Apr 1;29(4):903-909. doi: 10.1093/annonc/mdy049. PMID: 29452344Free PMC Article

Prognosis

Zhang S, Liu Y, Sun Y, Liu Q, Gu Y, Huang Y, Zeng Z, Tang F, Ouyang Y
Mol Cancer 2024 Jan 10;23(1):11. doi: 10.1186/s12943-023-01924-6. PMID: 38200551Free PMC Article
Cai Z, Duan Y, Li W, Liu Z, Gong Z, Hong S, He X, Xuanyuan X, Chen Y, Bi X, Wang W
Front Immunol 2023;14:1295831. Epub 2023 Nov 22 doi: 10.3389/fimmu.2023.1295831. PMID: 38077326Free PMC Article
Hou Y, Li J, Yu A, Deng K, Chen J, Wang Z, Huang L, Ma S, Dai X
Int J Med Sci 2023;20(7):918-932. Epub 2023 May 12 doi: 10.7150/ijms.83760. PMID: 37324186Free PMC Article
Zhang J, Wang J, Wu J, Huang J, Lin Z, Lin X
Oncol Rep 2022 Aug;48(2) Epub 2022 Jun 15 doi: 10.3892/or.2022.8350. PMID: 35703356Free PMC Article
Birkbak NJ, Li Y, Pathania S, Greene-Colozzi A, Dreze M, Bowman-Colin C, Sztupinszki Z, Krzystanek M, Diossy M, Tung N, Ryan PD, Garber JE, Silver DP, Iglehart JD, Wang ZC, Szuts D, Szallasi Z, Richardson AL
Ann Oncol 2018 Apr 1;29(4):903-909. doi: 10.1093/annonc/mdy049. PMID: 29452344Free PMC Article

Clinical prediction guides

Zhang S, Liu Y, Sun Y, Liu Q, Gu Y, Huang Y, Zeng Z, Tang F, Ouyang Y
Mol Cancer 2024 Jan 10;23(1):11. doi: 10.1186/s12943-023-01924-6. PMID: 38200551Free PMC Article
Cai Z, Duan Y, Li W, Liu Z, Gong Z, Hong S, He X, Xuanyuan X, Chen Y, Bi X, Wang W
Front Immunol 2023;14:1295831. Epub 2023 Nov 22 doi: 10.3389/fimmu.2023.1295831. PMID: 38077326Free PMC Article
Lim SW, Na D, Lee H, Fang X, Cui S, Shin YJ, Lee KI, Lee JY, Yang CW, Chung BH
Cells 2023 Sep 20;12(18) doi: 10.3390/cells12182319. PMID: 37759541Free PMC Article
Sijacki T, Alcón P, Chen ZA, McLaughlin SH, Shakeel S, Rappsilber J, Passmore LA
Nat Struct Mol Biol 2022 Sep;29(9):881-890. Epub 2022 Sep 1 doi: 10.1038/s41594-022-00820-9. PMID: 36050501Free PMC Article
Zhang J, Wang J, Wu J, Huang J, Lin Z, Lin X
Oncol Rep 2022 Aug;48(2) Epub 2022 Jun 15 doi: 10.3892/or.2022.8350. PMID: 35703356Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • FARF, 2020
      Fanconi Anemia Clinical Care Guidelines, Fifth Edition.

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