Fanconi anemia overview: Difference between revisions
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== Pathophysiology == | == Pathophysiology == | ||
In order to understand the pathophysiology, it is important to understand normal physiology of DNA repair. There are eight ''FANC'' family members that are activated during times of DNA damage. These proteins function in repairing damaged genetic material. In patients with Fanconi anemia, there is impaired DNA damage response due to mutations in the ''FANC'' family genes, and this leads to chromosomal instability and susceptibility to cross-linking agents. These cross-linking agents can lead to the generation of reactive oxygen species. | In order to understand the pathophysiology, it is important to understand normal physiology of DNA repair. There are eight ''FANC'' family members that are activated during times of DNA damage. These proteins function in repairing damaged genetic material. In patients with Fanconi anemia, there is impaired DNA damage response due to mutations in the ''FANC'' family genes, and this leads to chromosomal instability and susceptibility to cross-linking agents. These cross-linking agents can lead to the generation of reactive oxygen species. | ||
== Causes == | |||
Fanconi anemia an [[autosomal recessive]] genetic disorder that is caused by mutations in various genes of the ''FANC'' family. | |||
== Differentiating Fanconi's Anemia From Other Diseases == | == Differentiating Fanconi's Anemia From Other Diseases == | ||
Revision as of 16:44, 4 May 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shyam Patel [2]
Overview
Fanconi anemia (FA) is a genetic disease that affects children and adults from all ethnic backgrounds.[1] The disease is named after the Swiss pediatrician who originally described this disorder, Guido Fanconi. FA is characterized by short stature, skeletal anomalies, increased incidence of solid tumors and leukemias, bone marrow failure (aplastic anemia), and cellular sensitivity to DNA damaging agents such as mitomycin C.
Historical perspective
The discovery of Fanconi anemia is largely the work of the Swiss pediatrician Guido Fanconi who observed various findings of the disease to be different than pernicious anemia. Over the coming decades, multiple advances in diagnostics have been made by various groups. Bone marrow transplant was optimized for Fanconi anemia in the 1980s. Most recently, in the 2010s, various new genomic alterations have been associated with Fanconi anemia.
Classification
Fanconi anemia is currently classified by complementation group.
Pathophysiology
In order to understand the pathophysiology, it is important to understand normal physiology of DNA repair. There are eight FANC family members that are activated during times of DNA damage. These proteins function in repairing damaged genetic material. In patients with Fanconi anemia, there is impaired DNA damage response due to mutations in the FANC family genes, and this leads to chromosomal instability and susceptibility to cross-linking agents. These cross-linking agents can lead to the generation of reactive oxygen species.
Causes
Fanconi anemia an autosomal recessive genetic disorder that is caused by mutations in various genes of the FANC family.
Differentiating Fanconi's Anemia From Other Diseases
Fanconi Anemia must be differentiated from Aplastic Anemia, Paraoxysomal Nocturnal Hemoglobinuria, and Chromosomal breakage syndrome and Hereditary Bone marrow failure syndrome (Dyskeratosis congenita and other short telomere syndromes).
- Fanconi Anemia must be differentiated from other diseases that cause Pancytopenia, Congenital anomalies, and associated with malignancy such as Aplastic Anemia, Rare chromosomal breakage syndrome and inherited bone marrow failure.[2]
- As Fanconi Anemia resembles with variety of other diseases that causes pancytopenia.
- Must be differentiated on basis on congenital anomalies and chromosomal breakage test.[3]
Epidemiology and Demographics
FA is rare overall, but it is one of the most common inherited bone marrow failure syndromes.
- The incidence of FA is approximately 1 in 100,000 to 250,000 births.
- Approximately 10 to 20 children are born with FA each year in the United States.[4]
- The probability of FA in the US population, FA, was estimated to be 1 in 129,600 births
- Most children are diagnosed between six and nine years of age, concurrent with the onset of bone marrow failure . Rarely, marrow failure from FA can present in infants and small children
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
History and Symptoms
Physical Examination
- Congenital malformations are the most common presenting features of FA.
- Patients with FA usually present with hypo/hyperpigmentation, café-au-lait spots, short staure and thumb or other radial abnormalities.
- Vital Signs Usually normal sometime patients present with fever due to superimposed infection.
- Skin abnormalities in Fanconi anemia can include generalized hyperpigmentation on the trunk, neck, and intertriginous areas, the aforementioned café au lait spots, and hypopigmented areas. Delicate features can also be characteristic of patients.
Laboratory Findings
Electrocardiogram
X-ray
CT
MRI
Ultrasound
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
References
- ↑ Krausz C, Riera-Escamilla A, Chianese C, Moreno-Mendoza D, Ars E, Rajmil O; et al. (2018). "From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia". Genet Med. doi:10.1038/s41436-018-0037-1. PMID 29904161.
- ↑ Hartung HD, Olson TS, Bessler M (2013). "Acquired aplastic anemia in children". Pediatr Clin North Am. 60 (6): 1311–36. doi:10.1016/j.pcl.2013.08.011. PMC 3894991. PMID 24237973.
- ↑ Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM; et al. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–405. doi:10.1182/blood-2016-03-643544. PMID 27069254.
- ↑ Rochowski A, Rosenberg PS, Alonzo TA, Gerbing RB, Lange BJ, Alter BP (2012). "Estimation of the prevalence of Fanconi anemia among patients with de novo acute myelogenous leukemia who have poor recovery from chemotherapy". Leuk Res. 36 (1): 29–31. doi:10.1016/j.leukres.2011.09.009. PMC 4008327. PMID 21974856.