Etiology and Epidemiology
primarily inherited in an autosomal recessive manner .
At presentation, patients with FA may have:
(1) typical physical anomalies and abnormal hematologic findings (majority of the patients)
(2) normal physical features but abnormal hematologic findings (about one-third of patients)
(3) physical anomalies and normal hematologic findings (unknown percentage). 
Approximately 75% of patients are 3-14 yr of age at the time of diagnosis . 
Clinical Manifestations
The most common anomaly in FA is hyperpigmentation of the trunk, neck, and intertriginous areas, as well as café-au-lait spots and vitiligo, alone or incombination .
Half the patients have short stature. In some patients, growth failure is aggravated by abnormal growth hormone secretion or with hypothyroidism.
Absence of radii and thumbs that are hypoplastic, supernumerary, bifid, or absent are common.
Anomalies of the feet, congenital hip dislocation, and leg abnormalities are seen.
male patient with FA may have an underdeveloped penis; undescended, atrophic, or absence of the testes; and hypospadias or phimosis.
Females can have malformations of the vagina, uterus, and ovary.
Many patients have “facies,” including microcephaly, small eyes, epicanthal folds, and abnormal shape, size, or positioning of the ears .
Ectopic, pelvic, or horseshoe kidneys are detected by imaging and may show other organs as duplicated, hypoplastic, dysplastic, or absent kidneys.
CVS and GIT malformations also occur. Approximately 10% of patients with FA are cognitively delayed.
Laboratory Findings
Marrow failure usually ensues in the 1st decade of life. Thrombocytopenia and red blood cell macrocytosis often appears initially, with subsequent onset of granulocytopenia and then anemia.
Severe aplasia develops in most cases, but its full expression is variable and evolves over a period of months to years.
The marrow becomes progressively hypocellular and fatty, like that in severe acquired aplastic anemia.
Chromosome fragility is indicated by spontaneously occurring chromatid breaks, rearrangements, gaps .
For prenatal diagnosis, abnormal chromosome breakage analysis and genetic testing can be performed in amniotic fluid cells or in tissue from a chorionic villus biopsy.
Complications
major feature of the phenotype of FA is the propensity for cancer.
The most frequent solid tumors are squamous cell carcinomas of the head, neck, and upper esophagus, followed by carcinomas of the vulva and/or anus, cervix, and lower esophagus. Human papilloma virus is suspected in the pathogenesis.
Benign and malignant liver tumors occur (adenomas, hepatomas) are usually associated with androgen therapy for aplastic anemia.
Androgens are also implicated in the etiology of peliosis hepatis (blood-filled hepatic sinusoids). Peliosis hepatis is reversible when androgen therapy is discontinued, and tumors may regress.
Approximately 15% of patients with FA are at risk for acute leukemia by the age of 35 yr.
Treatment
A hematologist should supervise patients with FA. If the hematologic findings are stable and there are no transfusion requirements, observation is indicated.
If growth velocity is below expectations, endocrine evaluation is needed to identify growth hormone deficiency or hypothyroidism.
Screening for glucose intolerance and hyperinsulinemia should be performed annually or biannually, depending on the degree of hyperglycemia found on initial testing.
Blood counts should be performed every 1-3 mo; bone marrow aspiration and biopsy are indicated annually for leukemia and MDS .
Patients should be assessed for solid tumors at least annually. Beginning at menarche, female patients should be screened annually for gynecologic cancer. Administration of human papilloma virus quadrivalent vaccine to prevent squamous cell carcinoma is currently advised.
Hematopoietic stem cell transplantation is the only curative therapy for the hematologic abnormalities.
Androgens produce a response in 50% of patients, heralded by reticulocytosis and a rise in hemoglobin within 1-2 mo.
The beneficial effect of adding low-dose prednisone to androgens is controversial, but when administered orally every second day, they may counter androgen-induced growth acceleration and prevent thrombocytopenic bleeding by promoting vascular stability.
Granulocyte colony-stimulating factor (G-CSF) can usually induce an increase in the absolute neutrophil count and occasionally may boost platelet counts and hemoglobin levels.
Combination therapy consisting of G-CSF given subcutaneously daily or every 2 days along with erythropoietin given subcutaneously or IV 3 times/ wk results in improved neutrophil counts in almost all patients and a sustained rise in platelets and hemoglobin levels in approximately onethird of patients, although most patients lose the response after 1 yr owing to progression of marrow failure.