Fanconi's Anemia: New Insights

Clinical Features

FA was first reported in 1927 by Dr. Guido Fanconi,^[2] a Swiss pediatrician, who described 3 siblings with short stature, hypogonadism, skin pigmentation, and aplastic pancytopenia. Subsequently, FA has been characterized as a rare autosomal recessive disorder (prevalence of 1-5 per 1 million) characterized by progressive bone marrow failure, developmental anomalies, increased incidence of myelodysplasia (MDS), and predisposition to malignancy, especially acute myeloid leukemia (AML).^[3]

Patients with FA usually present by the end of the first decade of life (median age, 8 years), but have been diagnosed from birth to the fifth decade. Approximately 75% of affected individuals will have congenital anomalies (see Table ). Skeletal defects include radial ray, hip, vertebral, and rib anomalies, and they are present in about 70% of patients. Short stature and dermatologic, genitourinary, and ophthalmic anomalies are also quite common. Less frequent birth defects include neurologic (eg, hydrocephalus, developmental disabilities, or deafness), gastrointestinal (duodenal atresia, esophageal atresia, or imperforate anus), and cardiac abnormalities. It is important to realize that about one third of patients will have no abnormalities.^[4]

The hematologic abnormalities of FA are of greatest clinical significance, and often present early in life. At birth, the complete blood count is frequently normal. A macrocytic anemia develops, which usually precedes the onset of thrombocytopenia and neutropenia. Pancytopenia manifests itself at a median age of 7 years.

Clonal abnormalities of bone marrow progenitors are also common, with monosomy 5 and 7 reported in FA patients who have developed MDS/AML.^[5] Malignancy is an associated clinical feature of FA. Approximately 6% of patients with FA will develop MDS; 10% will develop AML; and 5% will develop cancers of the head/neck, esophagus, cervix, vulva, skin (nonmelanoma), brain, and other sites.^[6] The prognosis for FA patients is poor, with median survival projected between 20 and 30 years of age.

Cite this: Topics in Pediatric Leukemia -- Fanconi's Anemia: New Insights - Medscape - Apr 06, 2005.

Congenital Anomalies Associated With FA
Congenital Anomaly	Approximate Percentage of FA Patients Affected
Skeletal (radial ray, hip, rib, and vertebral) anomalies	70%
Skin pigmentation (café au lait, hypopigmentation)	60%
Short stature	60%
Eyes (hypertelorism, hypotelorism, microphthalmia, ptosis, or epicanthal folds)	35% to 40%
Genitourinary anomalies (ectopic kidney, horseshoe kidney, dysplastic kidney, or hypospadias)	35%
Neurologic anomalies (microcephaly, mental retardation, hydrocephalus, or deafness)	30%
Gastrointestinal anomalies (imperforate anus, esophageal atresia, duodenal atresia)	10% to 15%
Cardiac anomalies (patent ductus arteriosus, atrial septal defects, ventricular septal defects, tetralogy of Fallot)	10% to 15%
No anomalies	30%

FA = Fanconi's anemia

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