(1) typical physical anomalies, but normal hematologic findings;
(2) normal physical features, but abnormal hematologic findings; or
(3) physical anomalies and abnormal hematologic findings
The most common anomaly is hyperpigmentation of the trunk, neck, and intertriginous areas, as well as café-au-lait spots and vitiligo, alone or in combination.
Most patients have short stature. Growth failure may be associated with abnormal growth hormone secretion, or with hypothyroidism. Absent radii and hypoplastic, supernumerary, bifid, or absent thumbs are common. Anomalies of the feet, congenital hip dislocation, and leg abnormalities are seen. Males may have an underdeveloped penis; undescended, atrophic, or absent testes; and hypospadias or phimosis. Females can have malformations of the vagina, uterus, and ovary. Many patients have a Fanconi “facies,” including microcephaly, small eyes, epicanthal folds, and abnormal shape, size, or positioning of the ears.
Approximately 10% of patients are mentally retarded. Ectopic, pelvic, or horseshoe kidneys are detected by imaging, as well as duplicated, hypoplastic, dysplastic, or absent organs.
Marrow failure usually ensues in the 1st decade of life.
Thrombocytopenia often appears initially, with subsequent onset of granulocytopenia and then macrocytic anemia.
Severe aplasia develops in most cases, but its full expression is variable and evolves over a period of mo to yr. The marrow becomes progressively hypocellular and fatty, similar to severe acquired aplastic anemia.
A hematologist using a multidisciplinary approach should supervise patients. If the hematologic findings are stable and there are no transfusion requirements, observation is indicated.
Subspecialty consultations can be arranged during this interval. If growth velocity is below expectations, endocrine evaluation is needed to identify growth hormone deficiency or hypothyroidism. Glucose intolerance and hyperinsulinemia should be screened for annually or biannually, depending on the degree of hyperglycemia found on initial testing. Patients should be assessed for cancer at least annually.
The premise for gene therapy in Fanconi anemia is based on the assumption that corrected hematopoietic cells offer a growth advantage. Attempts at gene therapy have been disappointing, possibly due to the type of vector, but also because of the fragility and impaired proliferative function of the hematopoietic progenitors