Clinical Guidance

The primary clinical features of Fanconi anemia (FA) include physical abnormalities, progressive bone marrow failure manifest as pancytopenia, and cancer susceptibility; however, some individuals with FA have neither physical abnormalities nor bone marrow failure.

Table 2.

Fanconi Anemia: Frequency of Select Features

Feature | % of Persons w/Feature

Growth deficiency | 65%

Abnormal skin pigmentation | 40%

Skeletal malformations of upper limbs | 40%

Skeletal malformations of lower limbs | 5%

Microcephaly | 20%-25%

Kidney/ urinary tract anomalies | 20%-25%

Anomalies of internal external genitalia | Males: 25%Females: 2%

Endocrine disorders | 50%-75%

Ocular manifestations | 15%

Hearing loss | 10%

Developmental delay/ intellectual disability | 10%

Congenital heart defect | 6%

Gastrointestinal anomalies | 5%

Source: GeneReviews — "Fanconi Anemia"

Differential Diagnosis

Cells derived from individuals with other chromosome breakage syndromes may also exhibit high rates of spontaneous chromosome breakage; however, cells derived from individuals with Fanconi anemia (FA) exhibit increased chromosome breakage in response to diepoxybutane (DEB) and mitomycin C (MMC). Such chromosomal fragility is seen in few disorders but may be observed in cells derived from some, but not all, individuals with Seckel syndrome or Nijmegen breakage syndrome. In individuals with overlapping phenotypes, molecular genetic testing is necessary to confirm a diagnosis. See for selected examples of chromosome breakage syndromes and other disorders to consider in the differential diagnosis of FA. Table 5. Fanconi Anemia: Differential Diagnosis

Source: GeneReviews — "Fanconi Anemia"

Clinical Guidance

Blood transfusions. Blood products should be cytomegalovirus (CMV) safe and irradiated. To reduce the chances of sensitization, family members must not act as blood donors. Once an individual requires transfusions, the individual should be referred for transplantation. Toxic agents to avoid include smoking, secondhand smoke, and alcohol, which have been implicated in tumorigenesis. Excessive sun exposure. Sunscreen and sun-protective clothing should be used to limit UV exposure. Unsafe sex practices increase the risk for HPV-associated malignancy. Radiographic studies for the purpose of surveillance should be minimized in the absence of clinical indications. However, baseline skeletal surveys may be considered, in order to document bony anomalies that may lead to problems with age, such as anomalies of the wrist, hip, and vertebrae.

Source: GeneReviews — "Fanconi Anemia"

Therapies Under Investigation

Gene therapy. Several early phase clinical trials of FANCA gene therapy using lentiviral vectors were conducted at sites worldwide, including Stanford University and University of Washington/ Fred Hutchinson Cancer Research Center in the United States, Hospital Universitari Vall d'Hebron Research Institute in Spain, and Shenzhen Geno-Immune Medical Institute in China. All of these trials are now terminated or no longer actively recruiting. Separately, the US National Heart, Lung, and Blood Institute completed a Phase I trial of retroviral vector transduction of autologous CD34+ stem cells in individuals with FANCC-related FA (results pending).

Source: GeneReviews — "Fanconi Anemia"