Overview
Definition
An autosomal recessive DNA repair disorder characterized by congenital abnormalities, progressive bone marrow failure, and predisposition to cancer.
Epidemiology
Prevalence ~1 in 160,000. Most common inherited bone marrow failure syndrome.
Etiology & Risk Factors
- Mutations in FANC genes involved in homologous recombination DNA repair, leading to chromosome fragility
Clinical Symptoms
- Short stature
- Malformed or absent thumbs and radius bones
- Café-au-lait spots
- Microcephaly
- Progressive pancytopenia
Clinical Approach
Diagnosis
- Chromosomal breakage test using Diepoxybutane (DEB) or Mitomycin C (MMC) in blood lymphocytes
Management
- Allogeneic Hematopoietic Stem Cell Transplantation (definitive treatment for marrow failure)
- Androgen therapy for cytopenias
- Cancer surveillance
Complications
- Acute Myelogenous Leukemia (AML)
- Squamous cell carcinomas of head/neck/vulva
- Aplastic anemia