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Fanconi anemia (FA) is a rare autosomal recessive (or X-linked) genetic disorder characterized by:

Progressive bone marrow failure (aplastic anemia)
Congenital anomalies (skeletal, renal, cardiac, facial)
Cancer predisposition, especially acute myeloid leukemia (AML) and solid tumors </aside>

It is a DNA repair disorder affecting the FA/BRCA pathway, critical for genome stability.

Fanconi anemia (Year of the Zebra 2025)

https://www.youtube.com/watch?v=fUsRtNULM14&t=229s

Etiology

Genetic Basis	Details
Genes involved	>20 FA genes (e.g., FANCA, FANCC, FANCG, FANCD2, FANCB)
Inheritance	Most commonly autosomal recessive; FANCB is X-linked
Pathogenesis	Defective repair of DNA interstrand crosslinks → chromosomal breakage and genomic instability

Epidemiology

Incidence: ~1 in 100,000–250,000 live births
Carrier frequency: ~1 in 300
Higher prevalence in Ashkenazi Jews and Afrikaners (due to founder mutations)

Clinical Features

1. Hematologic (usually first recognized)

Pancytopenia (progressive marrow failure)
Presents typically between 5–10 years
May initially show thrombocytopenia or macrocytic anemia

2. Congenital Anomalies (seen in ~70–80%)

System	Examples
Skeletal	– Thumb/radial ray defects (e.g., absent/thumb hypoplasia, absent radius)
– Short stature, scoliosis
Skin	Café-au-lait spots, hyper-/hypopigmentation
Renal	Horseshoe kidney, renal agenesis, duplication
Cardiac	Septal defects, aortic anomalies
Gastrointestinal	Esophageal atresia, imperforate anus
Neurodevelopmental	Microcephaly, intellectual disability
Genital	Hypoplasia, ambiguous genitalia (esp. in males)