Related Subjects:
|Iron deficiency Anaemia
|Haemolytic anaemia
|Macrocytic anaemia
|Megaloblastic anaemia
|Microcytic anaemia
|Myelodysplasia
|Myelofibrosis
๐งฌ When diagnosing aplastic anaemia in a child, always consider Fanconi Anaemia if congenital malformations (e.g. absent or hypoplastic thumbs, radial anomalies on hand/forearm X-ray) are present.
โ ๏ธ Do not confuse Fanconi Anaemia (genetic bone marrow failure) with Fanconi Syndrome (renal tubular dysfunction).
๐ About
- Fanconi Anaemia (FA): A rare inherited bone marrow failure syndrome, usually autosomal recessive (some X-linked cases).
- Leads to progressive aplastic anaemia with pancytopenia.
- Associated with congenital malformations and markedly increased risk of haematological malignancies, especially Acute Myeloid Leukaemia (AML).
๐งช Etiology
- Mutations in DNA repair genes โ defective repair of interstrand crosslinks โ genomic instability.
- Cells show increased chromosomal breakage when exposed to agents like diepoxybutane (DEB) or mitomycin C.
๐ง Clinical Features
- Skeletal anomalies: Absent/hypoplastic thumbs, absent radii, short stature, microcephaly.
- Skin changes: Cafรฉ-au-lait spots, hyper/hypopigmented lesions.
- Bone marrow failure: Pancytopenia โ fatigue, pallor, infections, bleeding tendency.
- High risk of transformation into MDS โ AML.
๐ Investigations
- FBC: Pancytopenia.
- Serum ฮฑ-fetoprotein (sAFP): Often raised.
- Radiology: Hand/forearm X-rays showing radial ray anomalies.
- Chromosome breakage test: DEB or mitomycin C challenge reveals excessive chromosomal fragility.
โ ๏ธ Complications
- Progression to myelodysplastic syndrome and AML.
- Solid tumours, especially squamous cell carcinoma of the head, neck, or genital tract.
๐ฉบ Management
- Supportive: Transfusions, infection prophylaxis, growth factor support.
- Hematopoietic Stem Cell Transplant (HSCT): Only curative therapy for marrow failure in FA.
- Genetic counselling: Essential for families due to inheritance pattern.
- Surveillance: Lifelong cancer monitoring required.
Cases โ Fanconi Anaemia
- Case 1 โ Child with Pancytopenia and Short Stature:
A 7-year-old boy is referred with recurrent nosebleeds, fatigue, and frequent infections. He is below the 5th centile for height. FBC shows pancytopenia. Physical exam notes cafรฉ-au-lait spots and hypoplastic thumbs. Diagnosis: Fanconi Anaemia presenting with bone marrow failure.
- Case 2 โ Adolescent with Congenital Abnormalities:
A 13-year-old girl is evaluated for delayed puberty and primary amenorrhoea. She has a horseshoe kidney, microcephaly, and abnormal radial rays. Bloods show macrocytosis and mild anaemia. Family history reveals a cousin with similar skeletal anomalies. Chromosomal breakage test confirms the diagnosis. Diagnosis: Fanconi Anaemia with congenital anomalies.
- Case 3 โ Young Adult with Malignancy:
A 19-year-old male with known Fanconi Anaemia develops progressive oral ulcers and weight loss. Biopsy reveals squamous cell carcinoma of the oropharynx. He has had long-standing pancytopenia and required supportive transfusions. Diagnosis: Secondary malignancy (head and neck SCC) in Fanconi Anaemia.
Teaching Commentary ๐งฌ
Fanconi Anaemia is a rare autosomal recessive (or X-linked) DNA repair disorder leading to chromosomal instability. Classic features include progressive bone marrow failure, congenital anomalies (radial ray defects, renal abnormalities, microcephaly), cafรฉ-au-lait spots, and increased cancer risk. Patients often present in childhood with pancytopenia, but may also come to attention due to congenital anomalies. They are highly predisposed to acute myeloid leukaemia and squamous cell carcinoma of head/neck and genital tract. Diagnosis is via chromosomal breakage tests. Management includes supportive care, and the only curative therapy for marrow failure is allogeneic stem cell transplantation.
