# Fanconi Anaemia and Inherited Marrow Failure

> Fanconi anaemia and inherited marrow failure for NEET-PG Paediatrics, covering congenital anomalies, the chromosomal breakage test and malignancy risk.

- Canonical URL: https://prepelephant.com/topics/neet-pg/paediatrics/fanconi-anaemia-and-inherited-marrow-failure
- Exam / course: NEET-PG · Subject: Paediatrics
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-08
- Last updated: 2026-10-08
- Reference basis: Nathan and Oski's Hematology and Oncology of Infancy and Childhood; Nelson Textbook of Pediatrics
- How to cite: "Fanconi Anaemia and Inherited Marrow Failure", PrepElephant, https://prepelephant.com/topics/neet-pg/paediatrics/fanconi-anaemia-and-inherited-marrow-failure

## Direct answer

Fanconi anaemia is an inherited DNA repair disorder that causes progressive bone marrow failure, congenital anomalies and a high risk of leukaemia and solid tumours. It is usually diagnosed with the chromosomal breakage test, in which lymphocytes show excess breaks after exposure to DNA cross-linking agents such as mitomycin C or diepoxybutane. Pancytopenia typically appears in childhood, and haematopoietic stem cell transplantation is the main curative option.

## What you must remember

- **Inheritance:** mostly autosomal recessive, with rare X-linked forms; many complementation groups affect the FANC DNA repair pathway.
- **Radial anomalies:** absent or hypoplastic thumb and radius are classic, alongside café-au-lait spots, short stature and microcephaly.
- **Other anomalies:** renal and urinary tract malformations, hypogonadism and skin pigmentation; the absence of anomalies does not exclude the diagnosis.
- **Breakage test:** excess chromosomal breaks after mitomycin C or diepoxybutane confirm the diagnosis, and mosaic cases may need repeat testing.
- **Malignancy risk:** acute myeloid leukaemia, myelodysplasia, and squamous cell carcinomas of the head, neck and anogenital region.
- **Other inherited marrow failure:** Diamond-Blackfan anaemia (macrocytic, with erythroid aplasia), dyskeratosis congenita (nail dystrophy, leukoplakia, telomere defect) and Shwachman-Diamond syndrome (neutropenia with pancreatic insufficiency).

## A pathway that separates syndromic from acquired marrow failure

Evaluation separates syndromic marrow failure from acquired aplastic anaemia, because transplant conditioning and surveillance plans differ.

1. **Recognise the pattern:** progressive pancytopenia in a child with characteristic anomalies or family history warrants inherited marrow failure testing.
2. **Confirm with breakage:** perform the chromosomal breakage test with mitomycin C or diepoxybutane; a positive result confirms Fanconi anaemia.
3. **Sequence the genes:** identify the complementation group to guide counselling and family screening.
4. **Assess the marrow:** aspirate and biopsy for cellularity, dysplasia and clonal change, looking for early myelodysplasia.
5. **Screen organs and malignancy:** renal and skeletal ultrasound, endocrine review and examination of the head, neck and anogenital region.
6. **Plan transplant:** HLA typing of siblings, with reduced-toxicity conditioning because patients tolerate standard chemotherapy and radiation poorly.

Prenatal and newborn clues are often subtle, so a normal birth does not exclude the disorder. Early diagnosis matters because it changes transplant planning and cancer surveillance, which continues with regular examination of skin, oral cavity, anogenital region and blood counts.

## Where the exam tries to catch you

Marrow failure vignettes often hinge on a missing anomaly or an unexpected conditioning choice.

- **Trap:** diagnosing acquired aplastic anaemia without looking for anomalies — **Correct:** a breakage test should be considered in any child with pancytopenia and a suspicious feature.
- **Trap:** assuming normal radial anatomy excludes Fanconi anaemia — **Correct:** a minority of patients lack anomalies, so the breakage test decides.
- **Trap:** using standard high-dose conditioning for transplant — **Correct:** patients tolerate alkylators and radiation poorly, so modified conditioning is used.
- **Trap:** ignoring solid tumour risk after recovery — **Correct:** lifelong surveillance is needed for head, neck and anogenital cancers.

## Frequently asked questions

### What is the diagnostic test for Fanconi anaemia?

The chromosomal breakage test is the diagnostic test for Fanconi anaemia, measuring excess breaks in lymphocytes after exposure to mitomycin C or diepoxybutane. Genetic sequencing then identifies the complementation group for counselling.

### Which congenital anomalies suggest Fanconi anaemia?

Absent or hypoplastic thumb and radius, café-au-lait spots, short stature, microcephaly and renal anomalies are classic features of Fanconi anaemia. A child with pancytopenia and any such feature should prompt breakage testing.

### How does Fanconi anaemia differ from acquired aplastic anaemia?

Fanconi anaemia is inherited, often with congenital anomalies and a breakage defect, while acquired aplastic anaemia is usually immune-mediated in a child without these features. The distinction changes transplant conditioning and cancer surveillance.

### What is the main curative treatment for Fanconi anaemia?

Haematopoietic stem cell transplantation is the main curative treatment for marrow failure in Fanconi anaemia, ideally from a matched sibling donor. Conditioning is modified because patients are sensitive to chemotherapy and radiation.

### What are the main malignancies in Fanconi anaemia?

Acute myeloid leukaemia and myelodysplastic syndrome are the commonest haematological malignancies in Fanconi anaemia, while head, neck and anogenital squamous cell carcinomas are important solid tumours. Lifelong surveillance is recommended for these risks.