# Inherited Bone Marrow Failure Syndromes

> Inherited bone marrow failure for NEET-PG Medicine covers Fanconi anaemia, Diamond-Blackfan anaemia and dyskeratosis congenita, and how to tell them apart.

- Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/inherited-bone-marrow-failure-syndromes
- Exam / course: NEET-PG · Subject: Medicine
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-15
- Last updated: 2026-10-15
- Reference basis: Nathan and Oski's Hematology and Oncology of Infancy and Childhood; Harrison's Principles of Internal Medicine
- How to cite: "Inherited Bone Marrow Failure Syndromes", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/inherited-bone-marrow-failure-syndromes

## Direct answer

Inherited bone marrow failure syndromes are genetic disorders in which the marrow fails to produce adequate blood cells, usually in childhood. Classic examples are Fanconi anaemia, a DNA repair defect with skeletal anomalies; Diamond-Blackfan anaemia, a ribosomopathy causing pure red cell aplasia; and dyskeratosis congenita, a telomere disorder with skin and nail changes. All carry a raised malignancy risk and must be separated from acquired aplastic anaemia.

## What you must remember

- **Fanconi anaemia:** usually autosomal recessive, a DNA repair defect confirmed by chromosomal breakage tests with diepoxybutane or mitomycin C.
- **Fanconi features:** radial ray or thumb anomalies, café-au-lait spots, short stature, renal and skeletal malformations and microcephaly.
- **Fanconi malignancy:** a very high risk of acute myeloid leukaemia and squamous cell carcinoma, so long-term surveillance is needed.
- **Diamond-Blackfan anaemia:** pure red cell aplasia presenting in infancy, with macrocytosis, normal white cell and platelet counts and raised erythrocyte adenosine deaminase.
- **Diamond-Blackfan genetics:** ribosomal protein gene mutations, with RPS19 the most commonly mutated gene.
- **Diamond-Blackfan treatment:** corticosteroids are used first, with transfusion, chelation and transplantation as later options.
- **Dyskeratosis congenita triad:** reticular skin pigmentation, nail dystrophy and oral leukoplakia, with bone marrow failure developing later.
- **Dyskeratosis testing:** telomere length measurement confirms the diagnosis, and X-linked DKC1 is classically the most frequently mutated gene.

## Matching the syndrome to the child

A 6-year-old boy with short stature, a hypoplastic thumb and café-au-lait spots has falling platelet and white cell counts. The physical clues point to a specific syndrome before any test is reported.

| Feature | Fanconi anaemia | Diamond-Blackfan anaemia | Dyskeratosis congenita |
|---|---|---|---|
| Basis | DNA repair, autosomal recessive | Ribosomal protein genes | Telomere biology, X-linked DKC1 common |
| Presentation | Marrow failure in childhood | Anaemia in infancy | Triad of skin, nails and mucosa |
| Physical clues | Thumb anomalies, café-au-lait spots | Thumb and craniofacial anomalies | Nail dystrophy, leukoplakia |
| Key test | Chromosomal breakage | Raised erythrocyte adenosine deaminase | Telomere length |

The physical clues identify the syndrome before the tests, so the history of skin, limbs and growth comes first, and the test order follows from it. The chromosomal breakage test is the confirmatory step for Fanconi anaemia, and it is done even when physical anomalies are absent. Family history of early marrow failure or cancer adds weight, because several of these syndromes are inherited.

## Where the exam tries to catch you

Most lost marks come from treating an inherited syndrome as acquired aplastic anaemia, or from ignoring a normal-looking child.

- **Trap:** Treating every childhood marrow failure as acquired aplastic anaemia. — **Correct:** Fanconi anaemia responds poorly to immunosuppression, so the inherited diagnosis must be confirmed first.
- **Trap:** Excluding Fanconi anaemia because the child has no obvious anomalies. — **Correct:** Many patients have few physical clues, so the chromosomal breakage test is needed regardless.
- **Trap:** Using a normal white count to exclude Diamond-Blackfan anaemia. — **Correct:** It is pure red cell aplasia, so white cells and platelets are typically normal, and raised erythrocyte adenosine deaminase supports the diagnosis.
- **Trap:** Confusing dyskeratosis congenita with Fanconi anaemia on nail changes alone. — **Correct:** The triad of skin pigmentation, nail dystrophy and leukoplakia with telomere testing is the distinguishing approach.

## Frequently asked questions

### What is the chromosomal breakage test used for in Fanconi anaemia?

The chromosomal breakage test, using diepoxybutane or mitomycin C, confirms Fanconi anaemia by showing increased chromosomal fragility in lymphocytes. It is the key confirmatory test, even when physical anomalies are absent.

### Which features distinguish Diamond-Blackfan anaemia?

Diamond-Blackfan anaemia is a pure red cell aplasia presenting in infancy, with normal white cell and platelet counts. Raised erythrocyte adenosine deaminase, macrocytosis and congenital anomalies such as thumb malformations support the diagnosis.

### Which gene is most commonly mutated in Diamond-Blackfan anaemia?

RPS19 is the most commonly mutated gene in Diamond-Blackfan anaemia, a ribosomal protein gene whose defect causes a ribosomopathy. Other ribosomal protein genes account for a smaller proportion of patients.

### What is the classic triad of dyskeratosis congenita?

The classic triad of dyskeratosis congenita is reticular skin pigmentation, nail dystrophy and oral leukoplakia, with bone marrow failure developing later. Telomere length testing confirms the diagnosis, and X-linked DKC1 is classically the most frequently mutated gene.

### How is inherited bone marrow failure treated?

Haematopoietic stem cell transplantation is the main curative option for inherited bone marrow failure, with the choice depending on the syndrome and donor. Corticosteroids are used first in Diamond-Blackfan anaemia, while androgens are used in selected cases, per current guidance.