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Bone Marrow Failure

October 18, 2018

Disease summary:

Bone Marrow Failure is a clinically and genetically heterogeneous collection of diseases affecting hematopoiesis, resulting in reduced or abnormal production of one or more of the three blood cell types (red blood cell, white blood cell and platelets). Symptoms and onset vary greatly depending on the gene mutated and the nature of the mutation, but most cases have severe clinical implications from infancy or early childhood.

The main inherited bone marrow failure syndromes are Fanconi anemia (FA), Dyskeratosis congenita, Diamond Blackfan anemia and Shwachman Diamond syndrome. Many bone marrow failure disorders are additionally associated with an increased risk of cancer such as leukaemia and solid tumors1. Bone marrow failure can affect other systems of the body and patients may also display skeletal and organ abnormalities and disorders of the cardiovascular and central nervous system.

Other bone marrow failure disorders with multiple possible genetic origins include severe congenital neutropenia (SCN), thrombocytopenia and autoimmune lymphoproliferative syndrome. SCN is characterized by profound neutropenia diagnosed early in life and complicated by recurrent severe and life-threatening bacterial infections2. Thrombocytopenia usually presents in infancy or early childhood, most commonly with intensive and frequent mucosal bleeding, intermittent petechiae and purpura, and recurrent bacterial and viral infections.3

  • Autosomal dominant
  • Autosomal recessive
  • X-linked

FA: 1/100,000; carrier frequency is 1/100 in Ashkenazi Jewish, Spanish Gypsy, and black South African4

Dyskeratosis congenita: 1 in 1,000,0005

SCN: 2-3/1,000,000

Diamond Blackfan anemia: 1:100,000 and 1: 200,000

Thrombocytopenia: 4.6-5.3/100,000 in Sweden 9,5/100,00 in US, 1.6/1,00,00 worldwide

  • Pallor, lethargy
  • Recurrent infections (neutropenia)
  • Excessive bleeding or bruising (thrombocytopenia)
  • Abnormal skin pigmentation
  • Enlarged spleen, also other organs
  • Skeletal abnormalities
  • Growth retardation
  • Malignancies 
  • Low count or abnormality of one or more type of blood cell or platelet in peripheral blood
  • Abnormal Bone marrow aspirate)
  • Disease-specific cytological testing e.g. the chromosome breakage assay for FA6,7
  • Detection of a pathogenic variant in candidate gene/s
  • Hematopoietic stem cell transfer8,9
  • Blood transfusion
  • Corticosteroid treatment (Diamond Blackfan anemia)10
  • Hematopoietic growth factors e.g. recombinant human granulocyte colony-stimulating factor (SCN) 2,11
  • Acquired anemia12
  • Autoimmune disease12
  • Leukemia and Melyodysplasic syndromes12

To confirm bone marrow failure, CENTOGENE offers the following tests:

  • Bone marrow failure NGS panel or NGS panel plus
  • Bone marrow failure NGS panel or NGS panel plus + CNV which includes sequencing of the genes and additionally detection of large deletions and duplications from the NGS data
  • Bone marrow failure NGS panel genomic
  • Bone marrow failure deletion/duplication testing using MLPA/qPCR

Step 1: Bone Marrow Failure NGS Panel

Step 2: Bone Marrow Failure  NGS Panel + CNV which includes full gene sequencing and additionally detection of large deletions and duplications from the NGS data.   

  • Individuals with any of the symptoms of Bone Marrow Failure, regardless of family history, especially infants.
  • Individuals with a positive family history of Bone Marrow Failure


Confirmation of a clinical diagnosis through genetic testing of Bone Marrow Failure can allow for genetic counseling and may direct medical management, particularly in infants and young children.