Other Bone Marrow Failure Syndromes

Baby lying in a crib holding an adults finger

There are a variety of other inherited bone marrow failure syndromes. We have listed some here, but not all are listed. Please reach out to our team if you are interested in learning more about these or any other inherited bone marrow failure syndrome.

Amegakaryocytic Thrombocytopenia (Amega)

Individuals with amega, also sometimes called congenital amegakaryotic thrombocytopenia (CAMT), develop bruising during their first year of life, due to decreased production of platelets by the bone marrow. Their physical appearance is otherwise normal. Amega can be caused by genetic variants in the MPL gene. Males and females are equally affected.

What are the major findings on physical examination?

  • Bruises, bleeding, and tiny spots of bleeding into the skin ("petechiae")

What is the age at diagnosis?

  • Anytime from birth through childhood
  • Most individuals are younger than 1 month of age when the diagnosis is made

What is the natural progression of bone marrow failure in individuals with amega?

  • Some individuals with amega can live for years without bone marrow failure while others develop symptoms earlier.
  • Bone marrow failure means the number of blood cells is too low because the bone marrow has stopped producing enough mature cells.
  • Individuals typically start with low platelet counts and may progress to low counts in two or more types of blood cells (also known as aplastic anemia):
    • Low red blood cell count (anemia)
    • Low platelet count (thrombocytopenia)
    • Low white blood cell count (leukopenia)

What types of cancer are individuals with amega at higher risk of developing?

  • Leukemia (cancer of the blood and bone marrow)

How is amega specifically diagnosed?

  • Clinical findings
  • Genetic testing

Genetics

  • Amega is caused by variants in the MPL gene and is usually inherited in an autosomal recessive manner. This means that individuals need both copies of the gene variant to have amega.

Severe Congenital Neutropenia (SCN)

Individuals with SCN have very low white blood cell counts. Since white cells help the body to fight off infection, children with this disorder can develop serious infections during infancy. The physical appearance is normal. Males and females are equally affected.

What are the major findings on physical examination?

  • Individuals with SCN have normal physical examinations.

What is the age at diagnosis?

  • The diagnosis is usually made in the first year of life but can also be made later.

What is the natural progression of bone marrow failure in individuals with SCN?

  • The bone marrow of individuals with SCN fails to produce a type of white blood cell known as a neutrophil. Neutrophils are essential in fighting bacterial infections.

What types of cancer are individuals with SCN at higher risk of developing?

  • Leukemia (cancer of the blood and bone marrow)

How is SCN specifically diagnosed?

  • By performing a blood count and a bone marrow examination, the specific absence of neutrophil white cells can be detected.
  • Genetic testing

Genetics

  • SCN can be caused by variants in the ELANE (formerly ELA2) gene and is usually inherited in an autosomal dominant manner. This means that individuals only need one copy of the gene variant to have SCN.
  • In some families, SCN can be caused by variants in the HAX1 gene and is usually inherited in an autosomal recessive manner. This means that individuals need both copies of the gene variant to have SCN. This form of SCN is also known as Kostmann Syndrome.
  • Other rare disease-causing gene variants occur in: GFI1 (dominant), G6PC3 (recessive), and THC1/WAS (X-linked recessiveExternal Web Site Policy).

Thrombocytopenia Absent Radii (TAR)

Individuals with TAR are missing the radius bone from each lower arm. The radius is one of the two bones in the lower arm and it runs from the elbow to the wrist on the side of the thumb. Bruising occurs due to decreased production of platelets (the cells which help the blood to clot) by the bone marrow and is usually apparent at birth. Males and females are affected equally.

What are the major findings on physical examination?

  • Missing radius bone from both lower arms
  • Abnormal thumbs
  • Small shoulders
  • Abnormal knees (bow legs or knock knees)

What is the age at diagnosis?

  • The diagnosis is almost always made at birth or prenatally.

What is the natural progression of bone marrow failure in individuals with TAR?

  • The illness begins with a low platelet count in infancy or childhood.
  • Most individuals with TAR have improvement in platelet counts with age.
  • Individuals with TAR do not typically develop aplastic anemia which is a condition seen in some of the other bone marrow failure disorders. Aplastic anemia occurs when all three types of blood cells (red cells, white cells, and platelets) are abnormally low because the bone marrow is not producing them.

What types of cancer are individuals with TAR at higher risk of developing?

  • There are a few case reports of leukemia (cancer of the blood and bone marrow) in people with TAR.

How is TAR specifically diagnosed?

  • The diagnosis is made by physical examination, in which the radius bones in the arms are found to be missing.
  • Low platelet count
  • Genetic testing

Genetics

  • TAR is associated with a deletion (absence) of part of chromosome 1 inherited from one unaffected parent; the other parental gene is identified by genetic variant in the RMB8A gene.

Syndromes with high risk of MDS and leukemia

  • SAMD9 and SAMD9L
    Patients with genetic variants in SAMD9 and SAMD9L can present with ataxia-pancytopenia syndrome, and MIRAGE. Patients may have low blood counts and can develop myelodysplastic syndrome.
  • MECOM
    Patients with radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) due to mutations in the MECOM gene can have arm abnormalities and low blood cells counts, particularly platelets. These patients are also at risk of developing myelodysplastic syndrome and leukemia.
  • ANKRD26
    Patients with mutations in ANKRD26 have autosomal dominant thrombocytopenia. Mutations in ANKRD26 lead to a problem with platelet production. These patients are risk of developing myelodysplastic syndrome and leukemia.
  • GATA2
    GATA2 deficiency is an autosomal dominant disorder that predisposes individuals to non-tuberculous mycobacterial infections and myelodysplastic syndrome. Patients have low monocytes (a type of white blood cell). The National Institute of Allergy and Infectious Diseases has an on-going study for patients with GATA2 deficiency.
  • RUNX1
    Familial platelet disorder is caused by autosomal dominant mutations in the RUNX1 gene. Patients have low platelets and a predisposition to developing acute myeloid leukemia. The National Human Genome Research Institute has an on-going study for patients with familial platelet disorder.
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How can I join?

Individuals with one of the inherited bone marrow failure syndromes and their family members are encouraged to participate.

Phone: 1-800-518-8474 to speak with the referral nurse
Email: NCI.IBMFS@westat.com