Description

• A rare hematologic disorder characterized by recurrent fevers, mouth ulcers, and infections attributable to regularly recurring severe neutropenia
• Although inherited in an autosomal dominant pattern, mutations in the gene for neutrophil elastase (ELA-2), sporadic mutations can occur; characterized by neutropenia that recurs every 14 to 35 days, with 90% of patients exhibiting a cycle of 21 days
• During the neutropenic period, blood neutrophil levels fall to <0.2 × 10⁹/L for 3 to 5 days, before increasing to near the lower limit of normal, ~2 × 10⁹/L.

Epidemiology

• Most patients present before the age of 5 years:
  • 32% are <1 year of age.
  • 27% are between ages 1 and 5 years.
• Occurs equally in both sexes

Incidence
1 to 2 in a million people

Etiology and Pathophysiology

• Bone marrow during neutropenia demonstrates “maturation arrest” at the promyelocyte and myelocyte stage of development.
• At least 80% of cases of cyclic neutropenia are attributable to the mutations for neutrophil elastase (ELA-2/ELANE).
• This mutation results in accelerated apoptosis of neutrophil progenitors, making neutrophil production inefficient.
• It is not known if any other mutations can cause this disease.
• The cause of acquired cyclic neutropenia is unknown.

Genetics

• Autosomal dominant disorder with full penetrance but varying severity of clinical manifestations (expression)
• Most commonly sporadic
• Due to mutations in the gene for neutrophil elastase (ELA-2 or ELANE) on chromosome 19p13.3 (1)[A]

Risk Factors

• Family history is predictive, although patients proven to have the (ELA) mutation will lack positive family history due to subclinical presentation among family members, new mutation, or variability in expression.
• Neutropenia may also be inherited. This condition is called ethnic benign neutropenia because it is not associated with any type of infection.

General Prevention

Genetic counseling