Neutropenia [33 genes]

Neutropenias are conditions characterized by specific defects in neutrophils that can produce congenital neutropenia, whether or not associated with syndromic forms. This group of pathologies that affect innate immunity can also have an autoimmune cause. There are forms of severe congenital neutropenia and cyclic neutropenia that only affect neutrophils, while other types produce neutropenia associated with other hematopoietic defects with or without extra-hematopoietic manifestations.

• Disseminated, recurrent infections
• Poor wound healing
• Extra-hematopoietic manifestations
• Onset: childhood

It is estimated that congenital neutropenia has a prevalence of 1/250,000 inhabitants, although the prevalence of each of the genetic subtypes is unknown, with few families described. The most common cause of congenital neutropenia is due to genetic defects in the ELANE gene.

• Differential diagnosis and genetic counseling
• Hematopoietic stem cell transplantation (HSCT)
• G-CSF therapy
• Prophylactic antibacterials

Identifying a causal genetic defect in the genes of this panel allows a precise molecular diagnosis and adequate genetic counseling to be offered.

Neutropenias are conditions characterized by specific defects in neutrophils that can produce congenital neutropenia, whether or not associated with syndromic forms. For example, germline mutations that alter neutrophil elastase (encoded by ELANE) can cause severe congenital neutropenia and cyclic neutropenia, while mutations in HAX1 can cause autosomal recessive congenital neutropenia. Pathogenic mutations in CSF3R, GFI1, WAS, and RAC2 produce neutropenia associated with other hematopoietic defects. Severe congenital neutropenias (SNC) are low-prevalence pediatric hematologic disorders characterized by germline mutations in genes that lead to failure of granulocyte maturation in the marrow. Affected children have an increased risk of infections and the development of leukemia. Syndromic conditions present with hematopoietic or extra-hematopoietic manifestations, and the tissues or organs affected include, among others:

• Heart: G6PC3, TAZ.
• Urogenital system: G6PC3.
• Bones and the exocrine pancreas: Shwachman-Diamond syndrome.
• Skin: LAMTOR2
• Liver: glycogen storage; SLC37A4.