The biological basis for the substantial difference in risk of leukemic evolution for CyN (Cyclic neutropenia) versus SCN (Neutropenia, severe congenital, 1) is not known (PMID:25427142). CyN patients show an oscillation of ANC (absolute neutrophil count) with 3 weekly periods of severe neutropenia (PMID:23463630). The typical morphological finding is a myeloid maturation arrest at the promyelocyte/myelocyte stage seen in conventional bone marrow smears. Heterozygous ELANE mutations are present in 80–100% of individuals with CyN and in 35–63% of SCN cases (PMID:21425445).
Cyclic neutropenia is a rare disease characterized by regular 21-day cyclic fluctuations in the number of blood neutrophils, monocytes, eosinophils, lymphocytes, platelets, and reticulocytes. The recurrent severe neutropenia causes patients to experience periodic symptoms of fever, malaise, mucosal ... Cyclic neutropenia is a rare disease characterized by regular 21-day cyclic fluctuations in the number of blood neutrophils, monocytes, eosinophils, lymphocytes, platelets, and reticulocytes. The recurrent severe neutropenia causes patients to experience periodic symptoms of fever, malaise, mucosal ulcers, and, rarely, life-threatening infections. The disease occurs both as a congenital disorder and in an acquired form, with essentially identical phenotypic presentations (summary by Migliaccio et al., 1990).
Hahneman and Alt (1958) described a 29-year-old man who from an early age had neutropenia that recurred every 21 days and was accompanied by infection. Complete remission occurred at age 18 years. The man's daughter was seen at ... Hahneman and Alt (1958) described a 29-year-old man who from an early age had neutropenia that recurred every 21 days and was accompanied by infection. Complete remission occurred at age 18 years. The man's daughter was seen at the age of 2 years with similar periodic disease recurring every 14 days. Torrioli-Riggio (1958) also reported cases. Morley et al. (1967) described 20 cases in 5 families. Clinical manifestations usually began in childhood and improved thereafter. The commonest were fever, oral ulcerations, and skin infections. Neutropenia occurred at intervals of 15 to 35 days. It was often accompanied by monocytosis and sometimes by anemia, eosinophilia, or thrombocytopenia. Male-to-male transmission occurred. Peng et al. (2000) described a family in which all 4 male members, the father and 3 sons, had hereditary cyclic neutropenia starting in childhood with a cycle of approximately 21 days. Recurrent mucosa and skin infections with fever had occurred frequently, but gradually decreased in severity as they reached adulthood. Monocytosis was found during the neutrophil nadirs in all 4 patients. Decreased sperm count and motility were demonstrated in the 2 elder sons. Chromosome analysis showed a pericentric inversion of the Y chromosome in all of the men. The chromosome anomaly was inv(Y)(p11.2;q11.23). Krance et al. (1982) reported a family in which 7 persons in 4 sibships had cyclic neutropenia. One unaffected member of the family who was in the process of bone marrow transplantation as treatment for acute lymphoblastic leukemia in relapse, acquired cyclic neutropenia from her histocompatible donor sib. While cyclic hematopoiesis is commonly described as 'benign,' Palmer et al. (1996) found that 4 affected children in 3 of 9 families died of Clostridium or E. coli colitis, documenting the need for urgent evaluation of abdominal pain. Misdiagnosis with other neutropenias was common but can be avoided by serial blood counts in index cases.
Horwitz et al. (1999) identified 7 different single-basepair substitutions in the ELANE gene (e.g., 130130.0001-130130.0005), encoding neutrophil elastase (ELA2). In each of 13 families studied, a mutation in ELANE was found on a unique haplotype; the haplotype carrying ... Horwitz et al. (1999) identified 7 different single-basepair substitutions in the ELANE gene (e.g., 130130.0001-130130.0005), encoding neutrophil elastase (ELA2). In each of 13 families studied, a mutation in ELANE was found on a unique haplotype; the haplotype carrying a new mutation in a sporadic case was also unique. Neutrophil elastase is a target for protease inhibition by alpha-1-antitrypsin (AAT; 107400), and its unopposed release destroys tissue at sites of inflammation. Horwitz et al. (1999) hypothesized that a perturbed interaction between neutrophil elastase and serpins or other substrates may regulate mechanisms governing the clock-like timing of hematopoiesis.