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Cyclical neutropenia

MedGen UID:
65121
Concept ID:
C0221023
Disease or Syndrome
Synonyms: Cyclic hematopoiesis; Cyclic Neutropenia
SNOMED CT: Periodic neutropenia (191347008); Cyclic hematopoiesis (191347008); Cyclical neutropenia (191347008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): ELANE (19p13.3)
 
HPO: HP:0040289
Monarch Initiative: MONDO:0008090
OMIM®: 162800
Orphanet: ORPHA2686

Disease characteristics

Excerpted from the GeneReview: ELANE-Related Neutropenia
ELANE-related neutropenia includes congenital neutropenia and cyclic neutropenia, both of which are primary hematologic disorders characterized by recurrent fever, skin and oropharyngeal inflammation (i.e., mouth ulcers, gingivitis, sinusitis, and pharyngitis), and cervical adenopathy. Infectious complications are generally more severe in congenital neutropenia than in cyclic neutropenia. In congenital neutropenia, omphalitis immediately after birth may be the first sign; in untreated children diarrhea, pneumonia, and deep abscesses in the liver, lungs, and subcutaneous tissues are common in the first year of life. After 15 years with granulocyte colony-stimulating factor treatment, the risk of developing myelodysplasia (MDS) or acute myelogenous leukemia (AML) is approximately 15%-25%. Cyclic neutropenia is usually diagnosed within the first year of life based on approximately three-week intervals of fever and oral ulcerations and regular oscillations of blood cell counts. Cellulitis, especially perianal cellulitis, is common during neutropenic periods. Between neutropenic periods, affected individuals are generally healthy. Symptoms improve in adulthood. Cyclic neutropenia is not associated with risk of malignancy or conversion to leukemia. [from GeneReviews]
Authors:
David C Dale  |  Vahagn Makaryan   view full author information

Additional descriptions

From OMIM
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).  http://www.omim.org/entry/162800
From MedlinePlus Genetics
Cyclic neutropenia is a disorder that causes frequent infections and other health problems in affected individuals. People with this condition have recurrent episodes of neutropenia during which there is a shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. The episodes of neutropenia are apparent at birth or soon afterward. For most affected individuals, neutropenia recurs every 21 days and lasts about 3 to 5 days.

Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses, so people with cyclic neutropenia typically develop recurrent infections of the sinuses, respiratory tract, and skin. Additionally, people with this condition often develop open sores (ulcers) in the mouth and colon, inflammation of the throat (pharyngitis) and gums (gingivitis), recurrent fever, or abdominal pain. People with cyclic neutropenia have these health problems only during episodes of neutropenia. At times when their neutrophil levels are normal, they are not at an increased risk of infection and inflammation.  https://medlineplus.gov/genetics/condition/cyclic-neutropenia

Clinical features

From HPO
Malaise
MedGen UID:
65412
Concept ID:
C0231218
Sign or Symptom
A feeling of general discomfort, weakness, or lack of health.
Cyclical neutropenia
MedGen UID:
65121
Concept ID:
C0221023
Disease or Syndrome
ELANE-related neutropenia includes congenital neutropenia and cyclic neutropenia, both of which are primary hematologic disorders characterized by recurrent fever, skin and oropharyngeal inflammation (i.e., mouth ulcers, gingivitis, sinusitis, and pharyngitis), and cervical adenopathy. Infectious complications are generally more severe in congenital neutropenia than in cyclic neutropenia. In congenital neutropenia, omphalitis immediately after birth may be the first sign; in untreated children diarrhea, pneumonia, and deep abscesses in the liver, lungs, and subcutaneous tissues are common in the first year of life. After 15 years with granulocyte colony-stimulating factor treatment, the risk of developing myelodysplasia (MDS) or acute myelogenous leukemia (AML) is approximately 15%-25%. Cyclic neutropenia is usually diagnosed within the first year of life based on approximately three-week intervals of fever and oral ulcerations and regular oscillations of blood cell counts. Cellulitis, especially perianal cellulitis, is common during neutropenic periods. Between neutropenic periods, affected individuals are generally healthy. Symptoms improve in adulthood. Cyclic neutropenia is not associated with risk of malignancy or conversion to leukemia.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCyclical neutropenia
Follow this link to review classifications for Cyclical neutropenia in Orphanet.

Conditions with this feature

Cyclical neutropenia
MedGen UID:
65121
Concept ID:
C0221023
Disease or Syndrome
ELANE-related neutropenia includes congenital neutropenia and cyclic neutropenia, both of which are primary hematologic disorders characterized by recurrent fever, skin and oropharyngeal inflammation (i.e., mouth ulcers, gingivitis, sinusitis, and pharyngitis), and cervical adenopathy. Infectious complications are generally more severe in congenital neutropenia than in cyclic neutropenia. In congenital neutropenia, omphalitis immediately after birth may be the first sign; in untreated children diarrhea, pneumonia, and deep abscesses in the liver, lungs, and subcutaneous tissues are common in the first year of life. After 15 years with granulocyte colony-stimulating factor treatment, the risk of developing myelodysplasia (MDS) or acute myelogenous leukemia (AML) is approximately 15%-25%. Cyclic neutropenia is usually diagnosed within the first year of life based on approximately three-week intervals of fever and oral ulcerations and regular oscillations of blood cell counts. Cellulitis, especially perianal cellulitis, is common during neutropenic periods. Between neutropenic periods, affected individuals are generally healthy. Symptoms improve in adulthood. Cyclic neutropenia is not associated with risk of malignancy or conversion to leukemia.
Phosphate transport defect
MedGen UID:
87455
Concept ID:
C0342749
Disease or Syndrome
Glycogenosis due to glucose-6-phosphatase deficiency (G6P) type b, or glycogen storage disease (GSD) type 1b, is a type of glycogenosis due to G6P deficiency (see this term).
3-Methylglutaconic aciduria type 2
MedGen UID:
107893
Concept ID:
C0574083
Disease or Syndrome
Barth syndrome is characterized in affected males by cardiomyopathy, neutropenia, skeletal myopathy, prepubertal growth delay, and distinctive facial gestalt (most evident in infancy); not all features may be present in a given affected male. Cardiomyopathy, which is almost always present before age five years, is typically dilated cardiomyopathy with or without endocardial fibroelastosis or left ventricular noncompaction; hypertrophic cardiomyopathy can also occur. Heart failure is a significant cause of morbidity and mortality; risk of arrhythmia and sudden death is increased. Neutropenia is most often associated with mouth ulcers, pneumonia, and sepsis. The nonprogressive myopathy predominantly affects the proximal muscles, and results in early motor delays. Prepubertal growth delay is followed by a postpubertal growth spurt with remarkable "catch-up" growth. Heterozygous females who have a normal karyotype are asymptomatic and have normal biochemical studies.

Professional guidelines

Recent clinical studies

Etiology

Arun AK, Senthamizhselvi A, Hemamalini S, Edison ES, Korula A, Fouzia NA, George B, Mathews V, Balasubramanian P
J Clin Pathol 2018 Dec;71(12):1046-1050. Epub 2018 Aug 31 doi: 10.1136/jclinpath-2018-205235. PMID: 30171085

Diagnosis

Arun AK, Senthamizhselvi A, Hemamalini S, Edison ES, Korula A, Fouzia NA, George B, Mathews V, Balasubramanian P
J Clin Pathol 2018 Dec;71(12):1046-1050. Epub 2018 Aug 31 doi: 10.1136/jclinpath-2018-205235. PMID: 30171085
Keogan MT
Clin Exp Immunol 2009 Apr;156(1):1-11. Epub 2008 Dec 11 doi: 10.1111/j.1365-2249.2008.03857.x. PMID: 19210521Free PMC Article
Haurie C, Dale DC, Mackey MC
Exp Hematol 1999 Mar;27(3):401-9. doi: 10.1016/s0301-472x(98)00061-7. PMID: 10089901
Wong SN, Tam AY, Yung RW, Kwan EY, Tsoi NN
Acta Paediatr Scand 1991 May;80(5):515-20. doi: 10.1111/j.1651-2227.1991.tb11895.x. PMID: 1872174
Morley AA, Carew JP, Baikie AG
Br J Haematol 1967 Sep;13(5):719-38. doi: 10.1111/j.1365-2141.1967.tb08838.x. PMID: 6050865

Therapy

De Souza DC, Mackey MC
J Math Biol 2019 May;78(6):1637-1679. Epub 2019 Jan 12 doi: 10.1007/s00285-018-1322-y. PMID: 30637475
Dale DC, Mackey MC
Bull Math Biol 2015 May;77(5):739-57. Epub 2014 Sep 12 doi: 10.1007/s11538-014-9995-x. PMID: 25213154Free PMC Article
Haurie C, Dale DC, Mackey MC
Blood 1998 Oct 15;92(8):2629-40. PMID: 9763544
Young GA, Iland HJ, Deveridge SF, Forrest PR, Vincent PC
Blut 1984 Mar;48(3):153-9. doi: 10.1007/BF00320338. PMID: 6697004
Evans DI, Holzel A
Proc R Soc Med 1968 Mar;61(3):302. PMID: 4171457Free PMC Article

Prognosis

Ancliff PJ, Gale RE, Linch DC
Hematology 2003 Jun;8(3):165-71. doi: 10.1080/1024533031000107497. PMID: 12745650

Clinical prediction guides

Ghizzi A, De Caro L, Costa R, Berti P
Boll Soc Ital Biol Sper 1989 Jul;65(7):617-24. PMID: 2597416
Proctor SJ, Reid MM, Low WT
Postgrad Med J 1979;55(642):279-81. doi: 10.1136/pgmj.55.642.279. PMID: 471866Free PMC Article

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