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Congenital neutropenia-myelofibrosis-nephromegaly syndrome(SCN5)

MedGen UID:
815361
Concept ID:
C3809031
Disease or Syndrome
Synonym: Severe congenital neutropenia 5, autosomal recessive
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): VPS45 (1q21.2)
 
Monarch Initiative: MONDO:0014118
OMIM®: 615285
Orphanet: ORPHA369852

Definition

Severe congenital neutropenia-5 is an autosomal recessive primary immunodeficiency disorder characterized primarily by neutropenia and neutrophil dysfunction, a lack of response to G-CSF, life-threatening infections, bone marrow fibrosis, and renal extramedullary hematopoiesis (summary by Vilboux et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of severe congenital neutropenia, see SCN1 (202700). [from OMIM]

Clinical features

From HPO
Enlarged kidney
MedGen UID:
108156
Concept ID:
C0542518
Finding
An abnormal increase in the size of the kidney.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Chronic diarrhea
MedGen UID:
96036
Concept ID:
C0401151
Finding
The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Extramedullary hematopoiesis
MedGen UID:
392862
Concept ID:
C2613439
Disease or Syndrome
The process of hematopoiesis occurring outside of the bone marrow (in the liver, thymus, and spleen) in the postnatal organisms.
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Increased circulating antibody concentration
MedGen UID:
1713383
Concept ID:
C5397581
Finding
An increased level of gamma globulin (immunoglobulin) in the blood.

Professional guidelines

PubMed

Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, Raivio T, Pitteloud N
Endocr Rev 2019 Apr 1;40(2):669-710. doi: 10.1210/er.2018-00116. PMID: 30698671
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
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Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, Church DM, Crolla JA, Eichler EE, Epstein CJ, Faucett WA, Feuk L, Friedman JM, Hamosh A, Jackson L, Kaminsky EB, Kok K, Krantz ID, Kuhn RM, Lee C, Ostell JM, Rosenberg C, Scherer SW, Spinner NB, Stavropoulos DJ, Tepperberg JH, Thorland EC, Vermeesch JR, Waggoner DJ, Watson MS, Martin CL, Ledbetter DH
Am J Hum Genet 2010 May 14;86(5):749-64. doi: 10.1016/j.ajhg.2010.04.006. PMID: 20466091Free PMC Article

Recent clinical studies

Etiology

Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Jacquinet A, Millar D, Lehman A
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Diagnosis

Chen J, Kanekar S
Clin Perinatol 2022 Sep;49(3):771-790. Epub 2022 Aug 22 doi: 10.1016/j.clp.2022.04.005. PMID: 36113934
Mayer JLR, Intzes S, Oza VS, Blei F
Pediatr Blood Cancer 2022 Aug;69 Suppl 3:e29077. Epub 2021 Jun 20 doi: 10.1002/pbc.29077. PMID: 34151510
Karol LA
J Pediatr Orthop 2019 Jul;39(Issue 6, Supplement 1 Suppl 1):S38-S43. doi: 10.1097/BPO.0000000000001351. PMID: 31169646
Jacquinet A, Millar D, Lehman A
Am J Med Genet A 2016 Aug;170(8):2141-72. Epub 2016 Jun 8 doi: 10.1002/ajmg.a.37775. PMID: 27273803
Buchanan EP, Xue AS, Hollier LH Jr
Plast Reconstr Surg 2014 Jul;134(1):128e-153e. doi: 10.1097/PRS.0000000000000308. PMID: 25028828

Therapy

Lees CC, Romero R, Stampalija T, Dall'Asta A, DeVore GA, Prefumo F, Frusca T, Visser GHA, Hobbins JC, Baschat AA, Bilardo CM, Galan HL, Campbell S, Maulik D, Figueras F, Lee W, Unterscheider J, Valensise H, Da Silva Costa F, Salomon LJ, Poon LC, Ferrazzi E, Mari G, Rizzo G, Kingdom JC, Kiserud T, Hecher K
Am J Obstet Gynecol 2022 Mar;226(3):366-378. Epub 2022 Jan 10 doi: 10.1016/j.ajog.2021.11.1357. PMID: 35026129Free PMC Article
Ceccarini G, Magno S, Gilio D, Pelosini C, Santini F
Presse Med 2021 Nov;50(3):104073. Epub 2021 Sep 20 doi: 10.1016/j.lpm.2021.104073. PMID: 34547374
Karol LA
J Pediatr Orthop 2019 Jul;39(Issue 6, Supplement 1 Suppl 1):S38-S43. doi: 10.1097/BPO.0000000000001351. PMID: 31169646
Joazlina ZY, Wastie ML, Kamarulzaman A
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Prognosis

Karol LA
J Pediatr Orthop 2019 Jul;39(Issue 6, Supplement 1 Suppl 1):S38-S43. doi: 10.1097/BPO.0000000000001351. PMID: 31169646
Ahn KH, Park YJ, Hong SC, Lee EH, Lee JS, Oh MJ, Kim HJ
J Obstet Gynaecol 2016 Jul;36(5):563-6. Epub 2016 Mar 10 doi: 10.3109/01443615.2015.1127905. PMID: 26965725
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J Craniofac Surg 2009 Jan;20(1):254-6. doi: 10.1097/SCS.0b013e318184357a. PMID: 19165041
Nance WE
Ment Retard Dev Disabil Res Rev 2003;9(2):109-19. doi: 10.1002/mrdd.10067. PMID: 12784229
D'Alton ME, Simpson LL
Semin Perinatol 1995 Oct;19(5):375-86. doi: 10.1016/s0146-0005(05)80015-1. PMID: 8821025

Clinical prediction guides

Rosenfeld E, Ganguly A, De Leon DD
Am J Med Genet C Semin Med Genet 2019 Dec;181(4):682-692. Epub 2019 Aug 14 doi: 10.1002/ajmg.c.31737. PMID: 31414570Free PMC Article
Jacquinet A, Millar D, Lehman A
Am J Med Genet A 2016 Aug;170(8):2141-72. Epub 2016 Jun 8 doi: 10.1002/ajmg.a.37775. PMID: 27273803
Kellermayer R
Genet Med 2006 Apr;8(4):213-6. doi: 10.1097/01.gim.0000214457.58378.1a. PMID: 16617241
Rosser T
Arch Neurol 2003 Oct;60(10):1471-3. doi: 10.1001/archneur.60.10.1471. PMID: 14568821
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Recent systematic reviews

Boot E, Óskarsdóttir S, Loo JCY, Crowley TB, Orchanian-Cheff A, Andrade DM, Arganbright JM, Castelein RM, Cserti-Gazdewich C, de Reuver S, Fiksinski AM, Klingberg G, Lang AE, Mascarenhas MR, Moss EM, Nowakowska BA, Oechslin E, Palmer L, Repetto GM, Reyes NGD, Schneider M, Silversides C, Sullivan KE, Swillen A, van Amelsvoort TAMJ, Van Batavia JP, Vingerhoets C, McDonald-McGinn DM, Bassett AS
Genet Med 2023 Mar;25(3):100344. Epub 2023 Feb 2 doi: 10.1016/j.gim.2022.11.012. PMID: 36729052
Malaza N, Masete M, Adam S, Dias S, Nyawo T, Pheiffer C
Int J Environ Res Public Health 2022 Aug 31;19(17) doi: 10.3390/ijerph191710846. PMID: 36078559Free PMC Article
Martín-Martín M, Cortés-Martín J, Tovar-Gálvez MI, Sánchez-García JC, Díaz-Rodríguez L, Rodríguez-Blanque R
Int J Environ Res Public Health 2022 Feb 7;19(3) doi: 10.3390/ijerph19031870. PMID: 35162892Free PMC Article
Adler A, Novelli V, Amin AS, Abiusi E, Care M, Nannenberg EA, Feilotter H, Amenta S, Mazza D, Bikker H, Sturm AC, Garcia J, Ackerman MJ, Hershberger RE, Perez MV, Zareba W, Ware JS, Wilde AAM, Gollob MH
Circulation 2020 Feb 11;141(6):418-428. Epub 2020 Jan 27 doi: 10.1161/CIRCULATIONAHA.119.043132. PMID: 31983240Free PMC Article
Gravholt CH, Andersen NH, Conway GS, Dekkers OM, Geffner ME, Klein KO, Lin AE, Mauras N, Quigley CA, Rubin K, Sandberg DE, Sas TCJ, Silberbach M, Söderström-Anttila V, Stochholm K, van Alfen-van derVelden JA, Woelfle J, Backeljauw PF; International Turner Syndrome Consensus Group
Eur J Endocrinol 2017 Sep;177(3):G1-G70. doi: 10.1530/EJE-17-0430. PMID: 28705803

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