U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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).
Autosomal recessive inheritance (Orphanet)
 
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.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Hepatomegaly
MedGen UID:
42428
•Concept ID:
C0019209
•
Finding
Abnormally increased size of the liver.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Anemia
MedGen UID:
1526
•Concept ID:
C0002871
•
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
See: Feature record | Search on this feature
Thrombocytopenia
MedGen UID:
52737
•Concept ID:
C0040034
•
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Leukopenia
MedGen UID:
6073
•Concept ID:
C0023530
•
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
See: Feature record | Search on this feature
Splenomegaly
MedGen UID:
52469
•Concept ID:
C0038002
•
Finding
Abnormal increased size of the spleen.
See: Feature record | Search on this feature
Recurrent infections
MedGen UID:
65998
•Concept ID:
C0239998
•
Finding
Increased susceptibility to infections.
See: Feature record | Search on this feature
Neutropenia
MedGen UID:
163121
•Concept ID:
C0853697
•
Finding
An abnormally low number of neutrophils in the peripheral blood.
See: Feature record | Search on this feature
Increased circulating antibody concentration
MedGen UID:
1713383
•Concept ID:
C5397581
•
Finding
An increased level of gamma globulin (immunoglobulin) in the blood.
See: Feature record | Search on this feature
Show allHide all

Professional guidelines

PubMed

Clinical Management of Congenital Hypogonadotropic Hypogonadism.
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
ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.
Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW; American College of Gastroenterology
Am J Gastroenterol 2015 Feb;110(2):223-62; quiz 263. Epub 2015 Feb 3 doi: 10.1038/ajg.2014.435. PMID: 25645574Free PMC Article
Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies.
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

Congenital hyperinsulinism disorders: Genetic and clinical characteristics.
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
Etiologies of uterine malformations.
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
Syncope in Hereditary Arrhythmogenic Syndromes.
Adler A, Viskin S
Cardiol Clin 2015 Aug;33(3):433-40. doi: 10.1016/j.ccl.2015.04.011. PMID: 26115829
The trisomy 18 syndrome.
Cereda A, Carey JC
Orphanet J Rare Dis 2012 Oct 23;7:81. doi: 10.1186/1750-1172-7-81. PMID: 23088440Free PMC Article
Congenital myasthenic syndromes.
Beeson D, Palace J, Vincent A
Curr Opin Neurol 1997 Oct;10(5):402-7. doi: 10.1097/00019052-199710000-00008. PMID: 9330886

Diagnosis

Etiologies of uterine malformations.
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
Syncope in Hereditary Arrhythmogenic Syndromes.
Adler A, Viskin S
Cardiol Clin 2015 Aug;33(3):433-40. doi: 10.1016/j.ccl.2015.04.011. PMID: 26115829
The trisomy 18 syndrome.
Cereda A, Carey JC
Orphanet J Rare Dis 2012 Oct 23;7:81. doi: 10.1186/1750-1172-7-81. PMID: 23088440Free PMC Article
Commonest overgrowth syndromes.
Ekmektzoglou K, Demestiha T, Troupis G, Xanthos T
Fetal Pediatr Pathol 2012 Apr;31(2):94-111. doi: 10.3109/15513815.2011.650293. PMID: 22409408
Congenital myasthenic syndromes.
Beeson D, Palace J, Vincent A
Curr Opin Neurol 1997 Oct;10(5):402-7. doi: 10.1097/00019052-199710000-00008. PMID: 9330886

Therapy

17q12 microdeletion syndrome.
Bhargav VSLV, Venkatachari M, Arun Babu T
BMJ Case Rep 2024 Nov 7;17(11) doi: 10.1136/bcr-2024-262697. PMID: 39510608
Clinical Opinion: The diagnosis and management of suspected fetal growth restriction: an evidence-based approach.
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
An Introduction to Epigenetics.
Barbara MA, Abdilla Y, Calleja-Agius J
Neonatal Netw 2017 May 1;36(3):124-128. doi: 10.1891/0730-0832.36.3.124. PMID: 28494823
Congenital neutropenia.
Townshend J, Clark J, Cant A, Carey P, Kumar P, Campbell D
Arch Dis Child Educ Pract Ed 2008 Feb;93(1):14-8. doi: 10.1136/adc.2006.109264. PMID: 18208980
VACTERL-H syndrome.
Herman TE, Siegel MJ
J Perinatol 2002 Sep;22(6):496-8. doi: 10.1038/sj.jp.7210765. PMID: 12168129

Prognosis

Mitochondrial DNA Depletion Syndromes.
Basel D
Clin Perinatol 2020 Mar;47(1):123-141. Epub 2019 Oct 31 doi: 10.1016/j.clp.2019.10.008. PMID: 32000920
Evaluation and management of syndromic congenital hearing loss.
Casazza G, Meier JD
Curr Opin Otolaryngol Head Neck Surg 2017 Oct;25(5):378-384. doi: 10.1097/MOO.0000000000000397. PMID: 28697000
Congenital varicella syndrome: A systematic review.
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
The trisomy 18 syndrome.
Cereda A, Carey JC
Orphanet J Rare Dis 2012 Oct 23;7:81. doi: 10.1186/1750-1172-7-81. PMID: 23088440Free PMC Article
Yunis-Varon syndrome.
Bhatia S, Holla RG
Indian Pediatr 2005 Apr;42(4):373-5. PMID: 15876600

Clinical prediction guides

Genetics of congenital arrhythmia syndromes: the challenge of variant interpretation.
Glazer AM
Curr Opin Genet Dev 2022 Dec;77:102004. Epub 2022 Nov 9 doi: 10.1016/j.gde.2022.102004. PMID: 36368182Free PMC Article
Congenital hyperinsulinism disorders: Genetic and clinical characteristics.
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
Etiologies of uterine malformations.
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
The versatile RECQL4.
Kellermayer R
Genet Med 2006 Apr;8(4):213-6. doi: 10.1097/01.gim.0000214457.58378.1a. PMID: 16617241
Congenital glenoid dysplasia.
Currarino G, Sheffield E, Twickler D
Pediatr Radiol 1998 Jan;28(1):30-7. doi: 10.1007/s002470050287. PMID: 9426270

Recent systematic reviews

A Systematic Review to Compare Adverse Pregnancy Outcomes in Women with Pregestational Diabetes and Gestational Diabetes.
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
CONGENITAL LONG QT SYNDROME: A SYSTEMATIC REVIEW.
Galić E, Bešlić P, Kilić P, Planinić Z, Pašalić A, Galić I, Ćubela VV, Pekić P
Acta Clin Croat 2021 Dec;60(4):739-748. doi: 10.20471/acc.2021.60.04.22. PMID: 35734489Free PMC Article
Congenital Zika syndrome: A systematic review.
Freitas DA, Souza-Santos R, Carvalho LMA, Barros WB, Neves LM, Brasil P, Wakimoto MD
PLoS One 2020;15(12):e0242367. Epub 2020 Dec 15 doi: 10.1371/journal.pone.0242367. PMID: 33320867Free PMC Article
An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome.
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
Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting.
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

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...