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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 level
MedGen UID:
1713383
Concept ID:
C5397581
Finding
An increased level of gamma globulin (immunoglobulin) in the blood.

Professional guidelines

PubMed

Franchi-Abella S, Gonzales E, Ackermann O, Branchereau S, Pariente D, Guérin F; International Registry of Congenital Portosystemic Shunt members
Abdom Radiol (NY) 2018 Aug;43(8):2023-2036. doi: 10.1007/s00261-018-1619-8. PMID: 29730740
Engel AG, Shen XM, Selcen D, Sine SM
Lancet Neurol 2015 Apr;14(4):420-34. doi: 10.1016/S1474-4422(14)70201-7. PMID: 25792100Free PMC Article
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

Butel-Simoes GI, Jones P, Wood EM, Spelman D, Woolley IJ, Ojaimi S
Ann Hematol 2022 Jul;101(7):1421-1434. Epub 2022 Apr 22 doi: 10.1007/s00277-022-04765-3. PMID: 35451619
Aref-Eshghi E, Kerkhof J, Pedro VP; Groupe DI France, Barat-Houari M, Ruiz-Pallares N, Andrau JC, Lacombe D, Van-Gils J, Fergelot P, Dubourg C, Cormier-Daire V, Rondeau S, Lecoquierre F, Saugier-Veber P, Nicolas G, Lesca G, Chatron N, Sanlaville D, Vitobello A, Faivre L, Thauvin-Robinet C, Laumonnier F, Raynaud M, Alders M, Mannens M, Henneman P, Hennekam RC, Velasco G, Francastel C, Ulveling D, Ciolfi A, Pizzi S, Tartaglia M, Heide S, Héron D, Mignot C, Keren B, Whalen S, Afenjar A, Bienvenu T, Campeau PM, Rousseau J, Levy MA, Brick L, Kozenko M, Balci TB, Siu VM, Stuart A, Kadour M, Masters J, Takano K, Kleefstra T, de Leeuw N, Field M, Shaw M, Gecz J, Ainsworth PJ, Lin H, Rodenhiser DI, Friez MJ, Tedder M, Lee JA, DuPont BR, Stevenson RE, Skinner SA, Schwartz CE, Genevieve D, Sadikovic B
Am J Hum Genet 2020 Mar 5;106(3):356-370. Epub 2020 Feb 27 doi: 10.1016/j.ajhg.2020.01.019. PMID: 32109418Free PMC Article
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
Cereda A, Carey JC
Orphanet J Rare Dis 2012 Oct 23;7:81. doi: 10.1186/1750-1172-7-81. PMID: 23088440Free PMC Article
Wilson ME, Eustis HS Jr, Parks MM
Surv Ophthalmol 1989 Nov-Dec;34(3):153-72. doi: 10.1016/0039-6257(89)90100-8. PMID: 2694414

Diagnosis

Ho ML
Neuroimaging Clin N Am 2023 Aug;33(3):375-388. Epub 2023 Jun 1 doi: 10.1016/j.nic.2023.04.002. PMID: 37356857
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
Kirkorian AY, Grossberg AL, Püttgen KB
Semin Cutan Med Surg 2016 Sep;35(3):128-36. doi: 10.12788/j.sder.2016.051. PMID: 27607321
Buchanan EP, Xue AS, Hollier LH Jr
Plast Reconstr Surg 2014 Jul;134(1):128e-153e. doi: 10.1097/PRS.0000000000000308. PMID: 25028828
Cereda A, Carey JC
Orphanet J Rare Dis 2012 Oct 23;7:81. doi: 10.1186/1750-1172-7-81. PMID: 23088440Free PMC Article

Therapy

Rosa J
Vnitr Lek 2023 Summer;69(4):254-260. doi: 10.36290/vnl.2023.048. PMID: 37468295
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
Combes A, Peek GJ, Hajage D, Hardy P, Abrams D, Schmidt M, Dechartres A, Elbourne D
Intensive Care Med 2020 Nov;46(11):2048-2057. Epub 2020 Oct 6 doi: 10.1007/s00134-020-06248-3. PMID: 33021684Free PMC Article
Martínez-Espinosa RM, Molina Vila MD, Reig García-Galbis M
Int J Environ Res Public Health 2020 Jun 16;17(12) doi: 10.3390/ijerph17124294. PMID: 32560141Free PMC Article
Blake KD, Prasad C
Orphanet J Rare Dis 2006 Sep 7;1:34. doi: 10.1186/1750-1172-1-34. PMID: 16959034Free PMC Article

Prognosis

Calcagni G, Unolt M, Digilio MC, Baban A, Versacci P, Tartaglia M, Baldini A, Marino B
Expert Rev Mol Diagn 2017 Sep;17(9):861-870. Epub 2017 Aug 3 doi: 10.1080/14737159.2017.1360766. PMID: 28745539
Cereda A, Carey JC
Orphanet J Rare Dis 2012 Oct 23;7:81. doi: 10.1186/1750-1172-7-81. PMID: 23088440Free PMC Article
Hidestrand P, Vasconez H, Cottrill C
J Craniofac Surg 2009 Jan;20(1):254-6. doi: 10.1097/SCS.0b013e318184357a. PMID: 19165041
D'Alton ME, Simpson LL
Semin Perinatol 1995 Oct;19(5):375-86. doi: 10.1016/s0146-0005(05)80015-1. PMID: 8821025
Wilson ME, Eustis HS Jr, Parks MM
Surv Ophthalmol 1989 Nov-Dec;34(3):153-72. doi: 10.1016/0039-6257(89)90100-8. PMID: 2694414

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
Ventura CV, Ventura Filho MC, Ventura LO
Top Magn Reson Imaging 2019 Feb;28(1):23-27. doi: 10.1097/RMR.0000000000000192. PMID: 30817677
Vajravelu ME, De León DD
Curr Opin Pediatr 2018 Aug;30(4):568-575. doi: 10.1097/MOP.0000000000000645. PMID: 29750770Free PMC Article
Agaimy A, Foulkes WD
Semin Diagn Pathol 2018 May;35(3):193-198. Epub 2018 Feb 1 doi: 10.1053/j.semdp.2018.01.002. PMID: 29397238
Vogel F Jr
Clin Podiatry 1984 Dec;1(3):581-99. PMID: 6536410

Recent systematic reviews

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
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
Finsterer J
Orphanet J Rare Dis 2019 Feb 26;14(1):57. doi: 10.1186/s13023-019-1025-5. PMID: 30808424Free 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
van Sleuwen BE, Engelberts AC, Boere-Boonekamp MM, Kuis W, Schulpen TW, L'Hoir MP
Pediatrics 2007 Oct;120(4):e1097-106. doi: 10.1542/peds.2006-2083. PMID: 17908730

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