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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).
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
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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

Normal pressure hydrocephalus, or Hakim syndrome: review and update.
Tipton PW, Elder BD, Cogswell PM, Graff-Radford N
Neurol Neurochir Pol 2024;58(1):8-20. Epub 2023 Dec 6 doi: 10.5603/pjnns.97343. PMID: 38054275
Craniosynostosis: Neonatal Perspectives.
Bautista G
Neoreviews 2021 Apr;22(4):e250-e257. doi: 10.1542/neo.22-4-e250. PMID: 33795400
Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.
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
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
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

Diagnosis

How we approach hemangiomas in infants.
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
Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders.
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
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
Craniofacial syndromes.
Buchanan EP, Xue AS, Hollier LH Jr
Plast Reconstr Surg 2014 Jul;134(1):128e-153e. doi: 10.1097/PRS.0000000000000308. PMID: 25028828
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

Therapy

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
ECMO for severe ARDS: systematic review and individual patient data meta-analysis.
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
Evidences from Clinical Trials in Down Syndrome: Diet, Exercise and Body Composition.
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
Pulmonary Alveolar Proteinosis Syndrome.
Kelly A, McCarthy C
Semin Respir Crit Care Med 2020 Apr;41(2):288-298. Epub 2020 Apr 12 doi: 10.1055/s-0039-3402727. PMID: 32279299
Congenital neutropenia.
Klein C
Hematology Am Soc Hematol Educ Program 2009:344-50. doi: 10.1182/asheducation-2009.1.344. PMID: 20008220

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
Genetic bases of craniosynostoses: An update.
Armand T, Schaefer E, Di Rocco F, Edery P, Collet C, Rossi M
Neurochirurgie 2019 Nov;65(5):196-201. Epub 2019 Oct 9 doi: 10.1016/j.neuchi.2019.10.003. PMID: 31605683
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
The genetics of deafness.
Nance WE
Ment Retard Dev Disabil Res Rev 2003;9(2):109-19. doi: 10.1002/mrdd.10067. PMID: 12784229
Brown's syndrome.
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

Natural history and comorbidities of generalised and partial lipodystrophy syndromes in Spain.
Fernández-Pombo A, Sánchez-Iglesias S, Castro-Pais AI, Ginzo-Villamayor MJ, Cobelo-Gómez S, Prado-Moraña T, Díaz-López EJ, Casanueva FF, Loidi L, Araújo-Vilar D
Front Endocrinol (Lausanne) 2023;14:1250203. Epub 2023 Nov 16 doi: 10.3389/fendo.2023.1250203. PMID: 38034001Free PMC Article
Uncombable hair syndrome and beyond.
Alsabbagh MM
Acta Dermatovenerol Alp Pannonica Adriat 2022 Jun;31(2):49-64. PMID: 35751533
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
Holt-Oram syndrome.
Smith AT, Sack GH Jr, Taylor GJ
J Pediatr 1979 Oct;95(4):538-43. doi: 10.1016/s0022-3476(79)80758-1. PMID: 480027

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
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
Swaddling: a systematic review.
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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