Details of Disease

Disease Name

Silver-Russell syndrome

Silver Russell dwarfism; Russell-Silver Syndrome; SRS; Silver-Russell syndrome; Russell-Silver dwarfism; Silver-Russell dwarfism; Silver Russell syndrome; Russell Silver syndrome; Russell-Silver syndrome

Definition

Silver-Russell syndrome is characterized by growth retardation with antenatal onset, characteristic facies and limb asymmetry.

Disease Hierarchy

DIS7667R: Multiple congenital anomalies/dysmorphic syndrome-variable intellectual disability syndrome

DIS6SVEE: Syndromic disease

DISYKSRF: Genetic disease

DISM5BB5: Chromosomal disorder

DISSVJ1D: Silver-Russell syndrome

Disease Identifiers

MONDO ID

MONDO_0008394

MESH ID

D056730

UMLS CUI

C0175693

MedGen ID

104492

Orphanet ID

813

SNOMED CT ID

15069006

General Information of Disease (ID: DISSVJ1D)

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDKN1C	TTBSUAR	Limited	Autosomal dominant	[1]
GART	TTEXB9Z	Limited	Genetic Variation	[2]
IGFBP1	TTCJTWF	Limited	Genetic Variation	[3]
IGFBP3	TTZHNQA	Limited	Biomarker	[4]
CTCFL	TTY0RZT	Strong	Genetic Variation	[5]
GH1	TTT3YKH	Strong	Biomarker	[6]
IGF2	TTE8WGO	Strong	Altered Expression	[7]
KCNQ1	TT846HF	Strong	Biomarker	[8]
NSD1	TTTSJ3H	Strong	Biomarker	[9]
PTPN11	TT7WUAV	Strong	Biomarker	[10]
RAF1	TTAN5W2	Strong	Biomarker	[11]
TGM1	TT7A949	Strong	Genetic Variation	[12]
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⏷ Show the Full List of 12 DTT(s)

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CPA4	DEXKD7J	Strong	Altered Expression	[13]
GLDC	DEIN8FB	Strong	Genetic Variation	[14]
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This Disease Is Related to 29 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CDKN1C	OTASTJ3Q	Limited	Autosomal dominant	[1]
GARS1	OT5B6R9Y	Limited	Biomarker	[2]
KCNIP1	OTGLGK1R	Limited	Biomarker	[15]
MAD2L1BP	OT2O2IUJ	Limited	Biomarker	[2]
SPAST	OTIF3AJI	Limited	Biomarker	[16]
AMT	OTQYEWZQ	Strong	Genetic Variation	[14]
BSCL2	OT73V6Y4	Strong	Biomarker	[17]
CCDC22	OT1A1ZXH	Strong	Genetic Variation	[18]
COPG2	OT1DFC8W	Strong	Biomarker	[19]
CSH1	OT33HTRR	Strong	Biomarker	[20]
CTCF	OT8ZB70U	Strong	Biomarker	[21]
FOXP2	OTVX6A59	Strong	Biomarker	[22]
GCSH	OTNC1OKA	Strong	Genetic Variation	[14]
GH2	OT32TR4C	Strong	Biomarker	[20]
HOXA4	OTNVTQDT	Strong	Posttranslational Modification	[23]
KCNE1	OTZNQUW9	Strong	Genetic Variation	[24]
KPNA2	OTU7FOE6	Strong	Genetic Variation	[25]
LZTR1	OTIDM6XO	Strong	Biomarker	[26]
MBD3	OTRL76H5	Strong	Genetic Variation	[27]
OBSL1	OT6M8M3J	Strong	Genetic Variation	[28]
OSBPL5	OTI1UJXT	Strong	Biomarker	[29]
PEG10	OTWD2278	Strong	Biomarker	[14]
PHLDA2	OTMV9DPP	Strong	Biomarker	[8]
PLAG1	OTT9AJQY	Strong	Biomarker	[30]
PLAGL1	OTZAO900	Strong	Biomarker	[14]
RIT1	OTVNOGOH	Strong	Biomarker	[31]
SGCE	OT9F17JB	Strong	Biomarker	[32]
SMS	OT8JYKNH	Strong	Genetic Variation	[33]
SOS1	OTTCWXC3	Strong	Biomarker	[34]
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⏷ Show the Full List of 29 DOT(s)

References

1	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2	Further evidence for genetic heterogeneity of distal HMN type V, CMT2 with predominant hand involvement and Silver syndrome.J Neurol Sci. 2007 Dec 15;263(1-2):100-6. doi: 10.1016/j.jns.2007.06.047. Epub 2007 Jul 30.
3	Biparental expression of IGFBP1 and IGFBP3 renders their involvement in the etiology of Silver-Russell syndrome unlikely.Ann Genet. 1999;42(2):117-21.
4	The Diagnostic Value of IGF-2 and the IGF/IGFBP-3 System in Silver-Russell Syndrome.Horm Res Paediatr. 2017;88(3-4):201-207. doi: 10.1159/000477666. Epub 2017 Jul 4.
5	No evidence for mutations of CTCFL/BORIS in Silver-Russell syndrome patients with IGF2/H19 imprinting control region 1 hypomethylation.PLoS One. 2009 Aug 13;4(8):e6631. doi: 10.1371/journal.pone.0006631.
6	Effect of Cyproheptadine on Weight and Growth Velocity in Children With Silver-Russell Syndrome.J Pediatr Gastroenterol Nutr. 2018 Feb;66(2):306-311. doi: 10.1097/MPG.0000000000001708.
7	IGF2 Mutations.J Clin Endocrinol Metab. 2020 Jan 1;105(1):dgz034. doi: 10.1210/clinem/dgz034.
8	Behavioural abnormalities in a novel mouse model for Silver Russell Syndrome.Hum Mol Genet. 2016 Dec 15;25(24):5407-5417. doi: 10.1093/hmg/ddw357.
9	NSD1 duplication in Silver-Russell syndrome (SRS): molecular karyotyping in patients with SRS features.Clin Genet. 2017 Jan;91(1):73-78. doi: 10.1111/cge.12803. Epub 2016 Jun 30.
10	Mouse model of Noonan syndrome reveals cell type- and gene dosage-dependent effects of Ptpn11 mutation.Nat Med. 2004 Aug;10(8):849-57. doi: 10.1038/nm1084. Epub 2004 Jul 25.
11	Increased BRAF heterodimerization is the common pathogenic mechanism for noonan syndrome-associated RAF1 mutants.Mol Cell Biol. 2012 Oct;32(19):3872-90. doi: 10.1128/MCB.00751-12. Epub 2012 Jul 23.
12	Mild Beckwith-Wiedemann and severe long-QT syndrome due to deletion of the imprinting center 2 on chromosome 11p.Eur J Hum Genet. 2013 Sep;21(9):965-9. doi: 10.1038/ejhg.2012.280. Epub 2013 Mar 20.
13	The imprinted region on human chromosome 7q32 extends to the carboxypeptidase A gene cluster: an imprinted candidate for Silver-Russell syndrome.J Med Genet. 2003 Apr;40(4):249-56. doi: 10.1136/jmg.40.4.249.
14	Methylation profiling in individuals with Russell-Silver syndrome.Am J Med Genet A. 2010 Feb;152A(2):347-55. doi: 10.1002/ajmg.a.33204.
15	Saikosaponin A modulates remodeling of Kv4.2-mediated A-type voltage-gated potassium currents in rat chronic temporal lobe epilepsy.Drug Des Devel Ther. 2018 Sep 11;12:2945-2958. doi: 10.2147/DDDT.S166408. eCollection 2018.
16	Silver syndrome variant of hereditary spastic paraplegia: A locus to 4p and allelism with SPG4.Neurology. 2008 May 20;70(21):1959-66. doi: 10.1212/01.wnl.0000294330.27058.61. Epub 2008 Apr 9.
17	ALS and MMN mimics in patients with BSCL2 mutations: the expanding clinical spectrum of SPG17 hereditary spastic paraplegia.J Neurol. 2017 Jan;264(1):11-20. doi: 10.1007/s00415-016-8301-2. Epub 2016 Oct 13.
18	Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome. Eur J Hum Genet. 2015 May;23(5):633-8. doi: 10.1038/ejhg.2014.109. Epub 2014 Jun 11.
19	gamma2-COP, a novel imprinted gene on chromosome 7q32, defines a new imprinting cluster in the human genome.Hum Mol Genet. 1999 Dec;8(13):2387-96. doi: 10.1093/hmg/8.13.2387.
20	Characterization of genomic variants in CSH1 and GH2, two candidate genes for Silver-Russell syndrome in 17q24-q25.Genet Test. 2003 Fall;7(3):259-63. doi: 10.1089/109065703322537304.
21	Disruption of genomic neighbourhood at the imprinted IGF2-H19 locus in Beckwith-Wiedemann syndrome and Silver-Russell syndrome.Hum Mol Genet. 2011 Apr 1;20(7):1363-74. doi: 10.1093/hmg/ddr018. Epub 2011 Jan 31.
22	Absence of a paternally inherited FOXP2 gene in developmental verbal dyspraxia.Am J Hum Genet. 2006 Nov;79(5):965-72. doi: 10.1086/508902. Epub 2006 Sep 27.
23	Hypomethylation of HOXA4 promoter is common in Silver-Russell syndrome and growth restriction and associates with stature in healthy children.Sci Rep. 2017 Nov 16;7(1):15693. doi: 10.1038/s41598-017-16070-5.
24	Identification of a 21q22 duplication in a Silver-Russell syndrome patient further narrows down the Down syndrome critical region.Am J Med Genet A. 2010 Feb;152A(2):356-9. doi: 10.1002/ajmg.a.33217.
25	Genomic structure of karyopherin alpha2 ( KPNA2) within a low-copy repeat on chromosome 17q23-q24 and mutation analysis in patients with Russell-Silver syndrome.Hum Genet. 2001 Nov;109(5):479-86. doi: 10.1007/s004390100605. Epub 2001 Oct 3.
26	Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination.Science. 2018 Dec 7;362(6419):1177-1182. doi: 10.1126/science.aap7607. Epub 2018 Nov 15.
27	MBD3 mutations are not responsible for ICR1 hypomethylation in Silver-Russell syndrome.Eur J Med Genet. 2010 Jan-Feb;53(1):23-4. doi: 10.1016/j.ejmg.2009.12.002. Epub 2009 Dec 16.
28	Genetic characterisation of a cohort of children clinically labelled as GH or IGF1 insensitive: diagnostic value of serum IGF1 and height at presentation.Eur J Endocrinol. 2015 Feb;172(2):151-61. doi: 10.1530/EJE-14-0541. Epub 2014 Nov 19.
29	Genome-wide analysis of differential DNA methylation in Silver-Russell syndrome.Sci China Life Sci. 2017 Jul;60(7):692-699. doi: 10.1007/s11427-017-9079-7. Epub 2017 Jun 14.
30	Genetic disruption of the oncogenic HMGA2-PLAG1-IGF2 pathway causes fetal growth restriction.Genet Med. 2018 Feb;20(2):250-258. doi: 10.1038/gim.2017.105. Epub 2017 Aug 10.
31	New Noonan syndrome model mice with RIT1 mutation exhibit cardiac hypertrophy and susceptibility to -adrenergic stimulation-induced cardiac fibrosis.EBioMedicine. 2019 Apr;42:43-53. doi: 10.1016/j.ebiom.2019.03.014. Epub 2019 Mar 18.
32	Quantitative analysis of methylation status at 11p15 and 7q21 for the genetic diagnosis of Beckwith-Wiedemann syndrome and Silver-Russell syndrome.J Hum Genet. 2013 Sep;58(9):604-10. doi: 10.1038/jhg.2013.67. Epub 2013 Jun 27.
33	Silver Russel syndrome in an aboriginal patient from Australia.Am J Med Genet A. 2018 Dec;176(12):2561-2563. doi: 10.1002/ajmg.a.40502. Epub 2018 Aug 27.
34	Activation of multiple signaling pathways causes developmental defects in mice with a Noonan syndromeassociated Sos1 mutation.J Clin Invest. 2010 Dec;120(12):4353-65. doi: 10.1172/JCI43910.