Silver-Russell Syndrome

Genetically and clinically heterogeneous disorder characterized by low birth weight, postnatal growth retardation, facial dysmorphism, bilateral body asymmetry, and clinodactyly of the fifth fingers. Alterations in GENETIC IMPRINTING are involved. Hypomethylation of IGF2/H19 locus near an imprinting center region of chromosome 11p15 plays a role in a subset of Silver-Russell syndrome. Hypermethylation of the same chromosomal region, on the other hand, can cause BECKWITH-WIEDEMANN SYNDROME. Maternal UNIPARENTAL DISOMY for chromosome 7 is known to play a role in its etiology.

Also Known As:

Networked: 121 relevant articles (1 outcomes, 13 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Fetal Growth Retardation (Intrauterine Growth Retardation)
2.	Beckwith-Wiedemann Syndrome (Exomphalos Macroglossia Gigantism Syndrome)
3.	Precocious Puberty
4.	Prader-Willi Syndrome (Syndrome, Prader-Willi)
5.	Muscle Hypotonia (Hypotonia)

Experts

1.	Eggermann, Thomas: 12 articles (11/2020 - 09/2002)
2.	Binder, Gerhard: 8 articles (01/2022 - 09/2002)
3.	Netchine, Irène: 5 articles (01/2022 - 06/2015)
4.	Begemann, Matthias: 5 articles (07/2019 - 06/2010)
5.	Binder, G: 4 articles (10/2014 - 11/2006)
6.	Ranke, M B: 4 articles (01/2009 - 09/2006)
7.	Wollmann, Hartmut A: 4 articles (03/2008 - 09/2002)
8.	Harbison, Madeleine D: 3 articles (10/2021 - 01/2018)
9.	Ranke, Michael B: 3 articles (01/2010 - 09/2002)
10.	Eggermann, T: 3 articles (01/2008 - 09/2006)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Silver-Russell Syndrome:

1.	Growth Hormone (Somatotropin)IBA 09/01/2015 - "The purpose of this study was to assess the occlusal characteristics of individuals with growth hormone deficiency (GHD), idiopathic short stature (ISS), and Russell-Silver syndrome (RSS), and compare them to the means of a normal population. " 01/01/2010 - "The aim of this study was to determine the beneficial effects of long-term growth hormone (GH) treatment on final height (FH) in 26 children with Russell-Silver syndrome (RSS). " 09/01/1998 - "In a continuing study on the aetiology of Silver-Russell syndrome (SRS), we detected a patient with a heterozygous deletion in the growth hormone gene cluster (17q22-q24). " 10/01/1996 - "Growth hormone treatment of short children born small for gestational age or with Silver-Russell syndrome: results from KIGS (Kabi International Growth Study), including the first report on final height." 03/27/1995 - "We found significant differences in a craniometric, cephalometric, and dental study of 19 Silver-Russell syndrome patients (13 without growth hormone treatment) with appropriate controls. "
2.	SRS-AIBA 05/01/2006 - "Novel studies establish that imprinting at one of these, the IGF2-H19 domain, is epigenetically deregulated (with loss of DNA methylation) in Silver-Russell Syndrome (SRS), a congenital disease of growth retardation and asymmetry. " 10/01/2013 - "mUPD7 is the cause of approximately 5-10% of Silver-Russell syndrome (SRS), a disorder characterized by prenatal and postnatal growth retardation. " 01/01/2008 - "An opposite epimutation in the same region is associated with Silver-Russell syndrome (SRS), a growth retardation disorder characterised by a typical facial gestalt, clinodactyly V and asymmetry. " 09/01/2006 - "Recently, the opposite (epi)mutations of the same region have been reported to result in growth retardation: maternal duplications of 11p15 as well as hypomethylation of the telomeric 11p15 imprinting domain (ICR1) could be identified in patients with Silver-Russell syndrome (SRS), a disease which is in particular characterised by intrauterine and postnatal growth retardation. " 01/01/2018 - "The aim of this study is to identify novel human mutations and genes related to Silver-Russell syndrome (SRS), a syndromic form of fetal growth retardation, usually caused by epigenetic downregulation of the potent fetal growth factor IGF2.MethodsWhole-exome sequencing was carried out on members of an SRS familial case. "
3.	IGF Type 1 Receptor (IGF 1 Receptor)IBA 07/01/1997 - "Previous studies have shown that individuals with a deletion of 15q26.1-->qter, which includes the insulin-like growth factor I receptor (IGFIR) gene, may exhibit phenotypic characteristics similar to those individuals with Silver-Russell Syndrome (SRS). " 07/01/1997 - "Lack of hemizygosity for the insulin-like growth factor I receptor gene in a quantitative study of 33 Silver Russell syndrome probands and their families." 09/01/2002 - "Screening for insulin-like growth factor-I receptor mutations in patients with Silver-Russell syndrome." 03/01/2002 - "Silver-Russell syndrome is thought to result from deletion of the distal long arm of chromosome 15 on which the IGF-I receptor (IGF-IR) gene is located. " 09/01/2002 - "Individuals with a deletion of 15q26.1-->qter which contains the insulin-like growth factor-I (IGF-I) receptor gene exhibit phenotypical similarities to patients with Silver-Russell syndrome (SRS) who represent a group of short children affected by pre- and postnatal growth failure and several dysmorphic features. "
4.	Insulin-Like Growth Factor Binding ProteinsIBA 06/01/1999 - "In the present study we sought to identify genetic variation in genes for insulin-like growth factor binding proteins 1 and 3 (IGFBP1, IGFBP3) in 7p12-13 which through alteration of protein function or level of expression might contribute to the manifestation of Silver-Russell syndrome. " 01/01/2017 - "The Diagnostic Value of IGF-2 and the IGF/IGFBP-3 System in Silver-Russell Syndrome."
5.	Proteins (Proteins, Gene)FDA Link 03/01/2002 - "IGF-related proteins at birth in a case of antenatally diagnosed Silver-Russell syndrome." 06/01/1999 - "In the present study we sought to identify genetic variation in genes for insulin-like growth factor binding proteins 1 and 3 (IGFBP1, IGFBP3) in 7p12-13 which through alteration of protein function or level of expression might contribute to the manifestation of Silver-Russell syndrome. "
6.	GonadotropinsIBA 08/01/2010 - "We conclude that in a patient with a Russell-Silver syndrome-like phenotype, Sertoli cell hyperplasia was associated with somatic trisomy 8, increased aromatization, and gonadotropin-independent precocious puberty." 12/01/2017 - "Clinical studies revealed both Prader-Willi syndrome (PWS)-like marked hypotonia and Silver-Russell syndrome (SRS)-like phenotype in 50% of patients, PWS-like hypotonia alone in 20% of patients, SRS-like phenotype alone in 20% of patients, and nonsyndromic growth failure in the remaining 10% of patients in infancy, and gonadotropin-dependent precocious puberty in 76% of patients who were pubescent or older.ConclusionThese results suggest that TS14 is not only a genetically diagnosed entity but also a clinically recognizable disorder. "
7.	Untranslated RNA (Noncoding RNA)IBA 01/01/2012 - "The KCNQ1OT1 imprinting control region and non-coding RNA: new properties derived from the study of Beckwith-Wiedemann syndrome and Silver-Russell syndrome cases."
8.	SilverIBA 08/01/2018 - "We report here on the first family with short stature and Silver-Russell-like phenotype due to a microdeletion in 12q14.3. The Netchine-Harbison clinical scoring system was used for the clinical diagnosis of Silver-Russell syndrome (SRS). " 01/01/2015 - "Russell-Silver syndrome was described by Silver and Russell in the 1950s and 1960s and is characterized by body asymmetry and other growth abnormalities. " 12/01/2010 - "Submicroscopic genomic alterations in Silver-Russell syndrome and Silver-Russell-like patients." 01/01/1989 - "Five out of six of the children with Silver-Russell syndrome and seven out of 10 of the children with non-Silver-Russell IUGR gained more than 2 cm in height during 1 year of treatment with GH at a dose of 0.1 IU/kg/day. " 04/01/1977 - "The growth and development of children with the Silver-Russell syndrome have been studied (Silver, 1964; Tanner et al., 1975). "
9.	DNA (Deoxyribonucleic Acid)IBA 06/15/2015 - "Following the request for a parental project of a patient diagnosed with Silver-Russell syndrome (SRS), and the availability of both somatic and spermatozoa DNA from the proband and his father, we had the exceptional opportunity to evaluate the question of inheritance of an epimutation. " 04/01/2012 - "Almost half of the patients with Silver-Russell syndrome (SRS) are affected by DNA hypomethylation of the Imprinting Center Region 1 (ICR1) at the IGF2/H19 locus on 11p15. " 10/01/2011 - "Testing of buccal swab DNA does not increase the detection rate for imprinting control region 1 hypomethylation in Silver-Russell syndrome." 06/01/1999 - "Genomic DNA samples from 49 Silver-Russell syndrome (SRS) patients and from unaffected controls were investigated by single-strand conformation analysis. " 01/01/2023 - "Genome-wide DNA methylation analysis (GWMA) using blood leukocyte DNA was performed on 13 patients with Beckwith-Wiedemann syndrome (BWS), two patients with Silver-Russell syndrome (SRS), and four controls. "
10.	Proliferating Cell Nuclear Antigen (PCNA)IBA 01/01/2019 - "This report supports the previously reported findings of Russell-Silver syndrome (RSS) like phenotype caused by this unusual mechanism (CDKN1C mutations in the PCNA domain), highlights subtle radiological features not described previously and the phenotypic variability between two affected siblings. " 01/01/2019 - "Familial Russell-Silver Syndrome like Phenotype in the PCNA Domain of the CDKN1C Gene, a Further Case." 12/01/2013 - "CDKN1C mutation affecting the PCNA-binding domain as a cause of familial Russell Silver syndrome." 03/01/2017 - "Recently, gain-of-function mutations in the PCNA domain of CDKN1C have been reported as the genetic basis of various growth-retarded syndromes including IMAGe syndrome, Russell Silver syndrome as well as a novel undergrowth syndrome that additionally exhibited early adulthood onset diabetes. " 01/01/2016 - "Recently, gain-of-function mutations within the PCNA domain have been described in two disorders characterized by growth failure, namely IMAGe (intra-uterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenita and genital abnormalities) syndrome and Silver-Russell syndrome (SRS). "

Therapies and Procedures

1.	Therapeutics 10/01/1996 - "We have demonstrated significant improvement in growth in Silver Russell syndrome after 3 years of GH therapy, however data on estimated mature height and final height are insufficient to conclude final outcomes. " 01/01/2011 - "Possible future uses for GH therapy could include the treatment of syndromes such as Russell-Silver syndrome or chondrodystrophy. " 12/01/1995 - "Normative data on spontaneous growth of children with Silver-Russell syndrome are described, allowing a better counselling of patients as well as the judgement of the effects of growth promoting therapies." 01/01/2009 - "Silver-Russell syndrome, congenital heart defects, infections of mothers or smoking during pregnancy, explain the variation in the first-year growth response to GH therapy. " 10/01/1996 - "The response to growth hormone (GH) therapy was studied in children born small for gestational age (SGA; n = 593) and in those with Silver-Russell syndrome (SRS; n = 127) using data from KIGS (Kabi International Growth Study). "
2.	Ligation 05/01/2015 - "Multiplex ligation-dependent probe amplification analysis showed a normal methylation pattern and normal dosage at 11p15.5. A PubMed search for all peer-reviewed publications (original articles and reviews) using the key words Silver-Russell syndrome, Mayer-Rokitansky-Küster-Hauser syndrome, genetics, hypomethylation and reproductive anomalies identified three cases of SRS with MRKH, two of which were associated with significant hypomethylation of the H19 imprinting control region of the 11p15.5 locus. " 03/01/2008 - "Search for subtelomeric imbalances by multiplex ligation-dependent probe amplification in Silver-Russell syndrome." 01/01/2008 - "Use of multiplex ligation-dependent probe amplification increases the detection rate for 11p15 epigenetic alterations in Silver-Russell syndrome." 09/01/2013 - "Methylation-specific (MS) multiplex ligation-dependent probe amplification (MLPA) at two differentially methylated regions (DMRs) at chromosome 11p15, H19-DMR and LIT1-DMR, and microsatellite analysis for uniparental disomy (UPD) at chromosome 7 or 11, have been recommended for the genetic diagnosis of the Beckwith-Wiedemann syndrome (BWS) and the Silver-Russell syndrome (SRS). "
3.	Bariatric Surgery 01/01/2017 - "Metabolic signatures in an adolescent with Silver-Russell syndrome and outcomes after bariatric surgery."
4.	Deep Brain Stimulation 01/01/2023 - "Deep Brain Stimulation for an Unusual Presentation of Myoclonus Dystonia Associated with Russell-Silver Syndrome."
5.	Distraction Osteogenesis 07/01/1999 - "Distraction osteogenesis in Silver Russell syndrome to expand the mandible." 07/01/1999 - "In this report, a patient with Silver Russell syndrome and severe mandibular hypoplasia was treated by means of distraction osteogenesis of the midsymphysis to widen the mandible in concert with sagittal-ramus osteotomies to lengthen the mandible. "