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Silver-Russell syndrome 1(SRS1)

MedGen UID:
1718472
Concept ID:
C5393125
Disease or Syndrome
Synonyms: Chromosome 7-Related Russell-Silver Syndrome; SRS1
 
Genes (locations): H19-ICR (11p15.5); IGF2 (11p15.5)
 
Monarch Initiative: MONDO:0020796
OMIM®: 180860

Disease characteristics

Excerpted from the GeneReview: Silver-Russell Syndrome
Silver-Russell Syndrome (SRS) is typically characterized by gestational growth restriction resulting in affected individuals being born small for gestational age, with relative macrocephaly at birth (head circumference ≥1.5 standard deviations [SD] above birth weight and/or length), prominent forehead with frontal bossing, and frequently body asymmetry. This is typically followed by postnatal growth failure, and in some cases progressive limb length discrepancy and feeding difficulties. Additional clinical features include triangular facies, fifth finger clinodactyly, and micrognathia with narrow chin. Except for the limb length asymmetry, growth failure is proportionate and head growth typically normal. The average adult height in untreated individuals is ~3.1±1.4 SD below the mean. The Netchine-Harbison Clinical Scoring System (NH-CSS) is a sensitive diagnostic scoring system. Clinical diagnosis can be established in an individual who meets at least four of the NH-CSS clinical criteria – prominent forehead/frontal bossing and relative macrocephaly at birth plus two additional findings – and in whom other disorders have been ruled out. [from GeneReviews]
Authors:
Howard M Saal  |  Madeleine D Harbison  |  Irene Netchine   view full author information

Clinical features

From HPO
Craniopharyngioma
MedGen UID:
41339
Concept ID:
C0010276
Neoplastic Process
A benign pituitary-region neoplasm that originates from Rathke's pouch. Craniopharyngiomas are benign slow growing tumors that are located within the sellar and para sellar region of the central nervous system.
Nephroblastoma
MedGen UID:
10221
Concept ID:
C0027708
Neoplastic Process
The presence of a nephroblastoma, which is a neoplasm of the kidney that primarily affects children.
Testicular seminoma
MedGen UID:
1790467
Concept ID:
C5551428
Neoplastic Process
The presence of a seminoma, an undifferentiated germ cell tumor of the testis.
Congenital posterior urethral valve
MedGen UID:
451008
Concept ID:
C0238506
Congenital Abnormality
A developmental defect resulting in an obstructing membrane in the posterior male urethra.
Urethral valve
MedGen UID:
120573
Concept ID:
C0266345
Congenital Abnormality
The presence of an abnormal membrane obstructing the urethra.
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Abnormality of the ureter
MedGen UID:
374455
Concept ID:
C1840382
Finding
An abnormality of the ureter. The ureter is the duct by which urine passes from the kidney to the bladder.
Syndactyly
MedGen UID:
52619
Concept ID:
C0039075
Congenital Abnormality
Webbing or fusion of the fingers or toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the fingers or toes in a proximo-distal axis are referred to as "symphalangism".
Short middle phalanx of the 5th finger
MedGen UID:
322335
Concept ID:
C1834060
Anatomical Abnormality
Hypoplastic/small middle phalanx of the fifth finger.
Short distal phalanx of the 5th finger
MedGen UID:
373146
Concept ID:
C1836674
Finding
Hypoplastic/small distal phalanx of the fifth finger.
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Abnormality of the cardiovascular system
MedGen UID:
116727
Concept ID:
C0243050
Congenital Abnormality
Any abnormality of the cardiovascular system.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Hepatocellular carcinoma
MedGen UID:
389187
Concept ID:
C2239176
Neoplastic Process
Hepatocellular carcinoma is the major histologic type of malignant primary liver neoplasm. It is the fifth most common cancer and the third most common cause of death from cancer worldwide. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Hepatoblastomas comprise 1 to 2% of all malignant neoplasms of childhood, most often occurring in children under 3 years of age. Hepatoblastomas are thought to be derived from undifferentiated hepatocytes (Taniguchi et al., 2002).
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.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Delayed cranial suture closure
MedGen UID:
75805
Concept ID:
C0277828
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Fasting hypoglycemia
MedGen UID:
75765
Concept ID:
C0271708
Disease or Syndrome
HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
Downturned corners of mouth
MedGen UID:
356471
Concept ID:
C1866195
Anatomical Abnormality
A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.
Craniofacial disproportion
MedGen UID:
357916
Concept ID:
C1867114
Finding
Cafe-au-lait spot
MedGen UID:
113157
Concept ID:
C0221263
Finding
Cafe-au-lait spots are hyperpigmented lesions that can vary in color from light brown to dark brown with smooth borders and having a size of 1.5 cm or more in adults and 0.5 cm or more in children.
Decreased response to growth hormone stimulation test
MedGen UID:
1784655
Concept ID:
C5539399
Finding
Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.
Blue sclerae
MedGen UID:
154236
Concept ID:
C0542514
Finding
An abnormal bluish coloration of the sclera.

Professional guidelines

PubMed

Wakeling EL, Brioude F, Lokulo-Sodipe O, O'Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Grønskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A, Maghnie M, Mohnike K, Monk D, Moore GE, Murray PG, Ogata T, Petit IO, Russo S, Said E, Toumba M, Tümer Z, Binder G, Eggermann T, Harbison MD, Temple IK, Mackay DJ, Netchine I
Nat Rev Endocrinol 2017 Feb;13(2):105-124. Epub 2016 Sep 2 doi: 10.1038/nrendo.2016.138. PMID: 27585961
Marsaud C, Rossignol S, Tounian P, Netchine I, Dubern B
Arch Dis Child 2015 Apr;100(4):353-8. Epub 2014 Nov 18 doi: 10.1136/archdischild-2013-305864. PMID: 25700540
Eggermann T, Begemann M, Binder G, Spengler S
Orphanet J Rare Dis 2010 Jun 23;5:19. doi: 10.1186/1750-1172-5-19. PMID: 20573229Free PMC Article

Curated

Eggermann T, Buiting K, Temple IK
Eur J Hum Genet 2011 Mar;19(3) Epub 2010 Dec 8 doi: 10.1038/ejhg.2010.202. PMID: 21150879Free PMC Article

Recent clinical studies

Etiology

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group
N Engl J Med 2021 Feb 4;384(5):403-416. Epub 2020 Dec 30 doi: 10.1056/NEJMoa2035389. PMID: 33378609Free PMC Article
Wakeling EL, Brioude F, Lokulo-Sodipe O, O'Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Grønskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A, Maghnie M, Mohnike K, Monk D, Moore GE, Murray PG, Ogata T, Petit IO, Russo S, Said E, Toumba M, Tümer Z, Binder G, Eggermann T, Harbison MD, Temple IK, Mackay DJ, Netchine I
Nat Rev Endocrinol 2017 Feb;13(2):105-124. Epub 2016 Sep 2 doi: 10.1038/nrendo.2016.138. PMID: 27585961
INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fätkenheuer G, Llibre JM, Molina JM, Munderi P, Schechter M, Wood R, Klingman KL, Collins S, Lane HC, Phillips AN, Neaton JD
N Engl J Med 2015 Aug 27;373(9):795-807. Epub 2015 Jul 20 doi: 10.1056/NEJMoa1506816. PMID: 26192873Free PMC Article
Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators
N Engl J Med 2015 Jun 18;372(25):2387-97. Epub 2015 Jun 3 doi: 10.1056/NEJMoa1410489. PMID: 26039521
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M
N Engl J Med 2009 Sep 10;361(11):1045-57. Epub 2009 Aug 30 doi: 10.1056/NEJMoa0904327. PMID: 19717846

Diagnosis

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group
N Engl J Med 2021 Feb 4;384(5):403-416. Epub 2020 Dec 30 doi: 10.1056/NEJMoa2035389. PMID: 33378609Free PMC Article
Wakeling EL, Brioude F, Lokulo-Sodipe O, O'Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Grønskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A, Maghnie M, Mohnike K, Monk D, Moore GE, Murray PG, Ogata T, Petit IO, Russo S, Said E, Toumba M, Tümer Z, Binder G, Eggermann T, Harbison MD, Temple IK, Mackay DJ, Netchine I
Nat Rev Endocrinol 2017 Feb;13(2):105-124. Epub 2016 Sep 2 doi: 10.1038/nrendo.2016.138. PMID: 27585961
Binder G, Begemann M, Eggermann T, Kannenberg K
Best Pract Res Clin Endocrinol Metab 2011 Feb;25(1):153-60. doi: 10.1016/j.beem.2010.06.005. PMID: 21396582
Wakeling EL
Arch Dis Child 2011 Dec;96(12):1156-61. Epub 2011 Feb 24 doi: 10.1136/adc.2010.190165. PMID: 21349887
Eggermann T
Am J Med Genet C Semin Med Genet 2010 Aug 15;154C(3):355-64. doi: 10.1002/ajmg.c.30274. PMID: 20803658

Therapy

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group
N Engl J Med 2021 Feb 4;384(5):403-416. Epub 2020 Dec 30 doi: 10.1056/NEJMoa2035389. PMID: 33378609Free PMC Article
Wakeling EL, Brioude F, Lokulo-Sodipe O, O'Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Grønskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A, Maghnie M, Mohnike K, Monk D, Moore GE, Murray PG, Ogata T, Petit IO, Russo S, Said E, Toumba M, Tümer Z, Binder G, Eggermann T, Harbison MD, Temple IK, Mackay DJ, Netchine I
Nat Rev Endocrinol 2017 Feb;13(2):105-124. Epub 2016 Sep 2 doi: 10.1038/nrendo.2016.138. PMID: 27585961
INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fätkenheuer G, Llibre JM, Molina JM, Munderi P, Schechter M, Wood R, Klingman KL, Collins S, Lane HC, Phillips AN, Neaton JD
N Engl J Med 2015 Aug 27;373(9):795-807. Epub 2015 Jul 20 doi: 10.1056/NEJMoa1506816. PMID: 26192873Free PMC Article
Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis BS, Ophuis TO, Jukema JW, De Ferrari GM, Ruzyllo W, De Lucca P, Im K, Bohula EA, Reist C, Wiviott SD, Tershakovec AM, Musliner TA, Braunwald E, Califf RM; IMPROVE-IT Investigators
N Engl J Med 2015 Jun 18;372(25):2387-97. Epub 2015 Jun 3 doi: 10.1056/NEJMoa1410489. PMID: 26039521
Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA; PLATO Investigators, Freij A, Thorsén M
N Engl J Med 2009 Sep 10;361(11):1045-57. Epub 2009 Aug 30 doi: 10.1056/NEJMoa0904327. PMID: 19717846

Prognosis

El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, Campbell TB, Clark J, Jackson LA, Fichtenbaum CJ, Zervos M, Rankin B, Eder F, Feldman G, Kennelly C, Han-Conrad L, Levin M, Neuzil KM, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Polakowski L, Mascola JR, Ledgerwood JE, Graham BS, August A, Clouting H, Deng W, Han S, Leav B, Manzo D, Pajon R, Schödel F, Tomassini JE, Zhou H, Miller J; COVE Study Group
N Engl J Med 2021 Nov 4;385(19):1774-1785. Epub 2021 Sep 22 doi: 10.1056/NEJMoa2113017. PMID: 34551225Free PMC Article
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group
N Engl J Med 2021 Feb 4;384(5):403-416. Epub 2020 Dec 30 doi: 10.1056/NEJMoa2035389. PMID: 33378609Free PMC Article
Masunaga Y, Inoue T, Yamoto K, Fujisawa Y, Sato Y, Kawashima-Sonoyama Y, Morisada N, Iijima K, Ohata Y, Namba N, Suzumura H, Kuribayashi R, Yamaguchi Y, Yoshihashi H, Fukami M, Saitsu H, Kagami M, Ogata T
J Clin Endocrinol Metab 2020 Jan 1;105(1) doi: 10.1210/clinem/dgz034. PMID: 31544945
INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fätkenheuer G, Llibre JM, Molina JM, Munderi P, Schechter M, Wood R, Klingman KL, Collins S, Lane HC, Phillips AN, Neaton JD
N Engl J Med 2015 Aug 27;373(9):795-807. Epub 2015 Jul 20 doi: 10.1056/NEJMoa1506816. PMID: 26192873Free PMC Article
Wakeling EL
Arch Dis Child 2011 Dec;96(12):1156-61. Epub 2011 Feb 24 doi: 10.1136/adc.2010.190165. PMID: 21349887

Clinical prediction guides

Dunkle LM, Kotloff KL, Gay CL, Áñez G, Adelglass JM, Barrat Hernández AQ, Harper WL, Duncanson DM, McArthur MA, Florescu DF, McClelland RS, Garcia-Fragoso V, Riesenberg RA, Musante DB, Fried DL, Safirstein BE, McKenzie M, Jeanfreau RJ, Kingsley JK, Henderson JA, Lane DC, Ruíz-Palacios GM, Corey L, Neuzil KM, Coombs RW, Greninger AL, Hutter J, Ake JA, Smith K, Woo W, Cho I, Glenn GM, Dubovsky F; 2019nCoV-301 Study Group
N Engl J Med 2022 Feb 10;386(6):531-543. Epub 2021 Dec 15 doi: 10.1056/NEJMoa2116185. PMID: 34910859Free PMC Article
Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, Diemert D, Spector SA, Rouphael N, Creech CB, McGettigan J, Khetan S, Segall N, Solis J, Brosz A, Fierro C, Schwartz H, Neuzil K, Corey L, Gilbert P, Janes H, Follmann D, Marovich M, Mascola J, Polakowski L, Ledgerwood J, Graham BS, Bennett H, Pajon R, Knightly C, Leav B, Deng W, Zhou H, Han S, Ivarsson M, Miller J, Zaks T; COVE Study Group
N Engl J Med 2021 Feb 4;384(5):403-416. Epub 2020 Dec 30 doi: 10.1056/NEJMoa2035389. PMID: 33378609Free PMC Article
Masunaga Y, Inoue T, Yamoto K, Fujisawa Y, Sato Y, Kawashima-Sonoyama Y, Morisada N, Iijima K, Ohata Y, Namba N, Suzumura H, Kuribayashi R, Yamaguchi Y, Yoshihashi H, Fukami M, Saitsu H, Kagami M, Ogata T
J Clin Endocrinol Metab 2020 Jan 1;105(1) doi: 10.1210/clinem/dgz034. PMID: 31544945
Binder G, Begemann M, Eggermann T, Kannenberg K
Best Pract Res Clin Endocrinol Metab 2011 Feb;25(1):153-60. doi: 10.1016/j.beem.2010.06.005. PMID: 21396582
Eggermann T
Am J Med Genet C Semin Med Genet 2010 Aug 15;154C(3):355-64. doi: 10.1002/ajmg.c.30274. PMID: 20803658

Recent systematic reviews

Singh A, Pajni K, Panigrahi I, Khetarpal P
Curr Pediatr Rev 2023;19(2):157-168. doi: 10.2174/1573396318666220315142542. PMID: 35293298
Cortessis VK, Azadian M, Buxbaum J, Sanogo F, Song AY, Sriprasert I, Wei PC, Yu J, Chung K, Siegmund KD
J Assist Reprod Genet 2018 Jun;35(6):943-952. Epub 2018 Apr 25 doi: 10.1007/s10815-018-1173-x. PMID: 29696471Free PMC Article

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