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Silver-russell syndrome 2(SRS2)

MedGen UID:
1714148
Concept ID:
C5394446
Disease or Syndrome
Synonym: UNIPARENTAL DISOMY, MATERNAL, CHROMOSOME 7
 
Monarch Initiative: MONDO:0030116
OMIM®: 618905

Disease characteristics

Excerpted from the GeneReview: Silver-Russell Syndrome
Silver-Russell Syndrome (SRS) is typically characterized by asymmetric gestational growth restriction resulting in affected individuals being born small for gestational age, with relative macrocephaly at birth (head circumference ≥1.5 SD above birth weight and/or length), prominent forehead usually with frontal bossing, and frequently body asymmetry. This is 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, the growth failure is proportionate and head growth 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

Additional description

From OMIM
Silver-Russell syndrome-2 (SRS2) is characterized by pre- and postnatal growth retardation, with relative sparing of cranial growth, triangular facies, and downturned corners of the mouth. Fifth-finger clinodactyly and facial, limb, or truncal asymmetry are also frequently present (summary by Monk et al., 2000). For a discussion of genetic heterogeneity of Silver-Russell syndrome, see SRS1 (180860).  http://www.omim.org/entry/618905

Clinical features

From HPO
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).
2-3 toe syndactyly
MedGen UID:
1645640
Concept ID:
C4551570
Congenital Abnormality
Syndactyly with fusion of toes two and three.
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.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Mild global developmental delay
MedGen UID:
861405
Concept ID:
C4012968
Finding
A mild delay in the achievement of motor or mental milestones in the domains of development of a child.
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 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.
Relative macrocephaly
MedGen UID:
338607
Concept ID:
C1849075
Congenital Abnormality
A relatively mild degree of macrocephaly in which the head circumference is not above two standard deviations from the mean, but appears dysproportionately large when other factors such as body stature are taken into account.
Delayed closure of the anterior fontanelle
MedGen UID:
825928
Concept ID:
C3840083
Finding
A delay in closure (ossification) of the anterior fontanelle, which generally undergoes closure around the 18th month of life.
Neonatal hypoglycemia
MedGen UID:
57646
Concept ID:
C0158986
Finding
Blood glucose concentration below the lower limit of established reference ranges in a newborn.
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.
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Thin skin
MedGen UID:
140848
Concept ID:
C0423757
Finding
Reduction in thickness of the skin, generally associated with a loss of suppleness and elasticity of the skin.
Blue sclerae
MedGen UID:
154236
Concept ID:
C0542514
Finding
An abnormal bluish coloration of the sclera.

Professional guidelines

PubMed

Smeets CC, Renes JS, van der Steen M, Hokken-Koelega AC
J Clin Endocrinol Metab 2017 Mar 1;102(3):983-991. doi: 10.1210/jc.2016-3388. PMID: 28001454
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

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
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
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
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

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
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
Espay AJ, Chen R
Continuum (Minneap Minn) 2013 Oct;19(5 Movement Disorders):1264-86. doi: 10.1212/01.CON.0000436156.54532.1a. PMID: 24092290
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

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
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
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

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
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
Binder G, Schweizer R, Blumenstock G, Ferrand N
J Clin Endocrinol Metab 2017 Nov 1;102(11):4100-4108. doi: 10.1210/jc.2017-00874. PMID: 28945864

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
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
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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