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Silver-russell syndrome 4(SRS4)

MedGen UID:
1712866
Concept ID:
C5394450
Disease or Syndrome
Synonyms: SILVER-RUSSELL SYNDROME 4; SRS4
 
Gene (location): PLAG1 (8q12.1)
 
Monarch Initiative: MONDO:0030118
OMIM®: 618907

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

Additional description

From OMIM
Silver-Russell syndrome-4 (SRS4) is characterized by intrauterine growth retardation followed by feeding difficulties and postnatal growth restriction. Dysmorphic facial features include triangular face and prominent forehead, and relative macrocephaly at birth may be observed (Abi Habib et al., 2018). For a discussion of genetic heterogeneity of Silver-Russell syndrome, see SRS1 (180860).  http://www.omim.org/entry/618907

Clinical features

From HPO
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.
Birth length less than 3rd percentile
MedGen UID:
340924
Concept ID:
C1855650
Finding
Decreased body weight
MedGen UID:
1806755
Concept ID:
C5574742
Finding
Abnormally low body weight.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Mild microcephaly
MedGen UID:
332294
Concept ID:
C1836806
Congenital Abnormality
Decreased occipito-frontal (head) circumference (OFC). For the microcephaly OFC must be between -3 SD and -2 SD compared to appropriate, age matched, normal standards (i.e. -3 SD <= OFC < -2 SD).
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.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.

Professional guidelines

PubMed

Giabicani E, Pham A, Brioude F, Mitanchez D, Netchine I
Best Pract Res Clin Endocrinol Metab 2018 Aug;32(4):523-534. Epub 2018 Apr 5 doi: 10.1016/j.beem.2018.03.013. PMID: 30086872
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

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
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

Świąder-Leśniak A, Jurkiewicz D, Kołodziejczyk H, Kozłowska A, Korpysz A, Szalecki M, Chrzanowska K
Endokrynol Pol 2023;74(3):285-293. Epub 2023 Jun 19 doi: 10.5603/EP.a2023.0042. PMID: 37335065
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
Eggermann T, Davies JH, Tauber M, van den Akker E, Hokken-Koelega A, Johansson G, Netchine I
Genes (Basel) 2021 Apr 17;12(4) doi: 10.3390/genes12040585. PMID: 33920525Free PMC Article
Spiteri BS, Stafrace Y, Calleja-Agius J
Neonatal Netw 2017 Jul 1;36(4):206-212. doi: 10.1891/0730-0832.36.4.206. PMID: 28764823
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

Therapy

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
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

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
Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO, Storr HL
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4716-e4733. doi: 10.1210/clinem/dgab437. PMID: 34136918Free 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
Hattori H, Hiura H, Kitamura A, Miyauchi N, Kobayashi N, Takahashi S, Okae H, Kyono K, Kagami M, Ogata T, Arima T
Clin Epigenetics 2019 Feb 7;11(1):21. doi: 10.1186/s13148-019-0623-3. PMID: 30732658Free PMC Article
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

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
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
Meyer R, Soellner L, Begemann M, Dicks S, Fekete G, Rahner N, Zerres K, Elbracht M, Eggermann T
J Pediatr 2017 Aug;187:206-212.e1. Epub 2017 May 19 doi: 10.1016/j.jpeds.2017.04.018. PMID: 28529015
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
Giabicani E, Netchine I, Brioude F
Curr Opin Pediatr 2016 Aug;28(4):529-35. doi: 10.1097/MOP.0000000000000379. PMID: 27386972

Recent systematic reviews

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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