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Height and body mass index in molecularly-confirmed Silver-Russell syndrome and the long-term effects of growth hormone treatment

Height and body mass index in molecularly-confirmed Silver-Russell syndrome and the long-term effects of growth hormone treatment
Height and body mass index in molecularly-confirmed Silver-Russell syndrome and the long-term effects of growth hormone treatment

Objective: Silver–Russell syndrome (SRS) causes short stature. Growth hormone (GH) treatment aims to increase adult height. However, data are limited on the long-term outcomes of GH in patients with molecularly confirmed SRS. This study evaluated height, body mass index (BMI) and GH treatment in molecularly confirmed SRS. Design: An observational study with retrospective data collection. Patients: Individuals with molecularly confirmed SRS aged ≥13 years. Measurements: Data were collected on height, height gain (change in height standard deviation score [SDS] from childhood to final or near-final height), BMI and gain in BMI (from childhood to adulthood) and previous GH treatment. Results: Seventy-one individuals (40 female) were included. The median age was 22.0 years (range 13.2–69.7). The molecular diagnoses: H19/IGF2:IG-DMR LOM in 80.3% (57/71); upd(7)mat in 16.9% (12/71) and IGF2 mutation in 2.8% (2/71). GH treatment occurred in 77.5% (55/71). Total height gain was greater in GH-treated individuals (median 1.53 SDS vs. 0.53 SDS, p =.007), who were shorter at treatment initiation (−3.46 SDS vs. −2.91 SDS, p =.04) but reached comparable heights to GH-untreated individuals (−2.22 SDS vs. −2.74 SDS, p =.7). In GH-treated individuals, BMI SDS was lower at the most recent assessment (median −1.10 vs. 1.66, p =.002) with lower BMI gain (2.01 vs. 3.58, p =.006) despite similar early BMI SDS to GH-untreated individuals (median −2.65 vs. −2.78, p =.3). Conclusions: These results support the use of GH in SRS for increasing height SDS. GH treatment was associated with lower adult BMI which may reflect improved metabolic health even following discontinuation of therapy.

Silver–Russell syndrome, body mass index, growth hormone, height, weight
0300-0664
284-292
Lokulo-Sodipe, Oluwakemi
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Giabicani, E
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Canton, APM
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Ferrand, N
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Child, J
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Wakeling, EL
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Binder, G
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Netchine, I
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Mackay, Deborah
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Inskip, Hazel
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Byrne, Christopher
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Temple, Karen
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Davies, Justin
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Lokulo-Sodipe, Oluwakemi
d428f857-0e58-4964-b1f0-136af7432805
Giabicani, E
dddf3d43-4091-4635-a8bd-0e7e8b1a9383
Canton, APM
06900ab7-177a-425c-9293-cca174f90199
Ferrand, N
d27568de-3f96-4c93-9a62-a38df0726409
Child, J
7e6641e4-a0ef-450f-9195-8f87127bcba4
Wakeling, EL
d902fa28-0b9f-4409-a140-8af1d2837ac6
Binder, G
1b58b8c6-4dc4-46bc-a0f7-32768ed75f14
Netchine, I
060d209d-c133-4593-a396-a44282a3dd85
Mackay, Deborah
588a653e-9785-4a00-be71-4e547850ee4a
Inskip, Hazel
5fb4470a-9379-49b2-a533-9da8e61058b7
Byrne, Christopher
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Temple, Karen
d63e7c66-9fb0-46c8-855d-ee2607e6c226
Davies, Justin
9f18fcad-f488-4c72-ac23-c154995443a9

Lokulo-Sodipe, Oluwakemi, Giabicani, E, Canton, APM, Ferrand, N, Child, J, Wakeling, EL, Binder, G, Netchine, I, Mackay, Deborah, Inskip, Hazel, Byrne, Christopher, Temple, Karen and Davies, Justin (2022) Height and body mass index in molecularly-confirmed Silver-Russell syndrome and the long-term effects of growth hormone treatment. Clinical Endocrinology, 97 (3), 284-292. (doi:10.1111/cen.14715).

Record type: Article

Abstract

Objective: Silver–Russell syndrome (SRS) causes short stature. Growth hormone (GH) treatment aims to increase adult height. However, data are limited on the long-term outcomes of GH in patients with molecularly confirmed SRS. This study evaluated height, body mass index (BMI) and GH treatment in molecularly confirmed SRS. Design: An observational study with retrospective data collection. Patients: Individuals with molecularly confirmed SRS aged ≥13 years. Measurements: Data were collected on height, height gain (change in height standard deviation score [SDS] from childhood to final or near-final height), BMI and gain in BMI (from childhood to adulthood) and previous GH treatment. Results: Seventy-one individuals (40 female) were included. The median age was 22.0 years (range 13.2–69.7). The molecular diagnoses: H19/IGF2:IG-DMR LOM in 80.3% (57/71); upd(7)mat in 16.9% (12/71) and IGF2 mutation in 2.8% (2/71). GH treatment occurred in 77.5% (55/71). Total height gain was greater in GH-treated individuals (median 1.53 SDS vs. 0.53 SDS, p =.007), who were shorter at treatment initiation (−3.46 SDS vs. −2.91 SDS, p =.04) but reached comparable heights to GH-untreated individuals (−2.22 SDS vs. −2.74 SDS, p =.7). In GH-treated individuals, BMI SDS was lower at the most recent assessment (median −1.10 vs. 1.66, p =.002) with lower BMI gain (2.01 vs. 3.58, p =.006) despite similar early BMI SDS to GH-untreated individuals (median −2.65 vs. −2.78, p =.3). Conclusions: These results support the use of GH in SRS for increasing height SDS. GH treatment was associated with lower adult BMI which may reflect improved metabolic health even following discontinuation of therapy.

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SRS - final height and BMI revised - Accepted Manuscript
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Clinical Endocrinology - 2022 - Lokulo‐Sodipe - Height and body mass index in molecularly confirmed Silver Russell syndrome - Version of Record
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Accepted/In Press date: 21 February 2022
e-pub ahead of print date: 21 March 2022
Published date: 1 September 2022
Additional Information: Funding Information: The Child Growth Foundation supported the Study of Adults and Adolescents with Russell–Silver syndrome in the recruitment of study participants and by providing a grant to fund body composition analysis. Association Française des Familles ayant un enfant atteint du Syndrome Silver‐Russell ou né Petit pour l'Âge Gestationnel (AFIF/PAG) supported the French cohort. The Study of Adults and Adolescents with Russell–Silver syndrome was funded by the UK National Institute of Health Research, Research for patient benefit grant PB‐PG‐1111‐26003. The research received support from NIHR CRN: Wessex, NIHR Southampton BRC and NIHR Wellcome Trust Southampton Clinical Research Facility. CDB and IKT are supported in part by the Southampton NIHR Biomedical Research Centre, UK (2017‐2022.IS‐BRC‐1215‐20004). Publisher Copyright: © 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.
Keywords: Silver–Russell syndrome, body mass index, growth hormone, height, weight

Identifiers

Local EPrints ID: 455984
URI: http://eprints.soton.ac.uk/id/eprint/455984
ISSN: 0300-0664
PURE UUID: f85dc24e-82bb-4219-9297-584855de31dd
ORCID for Oluwakemi Lokulo-Sodipe: ORCID iD orcid.org/0000-0002-8169-3384
ORCID for Deborah Mackay: ORCID iD orcid.org/0000-0003-3088-4401
ORCID for Hazel Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for Christopher Byrne: ORCID iD orcid.org/0000-0001-6322-7753
ORCID for Karen Temple: ORCID iD orcid.org/0000-0002-6045-1781

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Date deposited: 11 Apr 2022 17:21
Last modified: 17 Mar 2024 07:11

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Contributors

Author: Oluwakemi Lokulo-Sodipe ORCID iD
Author: E Giabicani
Author: APM Canton
Author: N Ferrand
Author: J Child
Author: EL Wakeling
Author: G Binder
Author: I Netchine
Author: Deborah Mackay ORCID iD
Author: Hazel Inskip ORCID iD
Author: Karen Temple ORCID iD
Author: Justin Davies

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