Lokulo-Sodipe, O;
Ballard, L;
Child, J;
Inskip, HM;
Byrne, CD;
Ishida, M;
Moore, GE;
... Temple, IK; + view all
(2020)
Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood.
Journal of Medical Genetics
10.1136/jmedgenet-2019-106561.
(In press).
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Abstract
BACKGROUND: Silver-Russell syndrome is an imprinting disorder that restricts growth, resulting in short adult stature that may be ameliorated by treatment. Approximately 50% of patients have loss of methylation of the imprinting control region (H19/IGF2:IG-DMR) on 11p15.5 and 5%-10% have maternal uniparental disomy of chromosome 7. Most published research focuses on the childhood phenotype. Our aim was to describe the phenotypic characteristics of older patients with SRS. / METHODS: A retrospective cohort of 33 individuals with a confirmed molecular diagnosis of SRS aged 13 years or above were carefully phenotyped. / RESULTS: The median age of the cohort was 29.6 years; 60.6% had a height SD score (SDS) ≤-2 SDS despite 70% having received growth hormone treatment. Relative macrocephaly, feeding difficulties and a facial appearance typical of children with SRS were no longer discriminatory diagnostic features. In those aged ≥18 years, impaired glucose tolerance in 25%, hypertension in 33% and hypercholesterolaemia in 52% were noted. While 9/33 accessed special education support, university degrees were completed in 40.0% (>21 years). There was no significant correlation between quality of life and height SDS. 9/25 were parents and none of the 17 offsprings had SRS. / CONCLUSION: Historical treatment regimens for SRS were not sufficient for normal adult growth and further research to optimise treatment is justified. Clinical childhood diagnostic scoring systems are not applicable to patients presenting in adulthood and SRS diagnosis requires molecular confirmation. Metabolic ill-health warrants further investigation but SRS is compatible with a normal quality of life including normal fertility in many cases.
| Type: | Article |
|---|---|
| Title: | Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1136/jmedgenet-2019-106561 |
| Publisher version: | http://dx.doi.org/10.1136/jmedgenet-2019-106561 |
| Language: | English |
| Additional information: | This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Silver Russell syndrome, imprinting, short stature, uniparental disomy |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10092223 |
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