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Original research
Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood
  1. Oluwakemi Lokulo-Sodipe1,2,
  2. Lisa Ballard3,
  3. Jenny Child4,
  4. Hazel M Inskip5,
  5. Christopher D Byrne1,6,
  6. Miho Ishida7,
  7. Gudrun E Moore7,
  8. Emma L Wakeling8,
  9. Angela Fenwick9,
  10. Deborah J G Mackay1,10,
  11. Justin Huw Davies1,11,
  12. I Karen Temple1,12
  1. 1Human Development and Health, Faculty of Medicine University of Southampton, Southampton, UK
  2. 2Department of Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  3. 3Cancer Sciences, University of Southampton Faculty of Medicine, Southampton, UK
  4. 4Child Growth Foundation, Sutton Coldfield, Birmingham, UK
  5. 5MRC Epidemiology Unit, University of Southampton Faculty of Medicine, Southampton, UK
  6. 6NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  7. 7Great Ormond Street Institute of Child Health, University College London, London, UK
  8. 8Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
  9. 9Clinical Ethics and Law at Southampton (CELS), Faculty of Medicine University of Southampton, Southampton, UK
  10. 10Wessex Regional Genetics Laboratory, Salisbury Hospital NHS Foundation Trust, Salisbury, Wiltshire, UK
  11. 11Department of Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  12. 12Wessex Clinical Genetics Service, University Hospital Southampton NHS Foundation Trust, Southampton, UK
  1. Correspondence to Professor I Karen Temple, Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton SO165YA, UK; ikt{at}soton.ac.uk

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.

  • imprinting
  • Silver Russell syndrome
  • short stature
  • uniparental disomy
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Footnotes

  • Presented at This paper presents independent research funded by the Child Growth Foundation and the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-1111-26003).

  • Contributors OL-S carried out, analysed and reported the data in the project. JC supported the planning and delivery of this paper from a patient perspective. HMI, CDB, ELW, LB, AF, DJGM advised on the planning, analysis and reporting of data. GEM and MI contributed significant patients to the study and reporting of data. JHD and IKT planned and delivered the research. All authors contributed to the writing of the document. IKT is overall responsible for the research.

  • Funding 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).

  • Disclaimer The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval Ethics approval for this study was granted (REC reference: 13/SC/0630).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. The data are deidentified participant data and this paper needs to be acknowledged if the data are to be reused.

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