Human Development and Health, Faculty of Medicine University of Southampton, Southampton, UK.
Department of Paediatric Endocrinology, University Hospital Southampton NHS Foundations Trust, Southampton, UK.
J Med Genet. 2020 Oct;57(10):683-691. doi: 10.1136/jmedgenet-2019-106561. Epub 2020 Feb 13.
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.
A retrospective cohort of 33 individuals with a confirmed molecular diagnosis of SRS aged 13 years or above were carefully phenotyped.
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.
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.
银-鲁综合征是一种印记障碍，限制了生长，导致成年身高矮小，但治疗后可能会有所改善。大约 50%的患者在 11p15.5 上存在印迹控制区（H19/IGF2:IG-DMR）的甲基化缺失，5%-10%的患者存在 7 号染色体的母源单亲二体性。大多数已发表的研究都集中在儿童表型上。我们的目的是描述年长的 SRS 患者的表型特征。
对 33 名年龄在 13 岁及以上、经分子诊断确诊为 SRS 的患者进行回顾性队列研究，并对其进行仔细的表型分析。
该队列的中位年龄为 29.6 岁；尽管 70%的患者接受了生长激素治疗，但身高标准差（SDS）≤-2 SDS 的患者占 60.6%。相对的大头畸形、喂养困难和典型的 SRS 患儿面容已不再是具有鉴别诊断意义的特征。在年龄≥18 岁的患者中，25%存在糖耐量受损，33%存在高血压，52%存在高胆固醇血症。虽然 9/33 人接受了特殊教育支持，但仍有 40.0%（>21 岁）的人完成了大学学位。生活质量与身高 SDS 之间无显著相关性。9/25 人是父母，而 17 个子女中没有 SRS 患者。
SRS 的历史治疗方案不足以促进正常的成年生长，需要进一步研究以优化治疗。适用于儿童的临床诊断评分系统不适用于成年患者，SRS 的诊断需要分子学确认。代谢不良需要进一步调查，但 SRS 在许多情况下与正常的生活质量是兼容的，包括正常的生育能力。
