Diagnosis and management of Silver-Russell syndrome: second international consensus statement

This international Consensus Statement updates 2016 guidelines for diagnosis and management of individuals with Silver-Russell syndrome (SRS), using a Delphi-like process to reach agreement through iterative expert discussions, based on published data and/or expert opinion. Individuals referred with suspected SRS show substantial clinical and genetic heterogeneity. Advances in genomic and epigenomic technology highlight the need for strict, primarily molecular, criteria for diagnosis, which should be made in those with maternal uniparental disomy for chromosome 7 (upd(7)mat) or 11p15 loss of methylation at H19/IGF2:intergenic differentially methylated region (IG-DMR) (due to an imprinting change, copy number variant or upd(11)mat). Molecular stratification enables tailoring of care pathways towards specific genetic and/or epigenetic subgroups. More widely, recommendations are relevant to other growth-related imprinting disorders (including Temple syndrome) and conditions affecting the insulin-like growth factor 2 pathway. An expert, multidisciplinary approach is required, focusing on growth failure, early severe feeding difficulties, later possible rapid weight gain, abnormal body composition, gastrointestinal problems, hypoglycaemia, insulin resistance, accelerated puberty, body asymmetry, neurocognitive issues and psychosocial challenges. Evidence published since the first Consensus Statement highlights the increased risk of metabolic disease from adolescence into adulthood. These updated recommendations have important implications for accurate diagnosis and optimal life-long management of individuals with SRS.