Approach to the patient with suspected Silver-Russell syndrome.
Uttara KurupDavid Boon Ngan LimHelena PalauAvinaash V MaharajMiho IshidaJustin Huw DaviesHelen L StorrPublished in: The Journal of clinical endocrinology and metabolism (2024)
Silver-Russell Syndrome (SRS) is a clinical diagnosis requiring the fulfilment of ≥4/6 Netchine-Harbison Clinical Scoring System (NH-CSS) criteria. A score of ≥4/6 (or ≥3/6 with strong clinical suspicion) NH-CSS warrants (epi)genetic confirmation as an underlying cause can be identified in ∼60% patients. The approach to the investigation and diagnosis of SRS is detailed in the only international consensus guidance, published in 2016. In the intervening years, the clinical, biochemical, and (epi)genetic characteristics of SRS have rapidly expanded, largely attributable to advancing molecular genetic techniques and a greater awareness of related disorders. The commonest etiologies of SRS remain loss of methylation of chromosome 11p15 (11p15LOM) and maternal uniparental disomy of chromosome 7 (upd(7)mat). Rarer causes of SRS include monogenic pathogenic variants in imprinted (CDKN1C and IGF2) and non-imprinted (PLAG1 and HMGA2) genes. Although the age-specific NH-CSS can identify commoner molecular causes of SRS, its use in identifying monogenic causes is unclear. Preliminary data suggest NH-CSS is poor at identifying many of these cases. Additionally, there has been increased recognition of conditions with phenotypes overlapping with SRS that may fulfil NH-CSS criteria but have distinct genetic aetiologies and disease trajectories. This group of conditions is frequently overlooked and under-investigated, leading to no or delayed diagnosis. Like SRS, these conditions are multisystem disorders requiring multidisciplinary care and tailored management strategies. Early identification is crucial to improve outcomes and reduce the major burden of the diagnostic odyssey for patients and families. This article aims to enable clinicians to identify key features of rarer causes of SRS and conditions with overlapping phenotypes, show a logical approach to the molecular investigation and highlight the differences in clinical management strategies.
Keyphrases
- genome wide
- copy number
- end stage renal disease
- room temperature
- ejection fraction
- chronic kidney disease
- newly diagnosed
- healthcare
- gold nanoparticles
- dna methylation
- palliative care
- case report
- type diabetes
- gene expression
- mass spectrometry
- randomized controlled trial
- metabolic syndrome
- body mass index
- cell proliferation
- risk factors
- single molecule
- machine learning
- patient reported outcomes
- adipose tissue
- binding protein
- electronic health record
- physical activity
- big data
- weight loss
- pregnancy outcomes
- patient reported
- genome wide analysis