Silver-Russell syndrome secondary to rare (epi)genotypes exhibits phenotypic heterogeneity challenging clinical diagnosis.

ABSTRACT:

Context

Silver-Russell syndrome (SRS) is a complex multisystem condition requiring timely diagnosis for appropriate management. A clinical diagnosis is made in individuals scoring ≥ 4 Netchine-Harbison Clinical Scoring System (NH-CSS) criteria, with (epi)genetic investigations undertaken in those with NH-CSS ≥ 3 and strong clinical suspicion. Monogenic variants in imprinted (CDKN1C and IGF2) and non-imprinted (HMGA2 and PLAG1) genes are recognised as rare causes of SRS. The frequency of associated phenotypes is unclear.

Objective

We evaluated the suitability of SRS as an umbrella term for these (epi)genotypes by identifying key clinical features and assessing the validity of NH-CSS.

Methods

An extensive literature search identified 22 IGF2, 18 HMGA2, 11 CDKN1C and 11

SUBMITTER: Kurup U 

PROVIDER: S-EPMC12723925 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature