Role of imprinting disorders in short children born SGA and Silver-Russell syndrome spectrum

Like Comment


(Epi)genetic disorders associated with small-for-gestational-age with short stature (SGA-SS) include imprinting disorders (IDs). Silver-Russell syndrome (SRS) is a representative ID in SGA-SS and has heterogenous (epi)genetic causes.

Subjects and Methods

To clarify the contribution of IDs to SGA-SS and the molecular and phenotypic spectrum of SRS, we recruited 269 patients with SGA-SS consisting of 103 and 166 patients referred to us for genetic testing for SGA-SS and SRS, respectively. After excluding 20 patients with structural abnormalities detected by comparative genomic hybridization analysis using catalog array, 249 patients were classified into three subgroups based on the Netchine-Harbison clinical scoring system (NH-CSS), SRS diagnostic criteria. We screened various IDs by methylation analysis for differentially methylated regions (DMRs) related to known IDs. We also performed clinical analysis.


These 249 patients with SGA-SS were classified into ‘SRS-compatible group’ (n=148), ‘non-SRS with normocephaly or relative macrocephaly at birth group’ (non-SRS group) (n=94), or ‘non-SRS with relative microcephaly at birth group’ (non-SRS with microcephaly group) (n=7). The 44.6% of patients in ‘SRS-compatible group’, 21.3% of patients in ‘non-SRS group’, and 14.3% in ‘non-SRS with microcephaly group’ had various IDs. Loss of methylation of the H19/IGF2:intergenic-DMR and uniparental disomy chromosome 7, being major genetic causes of SRS, were detected in 30.4% of patients in ‘SRS-compatible group’ and in 13.8% of patients in ‘non-SRS group’.


We clarified the contribution of IDs as (epi)genetic causes of SGA-SS and the molecular and phenotypic spectrum of SRS. Various IDs constitute underlying factors for SGA-SS, including SRS.

View the full article @ The Journal of clinical endocrinology and metabolism

Get PDF with LibKey


The wider, wiser view for healthcare professionals. ClinOwl signposts the latest clinical content from over 100 leading medical journals.
6577 Contributions
0 Following