Silver–Russell Syndrome: from Molecular Pathogenesis to Clinical Management

초록

Silver–Russell syndrome (SRS) is a rare imprinting disorder characterized by prenatal and postnatal growth retardation, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties. The estimated incidence ranges from 1 in 30,000 to 1 in 100,000 live births. Diagnosis is primarily clinical, supported by the Netchine–Harbison Clinical Scoring System (NH-CSS), while molecular confirmation is achieved in approximately 60% of cases. The two major genetic mechanisms are loss of methylation (LOM) at chromosome 11p15 and maternal uniparental disomy for chromosome 7 (upd(7)mat); rarer causes include abnormalities involving chromosomes 14q32, 20, and 16, or mutations in CDKN1C or IGF2. Management focuses on optimizing nutrition, preventing hypoglycemia, and addressing growth failure. Growth hormone (GH) therapy effectively improves height, body composition, and appetite in most patients, though partial IGF-1 resistance may occur, particularly in 11p15 LOM. Puberty often begins early and progresses rapidly, contributing to compromised final height; combined GH and GnRH analogue therapy may be beneficial in selected cases. Long-term follow-up is required to monitor metabolic outcomes and support individualized care based on molecular subtype. A multidisciplinary approach remains essential to address the complex endocrine, nutritional, and developmental challenges of SRS throughout childhood and adolescence.

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