Endocrine Abstracts

JOINT1470

Background: Silver-Russell Syndrome (SRS) is a rare imprinting disorder characterized by intrauterine growth restriction, postnatal growth failure, and distinctive craniofacial features. While physical manifestations of SRS are well-documented, its impact on intellectual and developmental functions remains less understood. This study aims to evaluate cognitive and developmental outcomes in children with SRS to enhance understanding and improve clinical interventions.

Methods: To investigate if children with SRS have increased prevalence of cognitive disabilities, as well as autism spectrum disorder. A cohort of 28 children (16 boys), mean age 11.6 years, were diagnosed with SRS and recruited from the Pediatric National Growth Hormone Registry. Children were followed at the national expert centre for SRS due to growth hormone treatment. Griffith’s Mental Developmental scales and Wechsler Intelligence Scales were used according to age. Parents answered Autism Spectrum Screening Questionnaire (ASSQ) and autism diagnosis information was collected from medical records.

Results: In 12 children (43% of the cohort) we identified loss of methylation of chromosome 11p15 (n = 11) and maternal uniparental disomy of chromosome 7 (n = 1), in remain 16/28 no molecular cause was identified. The intelligence quotient (IQ) range was broad (61–142). Notably, 12 out of 28 children had an IQ below 85 (-1 SD), including 3 with an IQ below 70 (-2 SD), reflecting possible difficulties in learning and academic achievement. The mean full-scale IQ was significantly lower in “clinical SRS” compared to those with epigenetically confirmed SRS, 85.9 (15.8) and 104.9 (19.3), respectively. An uneven IQ profile between verbal IQ (VIQ) and performance IQ (PIQ) was observed in 14/26 children (54%), with nine of those showing a higher VIQ than PIQ. There was no significant association between molecular confirmed SRS and clinical SRS and uneven VIQ-PIQ profile. In 21/28 children one parent completed the ASSQ. Four children (two with and two without a clinical ASD diagnosis) scored above the cut-off (≥17), indicating autism-related symptoms. Six additional children reached either ASSQ cut off scores or had a diagnosis of Asperger´s syndrome.

Conclusion: Children with SRS present with variable intellectual and developmental outcomes, often exhibiting specific cognitive weaknesses and adaptive behavior challenges. Furthermore, ASD may be present. These findings underscore the need for early neurodevelopmental assessments to optimize learning and social adaptation.