Endocrine Abstracts

JOINT1760

Background: Silver-Russell syndrome (SRS) is a rare (epi)genetic disorder characterized by severe intrauterine and postnatal growth retardation, relative macrocephaly at birth, prominent forehead, body asymmetry and early feeding difficulties. Primary molecular causes are loss of methylation within the 11p15. 5 imprinting control region (H19/IGF2) [11p15 LOM] and maternal uniparental disomy of chromosome 7, [upd(7)mat]. While feeding difficulties are a key feature of SRS, gastrointestinal manifestations were first described in 2014 by Marsaud et al. In 2015, the first international consensus on SRS was published, providing standardized recommendations. It remains unclear whether these recommendations have influenced management and subsequently the nutritional status and of patients born after this publication.

Objective: To assess the evolution of gastrointestinal and nutritional manifestations in SRS patients born after the 2015 international consensus and compare findings to previous data published in 2014 for patients followed in the same center.

Subjects and Methods: A retrospective study included 56 patients born after the consensus publication (n = 42 with 11p15 LOM and n = 14 with upd(7)mat). Nutritional status, gastrointestinal manifestations (feeding difficulties, gastroesophageal reflux disease [GERD], vomiting, constipation), and management (nutritional enrichment, requirement and modality of enteral nutrition, treatments) were analyzed.

Results: Nutritional status at 2 years old (BMI, weight-to-height ratio (W/H)), as well as the prevalence of GERD and vomiting, remained comparable to those reported by Marsaud et al. However, constipation prevalence was significantly higher (50% vs. 20%, P < 0. 05). The proportion of patients requiring enteral nutrition remained stable (temporary nasogastric tube or gastrostomy), but the percentage of gastrostomy was significantly lower (10. 7% vs. 21%, P < 0. 05) than those reported in the previous study. Notably, patients with maternal uniparental disomy of chromosome 7 (upd(7)mat) underwent gastrostomy more frequently than those with 11p15 LOM (35. 7 % vs 2. 4%, P < 0. 05). Additionally, 48. 2% of patients received cyproheptadine treatment (an H1 antihistamine with an orexigenic effect) with a significant improvement in W/H ratio at six months following its introduction (+3. 59%, 95% CI [1. 069; 6. 107]).

Conclusion: Gastrointestinal and nutritional issues remain a major concern in SRS. The implementation of the 2015 international consensus has led to improve identification of symptoms such as constipation, better nutritional status through targeted therapeutic strategies such as cyproheptadine (mentioned in the 2015 consensus as a therapy to evaluate) and/or early Growth Hormone therapy, and to a significant reduction of gastrostomy implemented, reflecting an evolution in clinical management.