ESPE Abstracts

Background: Noonan syndrome (NS) is a condition caused by pathogenic variants of the genes of the RAS-MAPK pathway. Its clinical manifestations are diverse and include congenital heart disease, short stature, ocular abnormalities, coagulation defects and structural renal anomalies. Our aim was to find out whether the patients with a genetic diagnosis of NS in the West of Scotland were managed according to the Management of Noonan Syndrome guidelines (DYSCERNE), with a focus on referrals for full cardiac evaluation, renal ultrasound, assessment of vision, coagulation screen, and referrals to endocrinology. We also analysed patterns of referrals between the different specialties.

Methods: Using the clinical and laboratory databases, we identified patients with possible NS in the West of Scotland over the 10-year period of 2011 to 2021. This included patients with a definitive genetic diagnosis as well as patients with a variant of unknown/uncertain significance (VUS). Clinical information and growth data were obtained from electronic records. A t-test was used to determine the significance in height difference between groups referred and not referred to endocrinology.

Results: 45 patients were identified; 40 had a definitive genetic diagnosis and 5 had a VUS with clinical features of NS. 96% of them had been seen by cardiology, but only 64% and 60% had had a coagulation screen and an assessment of their vision respectively. The renal ultrasound assessment was at 36% only. 12 patients were referred to endocrinology, although only 2 of them received Growth Hormone Therapy (GHT). Patients who were referred were generally shorter than those not referred. (Median Height SDS -2.17; Range, -4.09 to -1.28 for those referred, and Median Height SDS,-1.82; Range, -2.78 to -0.56 for those not referred). Paediatrics made the majority of referrals (from a single specialty) to genetics (58%) and endocrinology (56%) while genetics made the highest number of referrals to cardiology (50%). There were no referrals to endocrinology by genetics.

Conclusion: While most patients were referred for cardiology assessment, there is still much work to be done to improve referrals for renal ultrasound, assessment of vision and coagulation screen. The variation in management highlights the lack of awareness of the guidelines and the need for a lead physician/ MDT clinic to co-ordinate the assessments. The absence of referrals to endocrinology by genetics could be because GHT was not licensed for NS in Europe until recently; now that it is, we expect an increase in referrals to endocrinology.