Endocrine Abstracts

JOINT672

Introduction: Noonan Syndrome (NS) is a genetic disorder characterized by typical facial dysmorphisms, short stature, and congenital heart defects. Several genes have been implicated; approximately 50% of affected individuals present alterations in the PTPN11 gene, involved in the RAS/MAPK pathway.

Aim: To characterize NS patients followed in the Paediatric Endocrinology Unit in a tertiary hospital from the centre region of Portugal.

Methods: Patients diagnosed with NS and followed in the pediatric endocrinology unit between 2009 and 2024 were identified, and demographic and clinical data were collected.

Results: Eighteen patients diagnosed with NS were identified, of whom 12 (66.7%) were boys. The main reason for referral to the Paediatric Endocrinology Unit was short stature (77.8%), followed by poor weight gain (11.1%) and delayed puberty (11.1%). At the first consultation, patients had a median age of 8.3 years (IQR: 3.7-12.3), although their median age at diagnosis was 3.5 years (IQR: 1.7-10.2). Patients presented with typical facial features (88.9%), cardiac defects (61.1%), stature below P3 (77.8%), pectus excavatum (27.8%), developmental delay (44.4%), lymphatic defects (22.2%), and confirmed family history (11.1%), and suspected family history (5.6%). Cryptorchidism was present in 41.7% of boys. Molecular studies were available in 15 cases, identifying mutations in PTPN11 (66.7%), SOS1 (13.3%), BRAF (6.7%), LZTR1 (6.7%), and NF1 (6.7%). The median height z-score at the first consultation was -2.6 (IQR: 1,5), confirming the short stature in 14 patients (77.8%). The median z-score for target height was -0.3 (IQR: 0.7). The final height was available for 7 patients, corresponding to a median height z-score of -1.6 (IQR: 1.7) and a median difference of -1.9 (IQR: 2.6) compared to the target height z-score. At follow-up, only 3 patients presented growth hormone deficiency, receiving an average dose of recombinant human growth hormone (rhGH) 0.029 mg/kg/day (min. 0.021; max. 0.034) for 52 months (min. 16; max. 88). At the last evaluation, 7 (38.9%) patients were prepubertal, and 6 (33.3%) exhibited delayed puberty. Twelve (66,7%) patients exhibited varying neurodevelopmental delays or learning difficulties.

Discussion: The multisystemic involvement of NS requires a multidisciplinary team approach. Paediatric Endocrinology plays a key role in addressing short stature and pubertal development. Despite the approval of rhGH for the treatment of NS in Europe, the conditions for initiating therapy depend on the regulations of each member state. The rhGH improves final height, mainly when initiated early and maintained for a more extended period before the onset of puberty.