Cranial pathologies in Noonan syndrome: clinical implications for pre-growth hormone neuroimaging

Noonan syndrome (NS) is a multisystem disorder caused by mutations affecting the RAS-MAPK signaling pathway and is associated with an increased risk of proliferative disorders. This study aimed to evaluate the frequency and spectrum of cranial pathologies in patients with NS and to assess their clinical significance. This cross-sectional study included patients with NS followed between January 2000 and January 2025. Clinical, anthropometric, laboratory, and cranial MRI data obtained at diagnosis and during follow-up were retrospectively reviewed. Statistical analyses were performed using SPSS version 29.0. Cranial abnormalities were identified in 54.1% of patients with NS. The identified abnormalities ranged from structural anomalies to clinically significant intracranial tumors. The asymptomatic nature of some lesions suggests that clinical evaluation alone may be insufficient. The absence of newly detected pathologies or malignancies during follow-up in patients receiving growth hormone therapy supports its safety. These findings support consideration of cranial MRI at the time of diagnosis in patients with NS.

Cranial abnormalities are common in patients with NS and encompass a broad spectrum ranging from structural anomalies to clinically significant neoplastic lesions. The presence of asymptomatic lesions suggests that clinical evaluation alone may be insufficient for their detection. Cranial MRI at the time of diagnosis may facilitate the early identification of clinically relevant intracranial abnormalities. The absence of malignancy during follow-up supports the safety of recombinant growth hormone therapy in this population.

• Noonan syndrome is associated with abnormalities of the RAS-MAPK signaling pathway and an increased risk of proliferative disorders. • Data regarding cranial MRI findings in patients with Noonan syndrome are limited and mainly derived from small case series.

• More than half of the patients with Noonan syndrome had cranial MRI abnormalities, including a broad spectrum of structural lesions and clinically significant intracranial neoplasms. • Clinically significant lesions may remain asymptomatic, supporting consideration of cranial MRI at the time of diagnosis, particularly before initiation of growth hormone therapy.