Endocrine Abstracts

JOINT3233

Introduction: Spinal deformities are frequently observed in individuals with Rasopathies, with manifestations varying from scoliosis and kyphoscoliosis to isolated kyphosis, suggesting the role of the RAS/MAPK pathway in bone remodeling. According to recent studies, scoliosis and kyphosis are manifestations reported in 15% of patients with Noonan syndrome (NS) and 20-35% of individuals with Cardiofaciocutaneous syndrome (CFC). However, the exact prevalence and progression of spinal deformities in Rasopathies remain unclear, warranting further investigation.

Objective: To evaluate the frequency of spinal deformities in patients with Rasopathies. Study design and participants: This retrospective observational study was conducted in two tertiary hospitals. One hundred patients were selected (51 males, 49 females; 52 PTPN11, 10 BRAF, 9 SOS1, 5 RAF1, 5 LZTR1, 4 SHOC2, 4 KRAS, 4 RIT1, 2 MEK1, 2 NRAS, 1 SOS2, 1 NF1, and 1 A2ML1) among who underwent spinal radiographs as part of clinical investigation of Rasopathies.

Methods: We analyzed medical records regarding clinical characteristics and the presence of spinal deformities.

Results: From 88 patients with NS, 8 with CFCS, 1 with Neurofibromatosis type 1 (NF1), and 3 with NS with multiple lentigines ((NSML), we found 52 individuals with spinal deformities (52%): 32 with scoliosis, 8 with kyphoscoliosis, 2 with kyphosis, 2 with lordosis, and 20 with other alterations. Seventeen patients presented two or more associated spinal deformities. Regarding Rashopathies, 43 out of 88 patients with NS presented spinal deformities (49%), 29 patients with scoliosis (2 needing orthopedic braces), 5 with kyphoscoliosis, and 2 with kyphosis. All six patients with CFC syndrome (100%) presented spinal deformities, such as 1 with scoliosis and 3 with kyphoscoliosis. Two out of 3 patients with NSML (67%) showed scoliosis. One patient with NF1 showed anterior vertebral scalloping.

Conclusions: We observed a higher frequency of spinal deformities in our cohort than what is reported in the literature. Understanding Rasopathies’ genetic and biological mechanisms could lead to new therapeutic targets for skeletal abnormalities and other manifestations of these disorders.