Objective:

Background:

Noonan syndrome is a single gene disorder caused by pathogenic variants disrupting the Ras/mitogen-activated protein kinase pathway, implicated in neuro-oncogenesis. Individuals with Noonan syndrome have a higher risk of cancer, with hematological malignancies, neuroblastomas, and primary brain tumors (e.g., DNETs and low-grade gliomas) reported.

Design/Methods:

Cases were drawn from our largest-to-date neuroimaging study of children with Noonan syndrome (n=61), aged 6-16 years. We collected T1- and T2-weighted structural brain MRI scans and medical history, and obtained follow-up clinical imaging and outside radiology reports for subjects in whom MVNT-like lesions were identified. Research MRI scans were interpreted by a board-certified neuroradiologist.

Results:

Six children with Noonan syndrome associated with PTPN11 variants (four females, ages 11-16) demonstrated MVNT-like lesions (6/61, 9.83%). Two presented with lateral parietal lesions, two had temporal lesions, one demonstrated a multicentric lesion spanning the left lateral parietal and right precuneus regions, and one had a lateral precentral gyrus lesion. Contrast enhanced clinical MRIs and/or outside radiology reports for four children corroborated research MRI findings. Five children were currently or previously on growth hormone, and three had a history of headaches. No children had a history of seizures.

Conclusions:

MVNT-like lesions are observed in children with Noonan syndrome and PTPN11 variants. Further studies are warranted to evaluate the factors associated with increased frequency of MVNT-like lesions in these children.