Medulloblastoma, macrocephaly, and a pathogenic germline PTEN variant: Cause or coincidence?

Medulloblastomas (MBs) are a heterogeneous group of childhood brain tumors with four consensus subgroups, namely MB_SHH , MB_WNT , MB_{Group 3} , and MB_{Group 4} , representing the second most common type of pediatric brain cancer after high-grade gliomas. They suffer from a high prevalence of genetic predisposition with up to 20% of MB_SHH caused by germline mutations in only six genes. However, the spectrum of germline mutations in MB_SHH remains incomplete.

Comprehensive Next-Generation Sequencing panels of both tumor and patient blood samples were performed as molecular genetic characterization. The panels cover genes that are known to predispose to cancer.

Here, we report on a patient with a pathogenic germline PTEN variant resulting in an early stop codon p.(Glu7Argfs*4) (ClinVar ID: 480383). The patient developed macrocephaly and MB_SHH , but reached remission with current treatment protocols.

We propose that pathogenic PTEN variants may predispose to medulloblastoma, and show that remission was reached with current treatment protocols. The PTEN gene should be included in the genetic testing provided to patients who develop medulloblastoma at an early age. We recommend brain magnetic resonance imaging upon an unexpected acceleration of growth of head circumference for pediatric patients harboring pathogenic germline PTEN variants.