Hereditary nervous system / brain tumours

Genetic testing is clinically relevant for the following indications, including but not limited to:

• Children with a CNS tumour subtype strongly linked to a predisposition syndrome, such as atypical teratoid/rhabdoid tumour, choroid plexus carcinoma or medulloblastoma
• Patients who meet established clinical diagnostic criteria for a tumour predisposition syndrome, for example neurofibromatosis type 1
• Children diagnosed with retinoblastoma, particularly bilateral or multifocal early-onset disease
• Individuals whose personal or family history is suggestive of Li-Fraumeni syndrome or a related heritable cancer syndrome

Testing is typically requested by paediatric oncologists, neuro-oncologists, ophthalmologists and clinical geneticists.

Germline testing is used when a CNS tumour presentation or family history suggests an inherited predisposition, and it informs surveillance decisions. For example, around 40% of retinoblastoma cases are heritable, carrying a constitutional (germline) RB1 variant.

A pathogenic or likely pathogenic variant establishes the specific molecular diagnosis, identifying the causative gene and predisposition syndrome. A variant of uncertain significance (VUS) is an unclear finding: current evidence is insufficient to classify it as likely benign or likely pathogenic, and reanalysis can be offered after a few years as evidence accumulates. In other cases, no pathogenic variant is detected in the analysed genes. The presence of a pathogenic variant cannot, however, be entirely excluded: the causative change may lie in a gene not yet linked to the condition, or in a regulatory region that current methods cannot reliably capture.

Each variant is classified according to ACMG/AMP criteria.

When a pathogenic variant is identified, syndrome-specific tumour surveillance and risk-reducing management can be established, since carriers face elevated lifetime risks of multiple tumours. The result also enables predictive (cascade) testing of at-risk relatives, allowing early surveillance for carriers and reassurance for non-carriers. Reproductive options can be discussed where relevant.

Medical genetic counselling is an important part of the testing process. It helps patients and families understand the test, interpret results, and make well-informed medical decisions, and it supports physicians in delivering informed care. Availability of genetic counselling services may vary by country, so please contact us to check access in your region.

Testing uses next-generation sequencing (NGS) based multi-gene panels.

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