Diffuse Midline Glioma (DMG)
Diffuse midline glioma (DMG, H3 K27-altered) is a highly aggressive brain tumor arising in midline structures (brainstem, thalamus, spinal cord) in children. Formerly known as diffuse intrinsic pontine glioma (DIPG), it is classified as grade 4 in the World Health Organization (WHO) classification.
Última atualização: 2026-06-06
Definition
Diffuse midline glioma is a grade 4 glial tumor defined in the WHO 2021 classification of central nervous system tumors as an H3 K27-altered molecular variant. It most often develops in the pons of the brainstem and, owing to its diffusely infiltrative nature, cannot be surgically removed. It is among the leading causes of childhood brain-tumor mortality.
Epidemiology
DMG occurs most frequently in children aged 5-10 years; roughly 10-20% of cases present in adulthood and tend to follow a more indolent course. It accounts for about 10-15% of childhood brain tumors. By location, approximately 75-80% are pontine (brainstem), 15-20% thalamic and 5% spinal.
Molecular Pathogenesis
The defining molecular feature is the H3 K27M mutation, occurring in the H3F3A or HIST1H3B/C genes, which disrupts chromatin regulation and causes epigenetic dysregulation. Co-occurring alterations include TP53 mutations, PDGFRA amplification and ACVR1 mutation; the latter is associated with a relatively better course.
Symptoms
In pontine DMG the earliest and most typical findings are cranial nerve deficits: double vision, facial asymmetry, and difficulty swallowing or speaking. These are accompanied by pyramidal (long-tract) signs such as weakness and spasticity, and by ataxia. This triad of cranial nerve deficit, long-tract signs and ataxia forms the classic picture. Thalamic tumors cause unilateral weakness and sensory loss, while spinal tumors cause progressive weakness and a sensory level. Symptoms usually progress rapidly, often within less than six months.
Diagnosis
Contrast-enhanced brain MRI is the first-line study. Typical pontine DMG appears as a diffuse lesion involving more than half of the pons, markedly hyperintense on T2/FLAIR with variable enhancement. In pontine cases with typical imaging and a consistent clinical picture, the diagnosis can often be made on imaging alone. Stereotactic biopsy is considered for atypical appearances, thalamic location, or when molecular profiling is needed for targeted therapy. Definitive diagnosis rests on demonstrating the H3 K27M mutant protein and glial markers (GFAP) on tissue analysis.
Treatment
Surgical resection is not feasible because of the diffusely infiltrative growth; surgery is limited to biopsy in selected cases and to drainage for hydrocephalus. The standard treatment is focal radiotherapy (about 54 Gy), which provides temporary clinical improvement in most patients but is not curative. Conventional chemotherapy offers limited survival benefit. In 2025 dordaviprone (ONC201) received accelerated approval in the United States for recurrent H3 K27M-mutant DMG; it is not yet licensed in Türkiye, where access may be possible through clinical trials or international routes. Care is planned by a multidisciplinary neuro-oncology team.
Prognosis
DMG remains an aggressive, non-curable disease with current treatment; median survival is reported as 9-12 months in the literature. Adult age, ACVR1 mutation and thalamic location are relatively more favorable, whereas pontine location and TP53 mutation are less favorable. New targeted therapies and drug-delivery methods are under intensive investigation. Outcomes vary from patient to patient and no outcome can be guaranteed; psychological support and palliative care for families are integral to management.
Referências
- Greenberg MS. Greenberg's Handbook of Neurosurgery. 10th ed. Thieme; 2023:683.
- Osborn AG, Hedlund GL, Salzman KL. Osborn's Brain: Imaging, Pathology, and Anatomy. 2nd ed. Elsevier; 2018:511.
- Louis DN, et al. The 2021 WHO Classification of Tumors of the Central Nervous System. Neuro Oncol. 2021.
Este artigo é informativo e não substitui um exame médico. As decisões de diagnóstico e tratamento são individuais.