Diffuse midline glioma, H3K27-altered*, referred to as DMG, is a malignant glial tumor. It occurs in the midline of the brain or spinal cord and is most commonly seen in children.
*80% of DMGs have the H3K27 mutation. DMGs that do not have this mutation are still called diffuse midline glioma, H3K27-altered.
Location
DMGs occur primarily in one of these areas of the central nervous system:
- Midline of brain:
- Brainstem (mainly located in the pons), the portion of the brain that controls many critical functions integral to life including breathing; DMG of the pons may be referred to as DIPG, diffuse intrinsic pontine glioma
- Thalamus (one or both thalami may be involved), the portion of the brain with roles in consciousness, memory, and relaying sensory and motor signals to and from the brain
- Spinal cord, which controls movement and sensation
Symptoms
The symptoms of DMG are dependent on the tumor location. The most common symptoms of brainstem DMG are cranial nerve abnormalities (crossed eyes or lazy eye, drooping eyelids, double vision, difficulty swallowing), difficulty walking, balance issues, and arm or leg weakness. DMG of the thalamus may cause symptoms including confusion, headaches, nausea/vomiting, numbness, visual changes, and impaired movement or speech. Spinal cord DMGs commonly are associated with impaired movement, numbness, and alteration of normal bowel and bladder function. Patients usually seek medical attention two months or less from the start of symptoms. While the diagnosis of DMG can often be made with imaging (i.e., MRI) alone without the need for a surgical biopsy, tumor biopsy by a qualified neurosurgeon is recommended to obtain information of the molecular make-up of the tumor, which can help to guide treatment, as well as to confirm the diagnosis.
Treatment
Complete or partial surgical removal of the tumor is often not feasible due to the delicate locations in which DMGs occur and the shape of the tumor (no clear tumor border). However, tumor biopsy should be strongly considered to obtain information of the molecular profile of the tumor, as certain molecular features offer additional treatment options including medications or clinical trials. Radiation therapy is the only treatment that has shown benefit in DMG. There are numerous clinical trials for DMGs, both at the time of diagnosis (with or following radiation) or at the time of disease progression.
Prognosis
Prognosis means a prediction of outcome. This information is usually based on information gathered from groups of people with the same disease. It is important to remember these statistics are not individualized.
With radiation therapy, the median survival of patients with DMG is 9-18 months. More than 99% of patients die of the disease within 5 years after diagnosis.
Incidence
Approximately 200-400 children are diagnosed with DMG in the United States each year. DMG comprise up to 20% of pediatric brain tumors.
Age Distribution
The most common age at diagnosis of DMG of the pons is 5-10 years old. DMG is rare in adolescents and adults.
Risk Factors
Molecular Profile
Molecular profiling is the detection of specific genes, proteins, or other molecules in a tumor. This information helps confirm tumor diagnosis, inform treatment options, and predict prognosis.
The majority of DMGs (around 80%) have a characteristic mutation in the H3 protein known as H3K27M. Some DMG have additional mutations in other genes, including ACVR1, ATRX, BMI1, EZHIP, PIK3CA, PPM1D, or TP53. Clinical trials that target some of these molecular changes may be available.
Additional Resources
Content last reviewed:
Nov 2024 by Holly B. Lindsay, MD, MS and Daniela M. Ciccolini, MSN, RN, CPNP, CPHON
