Atypical teratoid rhabdoid tumor, or ATRT, is one of the most aggressive brain cancers in children. It is classified as a grade 4 tumor, the highest and most serious grade in the World Health Organization’s system. ATRT is rare, with fewer than 100 new cases diagnosed in the United States each year, and it predominantly strikes very young children. It is the most common malignant brain tumor in infants under one year old.
Where ATRT Grows and Why
ATRT develops from several types of immature embryonal cells, which is part of what makes it so unusual. Unlike many brain tumors that arise from a single cell type, ATRT contains a mix of cell types, including rhabdoid, neuroepithelial, epithelial, and mesenchymal cells. This mixture of cell origins is what gives the tumor its name: “teratoid” refers to its tissue diversity.
These tumors can form anywhere in the central nervous system. In the brain, they commonly arise in the cerebellum and brainstem (the back and lower portions of the brain), as well as in the cerebral hemispheres, ventricles, and other deep structures. ATRT can also begin in the spinal cord, though this is less common. One distinctive feature is that ATRT frequently involves the cerebellopontine angle, the space near where the brainstem meets the cerebellum, which helps distinguish it from other pediatric brain tumors like medulloblastoma.
The underlying driver of ATRT is the loss of a protein called INI1, which normally acts as a tumor suppressor. When the gene responsible for making this protein (called SMARCB1) is deleted or mutated on both copies, cells lose a critical brake on growth. Pathologists confirm an ATRT diagnosis by staining tumor tissue and looking for the complete absence of INI1 in the nuclei of tumor cells.
Symptoms in Infants and Young Children
ATRT is a fast-growing tumor, so symptoms often appear suddenly and worsen over days or weeks rather than months. Because the tumor most often affects children age three and younger, the signs can be easy to mistake for common childhood illnesses. In infants, one of the most telling symptoms is an unusual increase in head size, caused by fluid buildup in the brain that the tumor blocks from draining normally.
Other symptoms to watch for include:
- Morning headaches or headaches that improve after vomiting
- Nausea and vomiting
- Unusual sleepiness or a noticeable change in energy and activity level
- Loss of balance, poor coordination, or difficulty walking
- Pain, tingling, numbness, or weakness in the face
Because infants and toddlers can’t describe headaches or vision changes, parents often notice behavioral shifts first: a baby who becomes unusually irritable, stops reaching milestones, or loses skills they recently developed.
How ATRT Is Diagnosed
Imaging is the first step. On an MRI, ATRT tends to look different from other common pediatric brain tumors. Compared with medulloblastoma (the tumor it’s most often confused with), ATRT more frequently contains areas of internal bleeding, visible in nearly half of cases. ATRT tumors also tend to have a more mixed appearance, with both solid and cystic components, while medulloblastomas are almost always solid.
About a quarter of children with ATRT already have spinal metastases (tumor cells that have traveled down the spinal cord) at the time of diagnosis. For this reason, imaging of the entire spine is typically performed alongside the brain MRI.
A definitive diagnosis requires a tissue sample from surgery. Pathologists then test the tumor for the loss of INI1 protein. When all tumor cell nuclei lack this protein, and genetic testing confirms deletions or mutations in the SMARCB1 gene, the diagnosis of ATRT is confirmed.
Treatment Approach
There is no single established standard treatment for ATRT. Instead, children are treated with a combination of surgery, chemotherapy, and sometimes radiation therapy, and many are enrolled in clinical trials that are actively refining these protocols.
Surgery to remove as much of the tumor as possible is the first priority. How completely the tumor can be removed is one of the strongest predictors of how well a child will do. After surgery, intensive chemotherapy follows. Many current protocols use high-dose chemotherapy followed by a procedure called stem cell rescue, where a child’s own blood-forming stem cells (collected before chemotherapy) are returned to help the body recover from the powerful drugs.
One of the largest prospective studies, conducted through the Children’s Oncology Group, treated children with intensive chemotherapy followed by high-dose chemotherapy with stem cell rescue and radiation therapy. The four-year progression-free survival rate was 37%, and overall survival was 43%. These numbers reflect how difficult ATRT remains to treat, but also how far outcomes have improved from earlier decades when the diagnosis was almost uniformly fatal.
Radiation therapy poses a particular challenge because most patients are under three years old. Radiation to a developing brain carries significant risks to cognitive development, so doctors weigh its benefits carefully and sometimes delay it or use more targeted approaches.
Survival Rates and What Affects Them
The five-year relative survival rate for ATRT is about 48% for children up to age 14, 42% for teenagers and young adults ages 15 to 39, and 25% for adults 40 and older. Average survival times in studies range from 12 to 24 months, though many children live longer with aggressive treatment.
Several factors influence the outlook. Children diagnosed at age three or older generally do better than infants, partly because they can tolerate more aggressive treatment, including radiation. Complete surgical removal of the tumor improves survival significantly. Whether the tumor has already spread at the time of diagnosis also matters: localized ATRT that can be fully removed and treated intensively carries the best prognosis.
Life After Treatment for Survivors
Children who survive ATRT face long-term effects from the treatments that saved their lives. The combination of brain surgery, high-dose chemotherapy, and radiation therapy takes a measurable toll on the developing brain. In a study of over 200 adult survivors of childhood brain tumors at St. Jude, 20% to 30% showed severe impairment in intelligence, memory, and executive function (skills like planning and mental flexibility). In the general population, that level of impairment occurs in only about 2% of people.
IQ scores in children treated with cranial radiation typically begin to decline two to five years after diagnosis and continue dropping for five to ten years afterward. The younger the child at the time of treatment, the greater the impact. Affected children often struggle with processing speed, attention, reading, and math, even if their overall intelligence remains in a functional range. Survivors who received whole-brain radiation are 1.5 to 3 times more likely to develop severe cognitive impairment than those who did not.
Hearing loss is another common late effect, particularly from the platinum-based chemotherapy drugs used in ATRT treatment. Children are more vulnerable to this type of hearing damage than adults. The hearing loss is typically permanent, affects both ears, and begins in the high-frequency range before progressing to the speech frequencies with higher cumulative drug exposure. Risk factors include younger age at treatment, higher total doses of platinum drugs, and having received cranial radiation on top of chemotherapy.
Targeted Therapies Under Investigation
Because ATRT is driven by a specific genetic defect, the loss of the SMARCB1 gene and its INI1 protein, researchers are testing drugs that exploit this vulnerability. One promising approach targets an enzyme called EZH2, which becomes overactive when INI1 is missing. A drug called tazemetostat blocks EZH2 and is already FDA-approved for another INI1-deficient cancer (epithelioid sarcoma).
A Phase I/II clinical trial at Boston Children’s Hospital is currently testing tazemetostat in combination with two immunotherapy drugs in children with INI1-deficient tumors, including ATRT. The trial is studying both the safety of this three-drug combination and whether it can effectively treat these cancers. This represents a shift toward therapies that target the specific molecular defect in ATRT rather than relying solely on the broad-spectrum approach of conventional chemotherapy and radiation.