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Also called: ALK-related neuroblastic tumor susceptibility, PHOX2B-related neuroblastic tumor susceptibility
Neuroblastoma is a cancer of the nerve cells. It mainly affects children before age 5. It rarely occurs in adults. In 1–2% of cases, an increased chance of developing neuroblastoma can be inherited from a parent. This is called hereditary neuroblastoma.
Neuroblastoma develops when young nerve cells (neuroblasts) grow uncontrollably to form a tumor. Most neuroblastomas start in the nerve tissue of the adrenal glands. These glands are small, hormone-producing organs that are on top of each kidney. Sometimes neuroblastomas begin in the nerve cells of the abdomen, chest, neck, or pelvis.
Neuroblastoma is found most often in children who have no family history of the disease. This is called sporadic neuroblastoma.
Hereditary neuroblastoma is caused by changes in 1 of 2 genes: ALK or PHOX2B. Children with hereditary neuroblastoma are more likely to have a higher number of tumors. They are also more likely to be diagnosed at a younger age than people with sporadic neuroblastoma.
People with hereditary neuroblastoma are at increased risk to develop tumors. These tumors include:
Hereditary neuroblastoma often varies in how severe it is, even among people in the same family. Some people may have multiple tumors. Others do not develop any tumors. Even within the same person, some tumors might shrink and go away on their own. Other tumors may be aggressive and continue to grow.
The risk of developing a tumor is highest in infancy. This risk decreases by late childhood. People with an ALK mutation have a 50–60% chance of developing a tumor.
Not all mutations in PHOX2B increase a person’s risk for neuroblastoma. Instead, there are specific mutations that increase tumor risk. The exact tumor risk for people with PHOX2B is not known because these mutations are much less common. If a person is diagnosed with a mutation in PHOX2B that increases a section of the gene to 29-33 repeats (known as polyalanine repeat mutations, PARMs) or if a mutation is outside of this gene repeat section (known as a non-polyalanine repeat mutation, NPARM), these people have a higher risk and should be screened for neuroblastoma.
Your geneticist, genetic counselor or other health care provider can help you determine what type of PHOX2B mutation you have.
People with hereditary neuroblastoma may have symptoms of their tumor. These people may have:
Patients with PHOX2B mutations may have conditions that affect the nervous system. These include:
These neurological conditions are not seen in people with ALK mutations.
Hereditary neuroblastoma is caused by changes in 1 of 2 genes: ALK or PHOX2B. The ALK and PHOX2B genes control how and when nerve cells grow, divide, and die. Researchers believe that ALK and PHOX2B mutations lead to neuroblastoma by influencing the growth and development of neural cells, which makes them more likely to become cancerous.
Most people without hereditary neuroblastoma carry 2 working copies of the ALK and PHOX2B genes in their cells. One copy comes from each parent.
Cells from people with hereditary neuroblastoma carry 1 working copy of the ALK or PHOX2B gene and 1 copy that is changed. This change (a mutation) causes the gene to not work right. Hereditary neuroblastoma is more commonly caused by ALK mutations than PHOX2B mutations.
Most children with hereditary neuroblastoma caused by a mutation in the ALK gene have inherited the mutation from a parent. Some children with ALK gene mutations are the first people in their families to carry the mutation.
Most children with hereditary neuroblastoma caused by a mutation in the PHOX2B gene did not inherit the mutation from a parent. These children have no history of the condition in their family. In these cases, the gene mutation happened either in:
No matter how they acquired the mutation, people with hereditary neuroblastoma have a 50% (1 in 2) chance of passing it on to their children.
A health care provider may suspect that your child has hereditary neuroblastoma after looking at their medical and family cancer history.
This information helps the health care provider and the genetic counselor know if:
Your provider or genetic counselor may recommend genetic testing if they suspect hereditary neuroblastoma.
Learn more about types of genetic tests.
A blood sample is sent to a genetic testing lab. The lab runs genetic tests that look for changes in the ALK gene, the PHOX2B gene, or both.
If your child has a mutation in the ALK gene or the PHOX2B gene, a genetic counselor will work with your family to:
It is important to remember that genetic testing does not always find mutations in the ALK or PHOX2B genes for all people with hereditary neuroblastoma. A person can still have hereditary neuroblastoma even if no mutations are found in these genes. There may be other genes that are related to the condition that doctors do not know about yet.
Parents may choose to do prenatal testing to find out if a pregnancy is affected with a known ALK or PHOX2B mutation. Testing may take place either before pregnancy occurs or during pregnancy.
You should work with a genetic counselor to review the pros and cons of the test. The genetic counselor can also help you prepare for the results.
Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT tests embryos for a known ALK or PHOX2B mutation before a provider places the embryo into the uterus.
Testing during pregnancy can help providers see if a pregnancy has a known ALK or PHOX2B mutation. A doctor gathers cells from the pregnancy in 1 of 2 ways:
After tissue collection, the lab checks the sample for the ALK or PHOX2B mutation identified in the family. Both tests carry minor risks. Discuss these risks with an experienced health care provider or genetic counselor.
Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.
Sometimes, children or adults with hereditary neuroblastoma feel sad, anxious, or angry after getting their test results. Parents may feel guilty if they pass the ALK or PHOX2B mutation to 1 or more of their children. People with the ALK or PHOX2B mutation may also have trouble getting disability or life insurance.
Read more about genetic discrimination.
Children with hereditary neuroblastoma should have regular screenings to detect tumors as early as possible. The goal of screening is to find and treat tumors early to allow the best outcome for patients.
Neuroblastoma screening is recommended for people who have 1 of the following:
If possible, people with hereditary neuroblastoma should be managed by a health care provider who knows this condition well and who specializes in treating neuroblastoma.
You and your child’s care provider may consider the following tests:
Recommendations may change as we learn more about hereditary neuroblastoma. Parents should discuss all screening options for their child with a health care provider who knows hereditary neuroblastoma well, if possible. Because it is a complex condition, it is important that parents seek out an experienced provider for their child.
People of any age with hereditary neuroblastoma have a higher risk of cancer. They should monitor their health and adopt healthy habits throughout life.
It is important to continue to have regular physical checkups and screenings. That way, any cancer can be found early and at the most treatable stage.
People with hereditary neuroblastoma should watch closely for general signs or symptoms that could signal cancer:
It is important to seek medical help if anything unusual appears.
Habits that will help you maintain a healthy lifestyle include:
The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer and to improve the care and treatment for patients who are affected by these conditions. Learn more about the Division of Cancer Predisposition at St. Jude.
Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:
Hereditary neuroblastoma increases your child’s risk for cancer.
St. Jude offers clinical trials and cancer research studies for children, teens, and young adults who have cancers linked to hereditary neuroblastoma . See diseases treated at St. Jude.
Learn more about clinical research at St. Jude
Study goal:
To learn more about participants beliefs, attitudes, and questions about gene therapy to help make web-based resources to share information. This could help patients make treatment decisions.
Age:
18 to 35 years old with rare genetic diseases
Study goal:
The main goal of this study is to learn more about the reasons childhood tumors form and how to treat them better.
Study goal:
To provide a high-quality repository of tumor and normal samples to facilitate translational research performed by St Jude faculty and their collaborators
Study goal:
1) Test each patient for hundreds of gene variations that might be important for drug use. All of the gene test results will be in the research laboratory, but as time goes on, the study will evaluate scientific evidence and selectively move test results for a few genes into the medical record if the evidence strongly shows that the result can help in better prescribing of drugs for patients; 2) Estimate how often pharmacogenetic test results are moved from research tests into a patient’s medical record; 3) Use methods to choose which of these tests should be put in the medical record; 4) Use computer-based tools in the electronic medical record to help doctors use gene test results when prescribing drugs; 5) Share feelings and concerns of patients and their families about gene test information being put in their medical record.
Study goal:
The main purpose of this trial is to learn about the genetic causes of cancer.
Age:
Younger than 50 years old
Study goal:
To collect data about how Friedreich’s ataxia progresses over time and affects the daily life of patients.
Age:
Any
Patients accepted to St. Jude must have a disease we treat and must be referred by a physician or other qualified medical professional. We accept most patients based on their ability to enroll in an open clinical trial.
Call: 1-888-226-4343 (toll-free) or 901-595-4055 (local) | Fax: 901-595-4011 | Email: referralinfo@stjude.org | 24-hour pager: 1-800-349-4334
If you have questions about the Genetic Predisposition Clinic and care for hereditary neuroblastoma, email our team at GPTeam@stjude.org.