Neuroblastoma is a cancer of the sympathetic nerve cells. It mainly affects children before the age of 5 and rarely occurs in adults. A neuroblastoma develops when young nerve cells called neuroblasts grow uncontrollably to form a cancer. Most of the time, neuroblastomas begin in the nerve tissue of the adrenal glands. These glands are small, hormone-producing organs on top of each kidney. Hormones are chemicals that are important for sending messages in the body. Sometimes neuroblastomas begin in the sympathetic nerve cells of the abdomen, chest, neck, or pelvis.
Neuroblastoma most often occurs in children who have no family history of the disease. This is called sporadic neuroblastoma. However, in 1–2% of cases, an increased chance of developing neuroblastoma can be inherited from a parent. This is called Hereditary Neuroblastoma. Children with Hereditary Neuroblastoma are more likely to have a higher number of tumors and to be diagnosed at a younger age than people with sporadic neuroblastoma.
Hereditary Neuroblastoma often varies in how severe it is, even among people in the same family. Some people may have many tumors, while others do not even develop one tumor. Even within the same person with the condition, some tumors might shrink and go away on their own, while other tumors are more aggressive and continue to grow.
Hereditary Neuroblastoma is caused by changes in one of two genes: ALK or PHOX2B.
Genes carry information telling cells in the body how to work. Most people without Hereditary Neuroblastoma carry two working copies of these genes in their cells. One copy is inherited from each parent. Due to changes in the gene ALK or PHOX2B, cells from people with Hereditary Neuroblastoma carry one working copy of that gene and one copy that is changed. This change causes the gene to not work right. It is called a variant. Among people with Hereditary Neuroblastoma, variants in the ALK gene are thought to be the most common.
Most children with Hereditary Neuroblastoma caused by a variant in the ALK gene have inherited the variant from a parent. However, some children with ALK gene variants are the first people in their families to carry the variant.
Most children with Hereditary Neuroblastoma caused by a variant in the PHOX2B gene did not inherit the variant from a parent. These children have no history of the condition in their families. In these cases, the change either happened in an egg or sperm cell when the child was formed or in one of the child’s cells during pregnancy. These children are the first in their families to have hereditary neuroblastoma related to PHOX2B.
Neuroblastoma can also occur in people with Beckwith-Wiedemann Syndrome (due to variants in CDKN1C), Costello Syndrome (due to variants in HRAS), and Weaver Syndrome (due to variants in EZH2). It can occur in people with some other hereditary cancer syndromes, too.
No matter how they acquired the variant, people with Hereditary Neuroblastoma have a 50% (1 in 2) chance of passing it on to their children.
A doctor may suspect this diagnosis after looking at a person’s medical or family history. In most cases, a doctor or genetic counselor will ask questions about the person’s health and the health of other family members. Read more about genetic counseling and genetic testing.
Diagnosing this syndrome is usually done by sequencing the ALK, PHOX2B, CDKN1C, HRAS, and/or EZH2 gene(s) to find variants (changes in the genes).
Genetic testing does not always find a variant responsible for the syndrome. A person can still have the syndrome even if no variants in these genes are found. There are likely to be more, undiscovered genes that play a role in the development of this syndrome.
People with changes in ALK, or certain changes in PHOX2B, are at increased risk to develop tumors, including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. The risk is highest in infancy and decreases by late childhood.
The risk of neuroblastoma in people with ALK variants is estimated to be around 50%.
The risk of neuroblastoma in people with PHOX2B is not currently known, but there is a higher risk of neuroblastoma with certain types of variants, called long (>28) polyamine repeat mutations (PARMS) or non-PARM variants.
Cancer screening involves tests to check for cancer before symptoms occur. The goal is to find cancer at the earliest and most treatable stage. Guidelines for cancer screening are available online. Recommended screenings may change over time as doctors learn more about this syndrome, so these screening tests should be discussed with a health care provider who knows this syndrome well.
Other ideas to reduce the risk of cancer include:
- Eat a healthful diet with lots of fruits and vegetables
- Get regular exercise
- Avoid smoking or using tobacco products
- Avoid secondhand smoke
- Avoid excess sun exposure and always wear sunscreen, hat, and protective clothing when out in the sun
- Get medical attention for unusual or ongoing symptoms
People with PHOX2B variants often have other conditions affecting the nervous system, including:
- Hirschsprung disease, a condition affecting the large intestine (colon) in which some nerves are missing. This results in bowel blockage or trouble passing bowel movements.
- Decreased esophageal motility, a condition affecting the esophagus, the tube that connects the mouth and the stomach. In this condition, the transfer of food from the mouth to the stomach does not work as well as it should.
- Congenital central hypoventilation syndrome, a condition of the central nervous system in which breathing control is absent or not working properly.
These neurological conditions are not seen in people with ALK variants.
Because of the medical concerns related to PHOX2B variants, specialists in the following areas may need to assess a child with Hereditary Neuroblastoma:
- Pulmonology (Sleep specialists)
- Gastroenterology
Resources about Hereditary Neuroblastoma:
- The Neuroblastoma Children’s Cancer Society (www.neuroblastomacancer.org)
- Children’s Neuroblastoma Cancer Foundation (www.cncfhope.org)
- American Cancer Society – Neuroblastoma (www.cancer.org/cancer/neuroblastoma/)
Other resources:
- Making Sense of Your Genes: A Guide to Genetic Counseling (ncbi.nlm.nih.gov/books/NBK115508/)
Adapted from educational materials developed by the St. Jude Children’s Research Hospital Cancer Predisposition Program