"PHOX2B Deficiency" – What Is It?
The PHOX2B-related predisposition to neuroblastic tumors is based on a genetic alteration in the PHOX2B gene. It indicates an increased probability of developing tumors that arise from autonomic, i.e., not consciously controllable, nerve tissue. These tumors are neuroblastomas, ganglioneuroblastomas and ganglioneuromas. There is also an increased risk of developing Hirschsprung’s disease and congenital central hypoventilation syndrome (CCHS). The terms Hirschsprung’s disease and CCHS are explained below.
How Is "PHOX2B Deficiency" Diagnosed?
Clinical Diagnostics
The presence of a PHOX2B-related predisposition to neuroblastic tumors is suspected in an individual who has any of the following findings:
- Multiple neuroblastic tumors occurring at the same time or at different times
- Occurrence of a neuroblastoma, ganglioneuroblastoma, or ganglioneuroma in more than one family member
- Occurrence of a neuroblastic tumor in combination with CCHS or Hirschsprung’s disease (see below)
Genetic Diagnostics
The diagnosis of “PHOX2B-related predisposition to neuroblastic tumors” is confirmed by the detection of a mutation, i.e., a genetic change in the PHOX2B gene.
Further Clinical Diagnostics
Patients with a PHOX2B-related predisposition to neuroblastic tumors have an increased risk of developing neuroblastic tumors. These are as follows:
- Neuroblastoma: This is a malignant tumor that originates in autonomic, i.e., not consciously controllable, nerve tissue and has the worst outcome of the tumors described here. Neuroblastomas can occur in the spinal column, in the head and neck area, and in the chest, abdomen, and pelvis along the autonomic nerve pathways or on accumulations of autonomic nerve cells. The symptoms vary greatly depending on the location and range from pain, shortness of breath, urinary tract and bowel problems to paralysis.
- Ganglioneuroblastoma: These tumors can be either benign, like ganglioneuromas, or malignant, like neuroblastomas. They are usually localized in the trunk’s spinal column and posterior thoracic region.
- Ganglioneuroma: This is a primarily benign tumor that originates from autonomic, i.e., not consciously controllable, nerve tissue. Ganglioneuromas mainly occur in the spine, chest, head, and neck area and on the adrenal glands. These tumors often remain asymptomatic, but they can also cause pain or breathing difficulties.
There is also an increased risk of developing congenital central hypoventilation syndrome (CCHS). This congenital disease of the nervous system is associated with impaired or absent control of autonomic breathing, which is usually more pronounced during sleep than when awake.
Another disease that occurs with PHOX2B mutations is Hirschsprung’s disease, also known as congenital megacolon. Here, the lack of nerve supply to parts of the large intestine leads to a narrowing of a section, resulting in considerable constipation. The resulting fecal blockage leads to an expansion of the section of the intestine that lies above the constriction, resulting in flatulence and vomiting.
Some patients with a PHOX2B mutation also have facial abnormalities such as sloping palpebral fissures, a narrow nose, a triangular-shaped mouth, or low-set, backward-rotated ears.
What Is the Risk of Cancer?
If a patient has a mutation, i.e., genetic change, in the PHOX2B gene, the probability of developing a neuroblastic tumor depends on the type of underlying mutation. In the case of so-called non-polyalanine repeat mutations, the risk is around 50%, whereas it is significantly lower for polyalanine repeat mutations. Discuss this topic during genetic counseling.
What Is Known About the Development of "PHOX2B Deficiency"?
The PHOX2B-related predisposition to neuroblastic tumors is based on a mutation, i.e., a genetic change in the PHOX2B gene. This gene codes for the PHOX2B protein, which controls the proliferation and development of immature nerve cells. If the gene is present in an altered form, the protein is no longer produced correctly and cannot perform its function properly, leading to the development of tumors.
Is There Any Form of Treatment Available?
Patients with PHOX2B-related neuroblastic tumors should be treated in a pediatric oncology clinic. Here, the procedure is also coordinated with the neuroblastoma study management.
Diagnosis of " PHOX2B Deficiency" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " PHOX2B Deficiency" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
To date, there are no uniform recommendations. A possible procedure for the early detection of neuroblastic tumors with a known PHOX2B mutation is as follows:
Clinical examination, ultrasound of the abdomen, measurement of catecholamines (messenger substances of the autonomic nervous system) vanillin mandelic acid, and homovanillic acid in the urine, X-ray of the lungs
- Every 3 months for children aged 0-6 years
- Every 6 months for children aged 6-10 years
- No screening is required for children >10 years of age
PHOX2B Deficiency- What You Can Do Yourself
You Should Pay Attention to This
In congenital central hypoventilation syndrome (CCHS) and Hirschsprung’s disease, symptoms occur immediately or in the first few days after birth. In the case of CCHS, these are disturbed breathing, which usually occurs more frequently during sleep, and in Hirschsprung’s disease, a lack of meconium discharge (the child’s vomit), stool irregularities, or vomiting. A pediatrician should be consulted for both problems.
Suppose other symptoms, complaints, or abnormalities occur in addition to one of the diseases mentioned above or in the case of a known PHOX2B mutation. In that case, you should also consult a doctor to clarify whether a neuroblastic tumor is present.
Further Information
Unfortunately, we are not yet aware of any support groups for patients with PHOX2B-related predisposition to neuroblastic tumors. As soon as we have new information, we will add it here. However, patients can also register for the CPS registry at any time or have this done by their doctors in charge.
Any further questions?
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