Definition
A PHOX2B-related predisposition to neuroblastic tumors (OMIM #603851) is caused by a heterozygous germline mutation in the PHOX2B gene and favors the development of neuroblastic tumors (neuroblastomas, ganglioneuroblastomas, and ganglioneuromas), Hirschsprung’s disease, and congenital central hypoventilation syndrome (CCHS).
Key Data
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Synonyms | Sarcoma breast leukemia and adrenal gland cancer syndrome |
Gene | PHOX2B |
Gene product | PHOX2B |
Function | Proliferation regulation of immature sympathetic neurons |
Heredity | Autosomal dominant |
Prevalence | Along with ALK mutations, around 1-2% of neuroblastoma patients |
Genotype-phenotype correlation | Polyalanine repeat mutations (PARM) in the PHOX2B gene are associated with more severe cases of hypoventilation with CCHS (the longer the polyalanine tract expansion, the more pronounced the hypoventilation) and with neuroblastic tumors (neuroblastomas, ganglioneuroblastomas, and ganglioneuromas).
While missense, frameshift, and truncating mutations in the PHOX2B gene (non-polyalanine repeat mutations, NPARM) are much rarer, they are nevertheless associated with a much higher risk of developing neuroblastic tumors (around 45% compared to 1-2% with PARM). |
Penetranz | Probably around 50% |
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Diagnosis
Clinical Diagnostics
A PHOX2B-related predisposition to neuroblastic tumors is suspected with the following findings:
Genetic Diagnostics
The diagnosis of a “PHOX2B-related predisposition to neuroblastic tumors” is confirmed by the detection of a heterozygous germline mutation in the PHOX2B gene.
Differential Diagnoses
Clinical Presentation
Patients with a PHOX2B-related predisposition for neuroblastic tumors (especially NPARM) have an increased risk of developing neuroblastic tumors, such as the following:
In addition, there is also an increased risk of developing neurocristopathies, particularly CCHS and Hirschsprung’s disease. In patients with CCHS, the risk of developing a neuroblastic tumor is around 5-10%.
A few patients with a PHOX2B mutation exhibit facial dysmorphia, such as drooping palpebral fissures, a narrow nose, a triangular mouth, or low-lying ears that are rotated towards the back.
Therapeutic Considerations
Treatment is in accordance with the treatment guidelines of the neuroblastoma study.
Surveillance Recommendations
Surveillance Recommendations
There are no standard recommendations to date. The following is a possible approach for the early detection of neuroblastic tumors when a PHOX2B mutation has been detected:
Clinical examination, ultrasound of the abdomen, measurement of the catecholamines, VMA, and HVA in the urine, X-ray of the thorax (PA and lateral)
Additional Information
Open Clinical Trials / Registries
Support Groups
Unfortunately, we are as yet unaware of any existing support groups for patients with a PHOX2B-related predisposition to neuroblastic tumors. We will add new information as it becomes available.