{"id":27154,"date":"2024-05-26T14:40:06","date_gmt":"2024-05-26T12:40:06","guid":{"rendered":"https:\/\/www.krebs-praedisposition.de\/?post_type=kompendium&p=27154"},"modified":"2025-08-26T12:53:15","modified_gmt":"2025-08-26T10:53:15","slug":"phox2b-deficiency","status":"publish","type":"kompendium","link":"https:\/\/www.krebs-praedisposition.de\/en\/kompendium\/phox2b-deficiency\/","title":{"rendered":"PHOX2B Deficiency"},"content":{"rendered":"

PHOX2B Deficiency \u2013\u00a0Definition<\/h2><\/div>
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A heterozygous pathogenic germline variant in the PHOX2B<\/em> gene causes a PHOX2B-related predisposition to neuroblastic tumors (OMIM #603851). It favors the development of neuroblastic tumors (neuroblastomas, ganglioneuroblastomas, and ganglioneuromas), Hirschsprung\u2019s disease, and congenital central hypoventilation syndrome (CCHS).<\/p>\n<\/div>

Synonyms:<\/p>\n<\/div><\/div><\/div>

Sarcoma breast leukemia and adrenal gland cancer syndrome<\/p>\n<\/div><\/div><\/div><\/div>

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Gene:<\/p>\n<\/div><\/div><\/div>

PHOX2B<\/i><\/p>\n<\/div><\/div><\/div><\/div>

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Gen\u00ade product:<\/p>\n<\/div><\/div><\/div>

PHOX2B<\/p>\n<\/div><\/div><\/div><\/div>

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Function:<\/p>\n<\/div><\/div><\/div>

Proliferation regulation of immature sympathetic neurons<\/p>\n<\/div><\/div><\/div><\/div>

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Pattern of inheritance:<\/p>\n<\/div><\/div><\/div>

Autosomal dominant<\/p>\n<\/div><\/div><\/div><\/div>

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Prevalence:<\/p>\n<\/div><\/div><\/div>

Along with pathogenic variant ALK<\/i>, around 1-2% of neuroblastoma patients<\/p>\n<\/div><\/div><\/div><\/div>

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Genotyp-Ph\u00e4notyp-Korrelation:<\/p>\n<\/div><\/div><\/div>

Polyalanine repeat mutations (PARM) in the PHOX2B<\/em> 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).
\nWhile missense, frameshift, and truncating mutations in the PHOX2B<\/em> 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).<\/p>\n<\/div><\/div><\/div><\/div>

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Penetrance:<\/p>\n<\/div><\/div><\/div>

Probably around 50%<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/div>

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Overview of the Chapters on This Page:<\/h4><\/div><\/div><\/div>