Trochet et al. (2004) reported a family with neuroblastoma. The proband had a multifocal abdominal ganglioneuroma surgically removed at age 10 years. His younger brother presented with an abdominal neuroblastoma at age 6 years, which was surgically removed, ... Trochet et al. (2004) reported a family with neuroblastoma. The proband had a multifocal abdominal ganglioneuroma surgically removed at age 10 years. His younger brother presented with an abdominal neuroblastoma at age 6 years, which was surgically removed, and experienced local recurrences 18 months and 30 months later. The father had a ganglioneuroma of the adrenal medulla, which was surgically removed at age 44 years. An unrelated patient had a diagnosis of Hirschsprung disease (HSCR1; 142623) in the neonatal period and was treated surgically with a good result. Multifocal neuroblastoma tumors, both thoracic and abdominal, were diagnosed at age 9 months and were surgically removed. A 10-year follow-up showed no recurrence. McConville et al. (2006) reported a family with neuroblastoma. The index case, from whom no DNA was available, died at age 5 years with metastatic neuroblastoma and ganglioneuroblastoma. Her father and paternal grandmother both had adult-onset ganglioneuroblastoma. Another paternal relative, from whom DNA was not available, died at age 14 years from ganglioneuroblastoma. None of the family members had Hirschsprung disease or any features of autonomic dysfunction.
Trochet et al. (2004) identified germline mutations in the PHOX2B gene in both a familial case of neuroblastoma (R100L; 603851.0005) and in a patient with sporadic neuroblastoma associated with Hirschsprung disease (R141G; 603851.0006). The latter patient inherited the ... Trochet et al. (2004) identified germline mutations in the PHOX2B gene in both a familial case of neuroblastoma (R100L; 603851.0005) and in a patient with sporadic neuroblastoma associated with Hirschsprung disease (R141G; 603851.0006). The latter patient inherited the mutation from his unaffected mother, suggesting incomplete penetrance. PHOX2B was the first gene in which germline mutations were demonstrated to predispose to neuroblastoma. In 2 affected members of a family with neuroblastoma, McConville et al. (2006) identified a heterozygous mutation in the PHOX2B gene (G197D; 603851.0008). Two unaffected sibs of the index patient's grandmother also carried the mutation, indicating incomplete penetrance. The mutation was located outside of domains typically affected in other PHOX2B syndromes.