Abdominal tumors in patients with neurofibromatosis type I: Genotype-phenotype relationships

Eur J Med Genet. 2022 Nov;65(11):104609. doi: 10.1016/j.ejmg.2022.104609. Epub 2022 Sep 10.

Abstract

Background: Gastrointestinal stromal tumors have been detected in 25% of the necropsies performed on NF1 patients, but have been reported only in 7% of NF1 patients in the largest series. Such data imply an important gap between the true presence of tumors and those diagnosed. Few genotype-phenotype relationships have been described but to date none referring to abdominal tumors.

Objectives: Evaluate retrospectively the efficacy of a regular and proactive follow-up of NF1 patients to early diagnose abdominal tumors and report their mutations.

Methods: Cohort study performed between 2010 and 2020, with 43 NF1 adult patients followed at our Dermatology department.

Results: Eight abdominal tumors were diagnosed in six patients, meaning that 14% of the followed patients developed an abdominal tumor. Five patients (83%) were asymptomatic. Five (83.3%) had a family history of NF1 with abdominal tumors (patients 1,2 and 3,4,5 were relatives).

Conclusions: Although currently gastrointestinal routine screening investigations for asymptomatic patients are not recommended in the guidelines, the family aggregation in our series suggests it should be considered a close follow-up of the relatives of a patient with an NF1-related abdominal tumor. Also, for the first time, two mutations [c.2041C > T (p.Arg681Ter) and c.4537C > T (p.Arg1513*)] have been associated with family aggregation of abdominal tumors in NF1 patients.

Keywords: Abdominal tumors; Neurofibromatosis type I; Periampullary somatostatin-producing tumors; Pheochromocytoma; gastrointestinal stromal tumors.

MeSH terms

  • Abdominal Neoplasms* / complications
  • Abdominal Neoplasms* / genetics
  • Cohort Studies
  • Genotype
  • Humans
  • Neurofibromatosis 1* / complications
  • Neurofibromatosis 1* / genetics
  • Neurofibromatosis 1* / pathology
  • Phenotype
  • Retrospective Studies