Neurofibromatosis type 1 adult surveillance form for Austria

Abstract

Background: Neurofibromatosis type 1 (NF1) is a rare autosomal dominant tumor predisposition syndrome with a birth prevalence of approximately 1 in 2000-3000 individuals. Management of both benign and malignant tumors arising in individuals with NF1 is demanding and tumors may be difficult to treat. Both standardized and individual surveillance programs are therefore highly important to prevent morbidity and mortality in patients with NF1.

Methods: The guidelines for the clinical management of NF1 recently proposed by the European Reference Network for Genetic Tumor Risk Syndromes provide the cornerstone of the present surveillance form and were discussed through three rounds of voting and a final consensus meeting involving experts from five Austrian and one German clinical NF1 centers for adults and one patient organization representative. Subsequently, 31 items within 4 categories were integrated into the proposed surveillance form for Austria. All recommendations, unless otherwise specified, pertain to primarily asymptomatic patients in routine follow-up.

Recommendations: At healthcare transition from pediatric to adult surveillance or the initial visit in adulthood, we suggest a thorough clinical, laboratory and radiological examination to obtain a baseline for future diagnostics. To comply with the general screening recommendations in Austria, we suggest extending the frequency of clinical visits from annual to biennial at 50 years of age. In cases of clinical dynamics, early follow-up is recommended to facilitate early detection of potential complications. Particular emphasis should be placed on preventive patient education.

Keywords: Cancer; Neurofibromatosis type 1; Prevention; Screening; Tumor predisposition syndromes.

Fig. 1

Manifestations of neurofibromatosis type 1. ADHD attention deficit hyperactivity disorder, GIST gastrointestinal stromal tumor, JMML juvenile myelomonocytic leukemia, MPNST malignant peripheral nerve sheath tumor

Fig. 2

The Neurofibromatosis Type 1 Adult Surveillance Form for Austria ¹ Signs suggestive of MPNST: rapidly growing or painful nodules, new neurological deficits, changes in consistency (e.g., new nodule in soft neurofibroma). ² Signs suggestive of a CNS tumor: New focal neurological symptoms, de novo continuous headache, epileptic seizures, neurocognitive changes. ³ Signs suggestive of GIST: changes in digestion continuous abdominal pain, unintentional weight loss. ⁴ If not previously performed. ⁵ High-risk patient for MPNST development if 1 of the following criteria is met: previous atypical neurofibroma (ANNUBP); high internal tumor load; large or multiple plexiform neurofibromas; history of radiotherapy; a relative with NF1 and MPNST; NF1 microdeletion (including SUZ 12) or missense variant affecting codons 844–848. ⁶ In complex cases, unclear imaging, high-risk constellations. ANNUBP atypical neurofibromatous neoplasm of uncertain biological potential, CNS central nervous system, CT computed tomography, EEG electroencephalography, EKG electrocardiography, FDG-PET fluorodeoxyglucose positron emission tomography, GIST gastrointestinal stromal tumour, MPNST malignant peripheral nerve sheath tumor, MRI magnetic resonance imaging, NF neurofibromatosis, OCT optical coherence tomography

Fig. 3

Austrian clinical centers and patient organization involved in the iterative consensus making process for the NF1 Adult Surveillance Form for Austria