2025 Proffered Presentations
S287: DIFFERENCES IN DISEASE PRESENTATION AND RATES OF POSITIVE GENETIC TESTING BETWEEN PATIENTS DIAGNOSED WITH NF2-RELATED SCHWANNOMATOSIS BEFORE AND AFTER 30 YEARS OF AGE
Brennan Olson, MD, PhD; Matthew Carlson, MD; Brian Neff, MD; Colin Driscoll, MD; Dusica Babovic-Vuksanovic, MD; Lisa A Schimmenti, MD; James Dornhoffer, MD; Mayo Clinic
Background: NF2- related schwannomatosis (NF2) is a rare genetic disorder with a broad phenotypic profile. Prior work suggests diagnosis at a younger age portends a worse prognosis, although limited data exists for patients diagnosed well into adulthood. Furthermore, rates of genetic testing, positive genetic testing results, including mosaicism and association with disease severity among patients diagnosed in adulthood is less studied. Herein, we sought to characterize pathogenic variants, rates of mosaicism, genetic testing yield, and disease severity amongst NF2 patients dichotomized by diagnosis before or after the age of 30.
Methods: A retrospective chart review was performed at a tertiary medical center for patients evaluated at the Mayo Clinic Multidisciplinary NF2 Clinic from 2021 to 2024. We dichotomized patients by age greater than (N=32) and less than 30 (N=39). Between these two cohorts, we analyzed and compared rates of mosaicism, genetic testing rates and yield, and overall disease severity via tumor burden by Chi-Square test or two-tailed t-test.
Results: Patients diagnosed with NF2 after the age of 30 exhibited higher likelihood of no family history of disease (88% vs. 79%; p = 0.17), decreased likelihood of receiving genetic testing (53% vs. 85%; p = 0.009), and decreased genetic yield (defined as identification of a pathogenic genetic variant in those undergoing testing; 65% vs. 85%; p = 0.20) compared to the NF2 patients diagnosed before the age of 30. Of the patients who received positive genetic testing results, only 1 patient in the <30 age group had LZTR1 related schwannomatosis. Both age groups demonstrated similar rates of pathogenic variant type with loss-of-function (LOF) being the predominant variant detected (>30 age group, 73% vs. <30 age group 67%; p = 0.90). The >30 age group exhibited fewer number of average anatomic regions involved by tumor (1.3 vs 2.4; p < 0.001) and decreased total number of tumors (7 vs. 12; p < 0.001) compared to the <30 age group. When comparing mosaic to non-mosaic variants in the >30 age group, individuals who had mosaic results trended towards increased number of compartments involved (1.8 vs. 1.2; p = 0.18) and total tumor burden (7.7 vs 5.7; p = .0.29), although these were not statistically significant, and thus, should be considered similar.
Conclusions: Herein, we report the rates of completed genetic testing, incidence of mosaicism, and disease severity amongst patients clinically diagnosed with schwannomatosis at a large multidisciplinary NF2 clinic. Our study identified a lower rate of completed genetic testing and testing yield in patients diagnosed with NF2 after the age of 30 compared to their younger counterparts. Consistent with prior studies, our data demonstrate an increased disease burden among younger NF2 patients compared to the older cohort. However, individuals identified to be mosaic and diagnosed at a later age exhibited similar disease burden defined by the number of anatomic compartments involved and overall tumor burden compared to their non-mosaic counterparts, challenging the broader notion that individuals who are mosaic for NF2 pathogenic variants tend to have a milder form of the disease.
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