I will discuss the epidemiology of schwannomatosis and genotype phenotype correlations of NF2-SWN as well as the rates of mosaicism. The proportion of non-NF2 SWN due to LZTR1 and SMARCB1 as well as rare other causes.

Background: Schwannomatosis (SWN) is a group of genetic syndromes with a predisposition to develop schwannomas. In retrospective studies, chronic pain is reported by 70% of patients with non-NF2-related SWN (non-NF2-SWN). While pain is a cardinal symptom of this condition, the trajectory of pain over time is unknown, making prognostication difficult.

Methods: We conducted a prospective, international, multicenter study of English-speaking adults with non-NF2-SWN. Participants received electronic surveys every 6 months for up to 8 years, which included demographics, clinical history, pain intensity (Numerical Rating Scale (NRS-11)), pain classification as nociceptive/neuropathic (ID-Pain), a pain self-efficacy questionnaire (PSEQ-2), and Patient-Reported Outcomes Measurement Information System (PROMIS) Surveys on pain interference, physical functioning, depression, and anxiety.

Results: 79 patients completed baseline surveys with 78.5% reporting chronic pain and a mean pain intensity of 5/10. Increased pain intensity correlated with a history of chronic pain, depression, and number of surgeries, but not age or sex. For the overall cohort, pain intensity, pain interference, depression, and anxiety did not change over multiple years of follow-up, though physical functioning decreased slightly. Unbiased hierarchical clustering identified 4 distinct pain phenotypes based on pain trajectories: persistent severe pain, persistent minimal pain, partially improving moderate pain, and inverted U-trajectory pain.

Conclusions: Evaluation of the largest prospective international cohort of patients with non-NF2-SWN showed no consistent improvement or worsening of pain phenotype during long-term follow-up, despite medical management. The identification of subgroups with distinct pain trajectories requires confirmation but suggests a target population for clinical trials.

Background: NF2-related schwannomatosis (NF2-SWN) is rare in childhood and may present without vestibular symptoms, delaying diagnosis. We characterised presenting features, diagnostic timing, tumour distribution and genetic findings in a large paediatric cohort.

Methods: We performed a retrospective review of symptomatic patients managed through the English national specialist NF2service. Eligible patients had symptom onset before 16 years and met clinical or genetic diagnostic criteria for NF2-SWN. Data were collected on age at first symptom, presenting features, diagnostic interval, tumour spectrum and genetic findings.

Results: In total, 275 patients were included. Mean age at first symptom was 9.3 years and mean diagnostic delay was 6.8 years. The most frequent initial symptoms were hearing loss (23.6%), visual impairment (17.5%) and focal neurological deficits including weakness (17.5%). Presenting features varied by age. Visual loss predominated in children aged under 5 years, cutaneous tumours were the most frequent initial feature in those aged 6 to 10 years, and hearing loss was the commonest initial symptom in those aged 11 to 16 years. Bilateral vestibular schwannomas were present in 234 patients (85%). Genetic testing identified truncating pathogenic variants as the most common variant class (52.7%); mosaicism was more frequent in later-diagnosed cases.

Conclusion: Paediatric NF2-SWN frequently presents with non-vestibular symptoms, causing substantial diagnostic delay. Visual impairment, cutaneous tumours and focal neurological deficits should prompt consideration of NF2-SWN in children, even before hearing loss or bilateral vestibular schwannomas are apparent.

Background: Individuals with NF2-related schwannomatosis (NF2-SWN) experience an array of physical, emotional, and social symptoms that substantially impact their quality of life (QoL). Although disease-specific patient-reported outcome measures are increasingly important for evaluating treatment benefit in clinical trials, existing NF2-SWN QoL measures have limitations in content coverage and sensitivity to change. As such, we developed and initially validated a new disease-specific QoL assessment - the Quality of Life Evaluation in NF2-related Schwannomatosis Trials (QUEST).
Methods: Items were generated through concept elicitation interviews with individuals with NF2-SWN and clinicians, prioritized via patient survey, and refined through iterative cognitive debriefing. The final 21-item QUEST assesses the extent to which NF2-SWN has negatively impacted a person’s daily life over the past seven days. Initial psychometric evaluation was conducted via cross-sectional survey with follow-up at two weeks.
Results: 174 individuals with NF2-SWN aged ≥15 years from the United States, United Kingdom, Canada, and Australia completed the survey. The QUEST total score demonstrated excellent internal consistency (Cronbach’s alpha = 0.95) and test–retest reliability (r=.91). Construct validity was demonstrated through significant correlations in the expected direction and magnitude with other NF2-SWN clinical trial outcome measures [NFTI-QOL (r = .86), Self-Assessment of Communication (r = .54), Functional Assessment of Cancer Therapy-General (r = -.43).] The measure distinguished patients based on self-reported disease severity and number of prior NF2-related surgeries (p<0.001 for both), establishing known-groups validity.
Conclusions: The QUEST is a reliable and valid disease-specific QoL measure with strong content validity and feasibility for use as a clinical trial endpoint in NF2-SWN.

Background: Auditory brainstem implantation (ABI) is the treatment of choice for patients with severe-to-profound sensorineural hearing loss who are not candidates for cochlear implantation, most commonly those with neurofibromatosis type 2 (NF2). We report our institutional experience with ABI and postoperative hearing outcomes.

Methods: We performed a retrospective review of all patients who underwent ABI at our tertiary referral center between January 2012 and December 2023. Demographic data, indications, audiological outcomes, and postoperative complications were analyzed. Hearing outcomes were assessed using pure-tone audiometry and four-frequency pure-tone average (4-PTA).

Results: Eight patients (median age 41 years; 87.5% male) underwent ABI. NF2 was the indication in six patients (75%). Significant postoperative improvements in hearing thresholds were observed at 250 Hz (p=0.042) and 4 kHz (p=0.034), whereas changes at 500 Hz and 1 kHz were not statistically significant. Median preoperative ipsilateral 4-PTA was 86 dB and improved to 67.5 dB postoperatively, although this did not reach statistical significance (p=0.078). Postoperative 4-PTA was comparable between tumor and non-tumor patients (67.5 vs. 74.4 dB; p=0.70). Facial nerve dysfunction occurred in four patients, with partial recovery in one.

Conclusion: ABI provides a valuable hearing rehabilitation option for patients unsuitable for cochlear implantation, particularly those with NF2. Although audiological outcomes remain variable, meaningful hearing improvement can be achieved in selected patients, supporting ABI as an important component of multidisciplinary NF2 management.