Presenting symptoms in children with neurofibromatosis type 2

Isabel Gugel,Christian Teuber,Florian Grimm,Martin Ulrich Schuhmann,Marcos Tatagiba,Victor-Felix Mautner,Julian Zipfel,Lan Kluwe

doi:10.1007/s00381-020-04729-w

Abstract

PurposeThe hallmark of neurofibromatosis type 2 (NF2) is the presence of bilateral vestibular schwannomas (VS) which however have not yet developed or grown to large size in children and young adolescents. Therefore, early diagnosis in pediatric patients without family history of NF2 has to be made by signs and symptoms not related to VS which will be reviewed in this study.MethodsA total of 70 children diagnosed for NF2 at an age of < 18 years were identified from our patient cohort. Age and symptoms, signs and pathology at symptom onset, age at NF2 diagnosis and symptoms leading to diagnosis as well as genetic findings were retrospectively reviewed.ResultsThe average age at symptom/sign onset was 8 ± 6 (range 0–17) years and 11 ± 5 (range 1–17) years at time of diagnosis. Fifteen children had a positive family history and were diagnosed upon additional clinical symptoms. The most frequent first presenting symptom/signs were ophthalmological abnormalities (49%), followed by cutaneous features (40%), non-VS-related neurological deficits (33%), and symptoms attributable to VS (21%). VS were not only the most common symptomatic neoplasm but also the most frequent pathological evidence for the diagnosis (72%). In 42 patients with available genetic testing results, pathogenic mutations were most frequently identified (n = 27).ConclusionThe presenting symptoms in NF2 children appear “unspecific” or less specific for classical NF2 compared with adult NF2 patients, posing a challenge particularly for cases without family history. In children, ophthalmological and cutaneous features should raise clinical suspicion for NF2 and referral to an NF2 specialized center is recommended.

Highlights

The genetic tumor predisposition syndrome neurofibromatosis type 2 (NF2) is a rare disease with a prevalence of 1:56.000 and an incidence of 1 case in 33,000 to 40,000Department of Neurosurgery, University Hospital Tübingen, Tübingen, GermanyCentre of Neurofibromatosis, Centre of Rare Disease, University Hospital Tübingen, Tübingen, GermanyDivision of Pediatric Neurosurgery, University Hospital Tübingen, Tübingen, GermanyDepartment of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany live births per year [1, 2]
The typical hallmark of the disease which secures the diagnosis is bilateral vestibular schwannomas (VS) causing tinnitus, balance disorders, dizziness, and later hearing loss and facial palsy depending on tumor size [5]
We retrospectively reviewed our NF2 cohort diagnosed at age younger than 18 years, focusing on the variety of very first symptoms which initialized further examination resulting in the final diagnosis of NF2

Summary

Introduction

The genetic tumor predisposition syndrome neurofibromatosis type 2 (NF2) is a rare disease with a prevalence of 1:56.000 and an incidence of 1 case in 33,000 to 40,000Division of Pediatric Neurosurgery, University Hospital Tübingen, Tübingen, Germany. Early diagnosis with ensuing early awareness of VS and monitoring of hearing is crucial

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Conclusion