Earliest Clinical Manifestations and Natural History of Neurofibromatosis Type 2 (NF2) in Childhood: A Study of 24 Patients

M. Ruggieri; P. Iannetti; A. Polizzi; I. La Mantia; A. Spalice; O. Giliberto; N. Platania; A. L. Gabriele; V. Albanese; L. Pavone

doi:10.1055/s-2005-837581

Neuropediatrics, Table of Contents

Neuropediatrics 2005; 36(1): 21-34
DOI: 10.1055/s-2005-837581

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Earliest Clinical Manifestations and Natural History of Neurofibromatosis Type 2 (NF2) in Childhood: A Study of 24 Patients[*]

M. Ruggieri¹ ^, ² , P. Iannetti³ , A. Polizzi² , I. La Mantia⁴ , A. Spalice³ , O. Giliberto⁵ , N. Platania⁶ , A. L. Gabriele⁷ , V. Albanese⁶ , L. Pavone²

¹Institute of Neurological Science (ISN), National Research Council (CNR), Catania, Italy
²Department of Pediatrics, University of Catania, Catania, Italy
³2nd Chair of Pediatrics, Division of Child Neurology, Department of Pediatrics, University of Rome “La Sapienza”, Rome, Italy
⁴Institute of Otolaryngology, University of Catania, Catania, Italy
⁵Neurosurgery Unit, Cannizzaro Hospital, Catania, Italy
⁶Neurosurgery Unit, Department of Neuroscience, University of Catania, Catania, Italy
⁷Institute of Neurological Science (ISN), National Research Council (CNR), Cosenza, Italy

Abstract

Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterised by the development of multiple nervous system tumours, ocular abnormalities, and skin tumours. Although classically considered a disease of adults, initial signs and/or symptoms may be evident in childhood and are often unrecognised. Objectives: The aim of this study was to identify the earliest clinical presentations of NF2 and to characterise the clinical course and outcome in children with NF2. Methods: We have performed a retrospective (years 1990 - 1998) and prospective (years 1998 - 2004) study of 24 patients (10 males, 14 females; currently aged 4 to 22 years) fulfilling the revised (Manchester) NF2 criteria seen at the Universities of Catania and Rome, Italy. Results: Causes of referral prior to a definitive diagnosis of NF2 were: 1) Ophthalmologic problems: early onset lens opacities (n = 3); strabismus (n = 3) and amblyopia (n = 3) (due to underlying cranial nerves and/or brain tumours); 2) Otolaryngology problems: hearing loss and tinnitus (n = 2) in early teens disregarded or treated as ear infections; hoarse (n = 1) or bitonal (n = 1) voice; 3) Neurological dysfunction: seizures secondary to intracranial meningioma (n = 1) or vestibular schwannomas (VS) (n = 1), neurological dysfunction related to brainstem and/or spinal cord tumours (n = 7), isolated and multiple cranial nerve deficits (n = 10), and peripheral neuropathy secondary to schwannomas (n = 4); 4) Skin manifestations: schwannomas misdiagnosed as neurofibromas because of associated café-au-lait spots (n = 2); café-au-lait spots (n = 8) and skin tumours (n = 3). A family history was relevant in 20 % of the patients. Molecular genetic analysis of the NF2 gene revealed typical truncating mutations in all the 5 familial cases and in 2/10 sporadic cases analysed. Conclusions: Children with NF2 often first come to medical attention because of ocular, subtle skin, or neurological problems the significance of which is realised when they later present with more classical symptoms due to bilateral VS or other intracranial tumours. The clinical course at this young age is highly variable, depending on tumour burden, early surgical intervention, surgical outcome after tumour resection, and complications.

Key words

Neurofibromatosis - NF2 - early onset - paediatric

Full Text

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1 This work was done at the Departments of Pediatrics, University of Catania and Division of Child Neurology, Department of Pediatrics, University of Rome “La Sapienza”, Italy. Presented in part at the 5th European Pediatric Neurology Society (EPNS) Meeting held in Taormina, Italy, 22 - 25 October 2003 (Eur J Pediatr Neurol 2003; 7: 359)

MD, PhD Martino Ruggieri

Institute of Neurological Science (ISN)
National Research Council (CNR)

Viale R. Margherita 6

95125 Catania

Italy

Email: m.ruggieri@isn.cnr.it