Neuropediatrics 2013; 44(05): 239-244
DOI: 10.1055/s-0033-1343350
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Spinal Neurofibromatosis with Central Nervous System Involvement in a Set of Twin Girls and a Boy: Further Expansion of the Phenotype

Martino Ruggieri
1  Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy
2  Unit of Neurosurgery, Department of Neurosciences, University of Catania, Catania, Italy
,
Agata Polizzi
3  National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy
4  Institute of Neurological Sciences, National Research Council, Catania, Italy
,
Vincenzo Salpietro
5  Unit of Genetics and Paediatric Immunology, Department of Pediatrics, University of Messina, Messina, Italy
,
Gemma Incorpora
6  Unit of Pediatrics, ARNAS Hospital “Garibaldi,” Catania, Italy
,
Francesco Nicita
7  Division of Child Neurology, Department of Pediatrics, University of Rome “La Sapienza,” Rome, Italy
,
Piero Pavone
8  Unit of Pediatrics “Costanza Gravina,” University Hospital “Policlinico-Vittorio Emanuele,” Catania, Italy
,
Raffaele Falsaperla
8  Unit of Pediatrics “Costanza Gravina,” University Hospital “Policlinico-Vittorio Emanuele,” Catania, Italy
,
Caterina Nucifora
9  Unit of Pediatrics and Neonatology, Civic Hospital, Siracusa, Italy
,
Francesca Granata
10  Unit of Neuroradiology, University of Messina, Messina, Italy
,
Angela Distefano
11  Unit of Nuclear Medicine, Institute of Neurological Sciences, National Research Council, Catania, Italy
,
Luca Padua
12  Unit of Clinical Neurophysiology, Catholic University of Sacred Heart, Rome, Italy
,
Rosario Caltabiano
13  Department “G.F. Ingrassia,” Section of Anatomic Pathology, University of Catania, Catania, Italy
,
Salvatore Lanzafame
13  Department “G.F. Ingrassia,” Section of Anatomic Pathology, University of Catania, Catania, Italy
,
Anna Lia Gabriele
14  Unit of Molecular Genetics, Institutes for Mediterranean Agriculture and Forest Systems (ISAFOM), National Research Council (CNR), Renda (CS), Italy
,
Andrea Ortensi
15  Unit of General Microsurgery and Hand Surgery, University of Rome “La Sapienza” and Hospital “Fabia Mater,” Rome, Italy
,
Valerio D'Orazi
15  Unit of General Microsurgery and Hand Surgery, University of Rome “La Sapienza” and Hospital “Fabia Mater,” Rome, Italy
,
Andrea Panunzi
15  Unit of General Microsurgery and Hand Surgery, University of Rome “La Sapienza” and Hospital “Fabia Mater,” Rome, Italy
,
Pietro Milone
16  Unit of Neuroradiology, Institute of Radiology, University of Catania, Catania, Italy
,
Kshitij Mankad
17  Unit of Pediatric Neuroradiology, Great Ormond Street Hospital, London, United Kingdom
,
Nunzio Platania
2  Unit of Neurosurgery, Department of Neurosciences, University of Catania, Catania, Italy
,
Vincenzo Albanese
2  Unit of Neurosurgery, Department of Neurosciences, University of Catania, Catania, Italy
,
Vito Pavone
18  Institute of Orthopaedics, University Hospital “Policlinico-Vittorio Emanuele,” Catania, Italy
› Author Affiliations
Further Information

Publication History

12 December 2011

18 February 2013

Publication Date:
18 June 2013 (online)

Abstract

Background Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations.

Objectives The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature.

Methods and Results In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1–like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature.

Conclusions This article presents the first report on (1) spinal neurofibromatosis in a set of affected monozygotic twins; (2) the earliest onset of the disease; and (3) the occurrence of high signal lesions in the brain at MRI.