University of Oulu

Epidemiological, clinical and genetic aspects of neurofibromatoses in Northern Finland

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Author: Pöyhönen, Minna1,2
Organizations: 1University of Oulu, Faculty of Medicine, Department of Clinical Genetics
2Family Federation of Finland, Department of Medical Genetics
Format: ebook
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
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Language: English
Published: 1999
Publish Date: 1999-10-15
Thesis type: Doctoral Dissertation
Defence Note: Academic Dissertation to be presented with the assent of the Faculty of Medicine, University of Oulu, for public discussion in Auditorium 6 of the University Hospital of Oulu, on November 12th, 1999, at 12 noon.
Reviewer: Docent Jaakko Ignatius
Professor Juha Peltonen


A population-based study to investigate the epidemiological, genetic and clinical features of neurofibromatoses (NF) in Northern Finland was carried out between 1989–1996. The area concerned was that served by Oulu University Hospital, with a total population of 733 037.

A total of 197 patients with neurofibromatosis type 1 (NF1), five with neurofibromatosis type 2 (NF2) and eight with segmental neurofibromatosis (NF5) fulfilling the diagnostic criteria were identified among several hundred patients examined on account of a possible NF diagnosis. The 197 NF1 patients came from 119 families. 77 of these cases were sporadic, 117 familial, and three were mothers of children suffering from NF1 who were themselves diagnosed as having segmental NF. The male/female ratio was 0.93 (95 males and 105 females). The geographical distribution of the patients roughly corresponded to that of the general population in the area. The overall prevalence of NF1 was 23/100 000, with a peak prevalence of 34/100 000 in the age group 10 to 19 years. The overall birth incidence of NF1 was estimated to be 27/100 000, with the highest figure, 37/100 000, recorded in the six-year period 1990–1995. The mean age at the time of diagnosis was 20 ± 16 years in the whole population and 6 ± 4 years in the children born in the 1980’s.

A new mutation was suspected in 49% of the NF1 cases (96/197), and a mutation rate of 4.37 ± 0.72 × 10⁻⁵ was obtained for the period 1960–1995. The relative fitness of the NF1 patients was 0.48, being reduced more in the affected males (0.24) than in the females (0.72). The mean maternal and paternal ages of the sporadic patients were 30 ± 6 and 33 ± 6 years, respectively, which is significantly higher than in the general population. Two cases with a deletion of the NF1 gene were identified, one encompassing the loci from EVI-20 to INT-38 and the other the INT-27 locus, representing 3% of the 66 cases analysed. In seven familial cases the parental origin of the new mutation could be verified and linkage studies showed that the oldest affected individual in the family had inherited the mutation from the father in 6/7 cases.

In one family seven members in three generations were affected with a rare spinal neurofibromatosis, and a linkage to the NF1 gene was shown. Of these seven patients, four are included among the 197 studied here while the other three lived outside the area.

The diagnostic features of the 164 NF1 patients aged from three months to 73 years who were examined clinically included café au lait spots (CLS) in 96% of cases, freckles in 87%, neurofibromas in 69%, plexiform neurofibromas in 20%, Lisch nodules in 70%, optic glioma (asymptomatic) in 20% and pseudarthrosis in 3%. 56% of the cases had an affected first degree relative. A plexiform neurofibroma was diagnosed in 33 individuals and this became a malignant peripheral nerve sheath tumour(MPNST) during the seven years of monitoring in 15% of cases (5/33). Hyperintense T2 lesions in a MRI scan of the brain were found in 94% of the children under the age of six years who had had such a scan (n = 17) and in 84% of those under 16 years (n = 50).

Symptoms related to NF1 which needed medical intervention, rehabilitation or follow-up were diagnosed in about 2/3 of the cases, and in 38% of cases such medical problems of this kind had been treated before NF1 was actually diagnosed. All these findings emphasise the need for a multidisciplinary approach to the follow-up of neurofibromatoses.

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Series: Acta Universitatis Ouluensis. D, Medica
ISSN-E: 1796-2234
ISBN: 951-42-5418-X
ISBN Print: 951-42-5417-1
Issue: 557
Copyright information: © University of Oulu, 1999. This publication is copyrighted. You may download, display and print it for your own personal use. Commercial use is prohibited.