Choroidal abnormalities and mental retardation in neurofibromatosis type 1

Abstract

The findings of Takaharu Yasunari and colleagues (Sept 16, p 988)1Yasunari T Shiraki K Hattori H Miki T Frequency of choroidal abnormalities in neurofibromatosis type 1.Lancet. 2000; 356: 988-992Summary Full Text Full Text PDF PubMed Scopus (88) Google Scholar are of utmost clinical importance for the neurofibromatoses, since they highlight the potential importance of choroidal involvement as a new diagnostic criterion for neurofibromatosis type 1 (NF1). However, their conclusion that infrared light examination might be useful for diagnosis in patients with mental retardation and in infants could lend itself to misinterpretation. Such examination could allow diagnosis of NF1 in younger patients who meet only one of the existing NF1 diagnostic critera,2National Institutes of Health Consensus DevelopmentNeurofibromatosis: conference statement.Arch Neurol. 1988; 45: 575-578Crossref PubMed Scopus (1933) Google Scholar but it is unclear whether Yasunari and colleagues propose its use as a screening technique for NF1 in mentally retarded individuals in the general population or just as a (easy and non-invasive) useful diagnostic tool in mentally retarded patients suspected of having NF1 who do not meet the NF1 criteria.2National Institutes of Health Consensus DevelopmentNeurofibromatosis: conference statement.Arch Neurol. 1988; 45: 575-578Crossref PubMed Scopus (1933) Google Scholar The former notion could be misleading in that it apparently stands on the old assumption that NF1 is a mental retardation disorder. In the past, rates of NF1 severe neurological impairment have been reported as high. This assumption generated the idea that every neurological occurrence in a patient with NF1, including mental retardation, was part of the NF1 phenotype. Those rates, however, probably arose because of a bias in ascertaining severely affected patients in old hospital-based series.3Huson SM Hughes RAC The neurofibromatoses: pathogenic and clinical overview. Chapman and Hall, London1994Google Scholar Later population-based studies have shown that the incidence of true mental retardation in NF1 is lower than expected—3·2% in the study of S Huson and colleagues3Huson SM Hughes RAC The neurofibromatoses: pathogenic and clinical overview. Chapman and Hall, London1994Google Scholar (based on retrospective analysis of educational needs) compared with the prevalence of mental retardation (defined as an IQ<70) in the general population (5%).4Opitz JM Vision and insight in the search for gene mutations causing nonsyndromal mental deficiency.Neurology. 2000; 55: 328-330Crossref PubMed Scopus (1) Google Scholar Research on the cognitive phenotype of NF13Huson SM Hughes RAC The neurofibromatoses: pathogenic and clinical overview. Chapman and Hall, London1994Google Scholar, 5North K Cognitive function and academic performance.in: Friedman J Gutmann DH MacCollin M Riccardi VM Neurofibromatosis: phenotype, natural history and pathogenesis. 3rd edn. Johns Hopkins University Press, Baltimore1999: 162-189Google Scholar have established that most NF1 patients have a mean full-scale intelligence quotient (IQ) in the low to average range (around 90) compared with age-matched or sibling controls, but that their risk of frank mental retardation is low. Intellectual impairment in NF1 presents as learning difficulties and is relatively mild and non-progressive. The situation is compounded in around 40% of patients by impairment of gross and fine coordination. The recorded prevalence of mental retardation (by means of neuropsychological testing) in our paediatric NF1 population (338 children, aged 2–17 years, studied at our institution in 1990–99) was similar (3·2%) to that in the general paediatric population. None had profound mental retardation (IQ 20–35). 70% of these mentally retarded NF1 children had a more severe NF1 phenotype, including earlier appearance of an unusually large number of discrete dermal neurofibromas, dysmorphic features, seizures, autism, and central nervous system malformations, and carried large deletions of the NF1 gene (unreported data). Whatever rates we take to be the true incidence of mental retardation in NF1, evidence shows that such developmental disability is not part of the NF1 phenotype. When it occurs in this way, a distinctive and more complex phenotype is recognisable. To claim that there is a potential simple relation between NF1 and mental retardation without further substantiation would be erroneous. Choroidal abnormalities and mental retardation in neurofibromatosis type 1Authors' reply Full-Text PDF