Yasunari Nodules: A New Sensitive and Specific Marker of Neurofibromatosis Type 1, Readily Detectable by Ophthalmologists

Introduction

Neurofibromatosis type I (NF1) is an autosomal dominant disease caused by a defect in a single gene (NF1) on chromosome 17q11.2 [1]. However, the rate of new mutations is about 1/10 000 births, accounting for nearly half of NF1 cases [2]. Amongst the general population, the incidence of NF1 is around 1/3000 people [3]. The diagnosis of NF1 rests upon clinical findings and specific diagnostic criteria have been defined ([Table 1]). The presence of at least two criteria is needed to diagnose NF-1 [4]. Genetic testing is reserved for procreation decisions, when NF1 is suspected but not clinically confirmed [5]. The ophthalmic manifestations of NF1 include Lisch nodules, choroidal hamartomas, neurofibromas on eyelids, presumed conjunctival neurofibroma, prominent corneal nerves, glial tissue overlying optic disc, and optic pathway glioma [6]. Only Lisch nodules and optic pathway glioma are ophthalmic clinical criteria accounting for the diagnosis of NF1.

• References

• 1 Trovo-Marqui AB, Tajara EH. Neurofibromin: a general outlook. Clin Genet 2006; 70: 1-13
• 2 Lázaro C, Ravella A, Gaona A. et al. Neurofibromatosis type 1 due to germ-line mosaicism in a clinically normal father. N Engl J Med 1994; 331: 1403-1407
• 3 Lammert M, Friedman JM, Kluwe L. et al. Prevalence of neurofibromatosis 1 in German children at elementary school enrollment. Arch Dermatol 2005; 141: 71-74
• 4 Anonymous National Institutes of Health Consensus Development Conference Statement: Neurofibromatosis. Arch Neurol 1988; 45: 575-578
• 5 Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13: 834-843
• 6 Huson S, Jones D, Beck L. Ophthalmic manifestations of neurofibromatosis. Br J Ophthalmol 1987; 71: 235-238
• 7 Yasunari T, Shiraki K, Hattori H. et al. Frequency of choroidal abnormalities in neurofibromatosis type 1. Lancet 2000; 356: 988-992
• 8 Kurosawa A, Kurosawa H. Ovoid bodies in choroidal neurofibromatosis. Arch Ophthalmol 1982; 100: 1939-1941
• 9 Byun YS, Park YH. Indocyanine green angiographic findings of obscure choroidal abnormalities in neurofibromatosis. Korean J Ophthalmol 2012; 26: 230-234
• 10 Nakakura S. Quantification and anatomic distribution of choroidal abnormalities in patients with type I neurofibromatosis. Graefes Arch Clin Exp Ophthalmol 2005; 243: 980-984
• 11 Moramarco A, Giustini S, Nofroni I. et al. Near-infrared imaging: an in vivo, non-invasive diagnostic tool in neurofibromatosis type 1. Graefes Arch Clin Exp Ophthalmol 2017; 256: 307-311