Table 7.3  Clinical diagnosis criteria of neurofibromatosis type 1. The criteria were formulated by the National Institute of Health Consensus Development Conference [2]

Presence of any two or more of the following clinical features

been found however, genotype-phenotype correlation is not apparent [13]. Individuals with the same gene mutation present with considerably variable phenotype. Unknown factors are believed to be critical in determining the clinical manifestations.

The NF1 locus comprises 60 exons spanning 350 kilobases. The large size of the NF1 gene makes routine diagnostic mutation screening difficult. Commercially available testing for NF1 mutation traditionally relies on protein truncation test with a yield of less than 80%. Addition of heteroduplex analysis and fluorescent in situ hybridization (FISH) to protein truncation test increases the detection rate to 95% [14]. However, the clinical application of genetic testing in NF1 is limited, because the diagnosis of NF1 can be reliably made by physical examination, and genotyping gives no information on phenotype.

7.2.1.5  Natural History and Prognosis

NF1 mainly involves the peripheral nervous system, skin, and bone with variable clinical manifestations. Presentation of specific clinical characteristics is age dependent. Although the majority of tumors in NF1 are benign, malignant transformation, particularly of the

peripheral nerve sheath, occurs in approximately 5% of the patients [15]. Mental retardation, learning difficulties, and other behavior problems are common [16].

7.2.1.6  Signs and Symptoms

Clinical presentation of NF1 can be categorized into ocular and systemic findings. The most common and significant features are Lisch nodules, optic nerve glioma, café-au-lait spots, and neurofibroma.

7.2.2  Ocular Manifestations

7.2.2.1  Lisch Nodules

Lisch nodules are the most common ocular manifestation of NF1. They are asymptomatic and are detectable with slit-lamp examination as multiple, tan-colored, dome-shaped nodules of the iris surface (Fig. 7.1). Histopathologically, these nodules are composed of pigmented cells, fibroblast-like cells, and mast cells. The presence of Lisch nodules correlates with age but not with the severity of disease [4]. The prevalence of Lisch nodules gradually increases from birth to about 50% at 5 years of age, 75% at 15 years of age, and more than 90% in adults [3]. Treatment is unnecessary because these asymptomatic nodules do not undergo malignant transformation.

Fig. 7.1  Slit-lamp photograph of the right eye showing multiple Lisch nodules. Reproduced with permission from: Singh et al. [228]