Are Lisch Nodules an Ocular Marker of the Neurofibromatosis Gene in Otherwise Unaffected Family Members

Abstract

A male patient with classical neurofibromatosis is reported. Examination of the other family members revealed 2 patients with solitary cutaneous neurofibromas and 2 with one or more Lisch nodules without other cutaneous or systemic signs of neurofibromatosis. This suggests that Lisch nodules can be a marker for the neurofibromatosis gene in otherwise unaffected family members.

Pigment cell‐related manifestations in neurofibromatosis type 1: an overview

“…A clear positive correlation can be seen between the number of Lisch nodules, the severity of other cutaneous manifestations and the age of the patient (Korakawa & Makita, 1977; Lewis & Riccardi, 1981; Ragge, 1993; Zehavi et al., 1986). Based on these observations the presence of Lisch nodules are virtually pathognomonic for NF1 and, therefore, they can be a very helpful diagnostic marker for NF1, especially when one tries to diagnose NF1 in children or when problematic diagnostic cases are presented (Huson et al., 1987; Toonstra et al., 1987; Zehavi et al., 1986). Attention must be drawn to the fact that, if children with multiple CALMs are found to have Lisch nodules, they are diagnosed with NF1.…”

Unilateral Lisch Nodules in a 47-year-old Woman Without Other Stigmata of Neurofibromatosis Type I: An Example of Segmental Neurofibromatosis?

“…5,8 There are also three families with parents having unilateral or bilateral LN and sons with full blown NF1 (Tenconi R personal communication). 2,9,10 The hypothesized genetic mechanisms existing in these families is a somatic ocular (eg, of the iris) and germinal mosaicism of the mutated NF1 gene in the parents, that results in a very limited ''segmental'' manifestation of NF1 (eg, LN) in the parents and in the full blown phenotype in the offspring. In contrast to the previously reported cases, our patient was older (eg, 47-years-old versus 14-and 19-year-olds), and the absence of other NF1 manifestations at this age indicates that a mosaicism for NF1 gene is limited to a very restricted area, that is the left iris, and not involving other tissues.…”

Clinical and genetic patterns of neurofibromatosis 1 and 2.

“…For instance, in the case of NFl, some parents manifesting Lisch nodules alone may give rise to offspring with a fully expressed disorder. 4 The explanation for this variable expressivity is still unclear.…”