Lisch Nodules Associated with Neurofibromatosis 1

Lisch nodules are tumors that present as tiny, pigmented bumps on the iris surface. These tumors of nerve tissue are usually benign in the eye but may become malignant in other parts of the body.¹

The nodules are associated with a genetic disorder known as neurofibromatosis 1 (NF1, a.k.a. von Recklinghausen’s disease). NF1 is the most common form of neurofibromatosis, accounting for approximately 90% of cases.² It is one of the most common genetic diseases, occurring in about 1 in 3,000 births. NF1 is inherited as autosomal dominant with 80% penetrance; however, it also may result from a spontaneous mutation.³

The other two forms are known as neurofibromatosis 2 (NF2) and schwannomatosis. NF2 is far less common and usually involves the ears in the form of acoustic neuromas, although occasionally the optic nerve and other nerves of the body may be involved.¹ Rarer still is schwannomatosis, which is estimated to occur in 1 in 33,000 to 40,000 births.⁴

When iris pigmentation leads practitioners to suspect Lisch nodules, additional questions about unusual skin pigmentation—such as non-elevated brown lesions (café au lait spots) or freckles in the armpits or groin—are indicated. If a patient reports having six or more café au lait spots, this is highly indicative of NF1 and should be investigated.¹

Other ocular complications have been reported. Kim et al reported thickening of the tarsal conjunctiva of a 46-year-old woman who had a confirmed diagnosis of NF1.⁵ There was no effect on vision, so no treatment was indicated.

Accurate diagnosis is important, because systemic manifestations may be severe. Takeshima et al published a case involving eight cerebral aneurysms in a 67-year-old female diagnosed with NF1.⁶ She was treated successfully with surgery.

References

1. Mayo Clinic. Neurofibromatosis. Available at https://www.mayoclinic.org/diseases-conditions/neurofibromatosis/symptoms-causes/syc-20350490 . Accessed Dec. 30, 2019.
2. Ghalayani P, Saberi Z, Sardari F. Neurofibromatosis type 1 (von Recklinghausen’s disease): A family case report and literature review. Dent Res J (Ishfahan). 2012 Jul;9:483-488.
3. Tsang SH, Sharma T. Neurofibromatosis. Adv Exp Med Biol. 2018;1085:209-211.
4. Wolkenstein P, Decq P. [Neurofibromatosis] [Article in French]. Neurochirurgie. 1998 Nov;44:267-272.
5. Kim JY, Lee MY, Lee YC, Shin HY. Neurofibromatosis type 1 with tarsal conjunctiva thickening: A case report. Medicine (Baltimore). 2019 Aug;98:e16699.
6. Takeshima Y, Kaku Y, Nishi T, Mukasa A, Yamshiro S. Multiple Cerebral Aneurysms Associated With Neurofibromatosis Type 1. J Stroke Cerebrovasc Dis. 2019 Jul;28:e83-e91.
7. Kresak JL, Walsh M. Neurofibromatosis: A Review of NF1, NF2 and Schwannomatosis. J Pediatr Genet. 2016 Jun;5:98-104.