Introduction
Neurofibromatosis 1 (NF1), also known as von Recklinghausen, is a rare disease that is part of the spectrum of neurofibromatoses. Its genetic and clinical aspects differ from one entity to another. Alongside NF1, we find NF2 and Schwannoma. Its incidence is estimated at 1/3000 cases. In 50% of cases, NF1 appears de novo in patients with no family history of neurofibromatosis. We report the observations of two young female patients who presented with Lisch nodules as part of their disease.
Observations
Clinical case n°1
This 22-year-old patient had been followed since childhood for NF1. General examination revealed café-au-lait spots on her both arms and her back, aside from cutaneous neurofibromas on the face (Figure 1). She was referred to us for ophthalmological investigation in the context of her disease. Examination of the right eye revealed a corrected visual acuity of 10/10. Slit-lamp examination revealed 4 small iris elevations with slightly downy margins corresponding to Lisch nodules, measuring 1, 1.5, and 2 mm respectively, and located at 2, 3, 4, and 7 o'clock (Figure 2a). In the left eye, corrected visual acuity was also 10/10, with the same types of iridocorneal nodules located at 9 and 11 o'clock, measuring 0.5 and 1 mm respectively (Figure 2b). The iridocorneal angle was open through 360° without individualization of nodules. The photomotor reflex was preserved in both eyes, both direct and consensual. Intraocular pressure was 14mmHg and fundus examination was without abnormalities, notably no optic nerve damage.
Clinical case n°2
The 2nd patient is an 8-year-old girl whose family history included a father with NF1 who died of a central nervous system tumor (a complication of his disease). General examination revealed café-au-lait lesions on the face, neck, both arms and chest. Visual acuity was preserved in both eyes at 10/10. The anterior segment showed three Lisch's nodules on the right eye and one on the left. The direct and consensual photomotor reflex was preserved. Examination of the iridocorneal angle was normal in both eyes. Fundus examination revealed no optic nerve damage.
Discussion
Ocular manifestations of Von Recklinghausen disease are frequent and may reveal the disease. An ophthalmological examination should always be carried out if neurofibromatosis is suspected. In the anterior segment, the lesions to look for are Lisch nodules. They were described in 1937, as small pigmented hamartomas most often found in the lower iris. They can be spotted without high magnification by using a slit lamp to study the iris stroma. They are primarily seen in NF1. Their prevalence is higher in sporadic cases than in familial cases. They represent the most frequent ocular manifestation of NF1 as they are present in over 90% of adult neurofibromatosis patients where they generally appear between the ages of two and six.
The number of nodules increases with age but is not correlated with disease severity. Their prevalence increases progressively from 0% at birth to 75% in adolescence and 90% in adulthood. Lisch nodules can be particularly useful in the diagnosis of NF1 within young children with multiple café-au-lait spots and no family history of neurofibromatosis, as these lesions appear before neurofibromas. Their presence is one of the major criteria in the positive diagnosis of neurofibromatosis type 1. In the absence of other signs of NF1, their presence is highly suggestive of NF1. Therefore, there is no correlation between the presence of these nodules and the severity of the disease.
Table 1: Diagnostic criteria for neurofibromatosis
The positive diagnosis of neurofibromatosis is based on the presence of at least two of the above-mentioned criteria.
| Criteria |
|---|
| 1. Six or more café au lait macules whose largest diameter is > 5 mm in prepubertal individuals and > 15 mm in postpubertal individuals |
| 2. Two or more neurofibromas of any type or one plexiform neurofibroma |
| 3. Freckles in axillary or inguinal areas |
| 4. Optical glioma |
| 5. Two or more Lisch nodules |
| 6. A distinctive bone lesion such as sphenoid dysplasia or thinning of the cortex of the long bones, with or without pseudarthrosis |
| 7. A first-degree relative (parent, sibling, or offspring) with NF-1 according to the above criteria |
Less frequent lesions can be found in the posterior segment. Astrocytic hamartomas, typically seen in tuberous sclerosis, are also described in NF1. Capillary hemangiomas and combined retinal and pigment epithelial hamartomas may also be seen. Vision-threatening complications such as retinal detachment, neovascular glaucoma, and vitreous hemorrhage have been associated with the disease.
99% of patients with NF1 acquire café-au-lait macules before the age of one year, making them the most prevalent dermatological finding. These hyperpigmented lesions range from light to dark brown and are the result of increased melanocyte proliferation.
Optic nerve gliomas can be visually devastating. This is the most common central nervous system tumor to occur in NF1. Optic nerve astrocytoma is the most frequent type.
Neurofibromas are feared in the disease. Their number varies from one individual to another. The sex ratio is 1:1. They are at risk of malignant degeneration with metastatic risk compromising the vital prognosis, as was probably the case for the father of the 2nd patient.
Conclusion
Ocular manifestations in neurofibromatosis are easily assessed by slit lamp. Lisch nodules are one of the most frequent manifestations, unrelated to the severity of the disease. Prognosis is compromised by the presence of central nervous system gliomas or neurofibromas, with a risk of degeneration.
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