|Year : 2021 | Volume
| Issue : 3 | Page : 551-553
A rare association of phakomatosis
Dharmeswari Thangaraju1, Priya Sivakumar2
1 Department of General Ophthalmology, Aravind Eye Care, Puducherry, India
2 Department of Neuro Ophthalmology and Low Vision Services, Aravind Eye Care, Puducherry, India
|Date of Submission||14-Aug-2020|
|Date of Acceptance||25-Feb-2021|
|Date of Web Publication||02-Jul-2021|
Dr. Priya Sivakumar
Department of Neuro Ophthalmology and Low Vision Services, Aravind Eye Care, Puducherry - 605 007
Source of Support: None, Conflict of Interest: None
Simultaneous occurrence of neurofibromatosis and tuberous sclerosis is very rare. A 55-year-old hypertensive man was referred for ophthalmic evaluation. On examination, Lisch nodules were seen over the iris in both the eyes with fundus showing bilateral temporal pallor. Magnetic resonance imaging (MRI) brain was done to rule out optic pathway gliomas. MRI brain was negative for gliomas but showed subependymal nodules in the ventricles, a feature of Tuberous sclerosis. A screening computed tomography (CT) abdomen showed multiple angiomyolipoma in the kidney, which confirmed the diagnosis. It is important to be aware of this rare co-existence so that a devastating consequence can be prevented.
Keywords: Neurofibromatosis, temporal pallor, tuberous sclerosis
|How to cite this article:|
Thangaraju D, Sivakumar P. A rare association of phakomatosis. Indian J Ophthalmol Case Rep 2021;1:551-3
Neurocutaneous syndromes represent one of the most common inherited disorders of the nervous system. Neurofibromatosis type 1 (NF1) and tuberous sclerosis are well described. Yet, the presentation of both syndromes in the same patient is quite rare. A total of 14 cases of tuberous sclerosis complex (TSC) complicated by NF1 have been reported (Schull 1953; Alaraj 2007; Janeiro 2008; Suttur 2009). Two of these were sporadic TSC complicated by sporadic NF1, and only two cases have been reported as sporadic incomplete TSC complicated by mosaic localized NF1.,,, In this case report, we demonstrate this rare association of neurofibromatosis with tuberous sclerosis.
| Case Report|| |
Our case was a 55-year-old man, known hypertensive and neurofibromatosis [Figure 1], referred for ophthalmic evaluation, presented with defective vision in both eyes for the past 4 months. On examination, his best-corrected visual acuity (BCVA) right eye was 6/12 and that of the left eye was 6/18. His anterior segment examination of both eyes showed Lisch nodules over the surface of the iris and early cataract. Fundus showed temporal pallor in both the eyes [Figure 2], with no evidence of disc edema with grade 2 Hypertensive retinopathic changes. Investigations revealed defective color vision and peripherally constricted fields. On general examination, he had multiple neurofibromas, which he had since childhood. No associated lesions such as Café au lait spots, shagreen patches, and hypopigmented macules were observed.
|Figure 1: Colour photograph of the patient showing multiple neurofibromas with wide distribution over the face and the neck|
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|Figure 2: Standard color fundus photograph of right and left eye showing bilateral mild temporal pallor|
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Magnetic resonance imaging (MRI) brain was done to rule out optic pathway gliomas that are commonly associated with neurofibromatosis type 1, as, 15%–20% develop optic pathway glioma in neurofibromatosis type 1. MRI brain was negative for gliomas but showed subependymal nodules in the ventricles with bilateral frontoparietal cortical tubers [Figure 3]a, [Figure 3]b, a feature of tuberous sclerosis, with no evidence of raised ICT. A screening computed tomography (CT) abdomen, showed bilateral multiple angiomyolipoma in kidney [Figure 3]c, [Figure 3]d, which confirmed the diagnosis of tuberous sclerosis. A biopsy taken from the neurofibroma showed histopathological features suggestive of neurofibromatosis [Figure 4].
|Figure 3: (a)- Axial section of MRI brain- FLAIR, Enlarged view, showing cortical tubers (marked in white arrow) and subependymal nodules seen within the ventricular cavity (arrow marked in red). (b)- MRI brain with contrast sagittal view showing sub ependymal nodules within the third ventricle (shown by solid black arrow). (c)- CT abdomen transverse view enhancing the position of angiomyolipomas (lesions seen within the yellow circles). (d)- CT abdomen longitudinal view with bilateral kidneys showing multiple angiomyolipoma (Marked in red diamond)|
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|Figure 4: (a): HPE picture of the NF showing Circumscribed proliferation of spindle cells in dermis (4x magnification). (b): HPE picture of the NF-Tumor composed of benign spindle cells with wavy nuclei admixed with mast cells (blue arrows) (40x magnification)|
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According to the diagnostic criteria for TSC, established by the International Tuberous Sclerosis Complex Consensus Group, last updated in 2012 [Table 1], our patient fulfilled thee major criteria (cortical tubers, subependymal nodules, renal angiomyolipoma ≥2), arriving at a diagnosis of tuberous sclerosis, in association with neurofibromatosis.
|Table 1: Demonstrates the International Tuberous sclerosis Consensus group .2012; Diagnostic criteria for Tuberous sclerosis Complex|
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| Discussion|| |
Neurofibromatosis and tuberous sclerosis are phakomatosis. Both are transmitted as autosomal dominant conditions with a high rate of new mutations and similar clinical features. However, the two disorders have distinct and well-delineated genetic, biochemical, and physical findings. Simultaneous occurrence of these two conditions is rare.
TSC is a complex, a multisystem disorder with a well-described underlying genetic etiology. Retinal hamartomas are common in TSC and important in establishing the diagnosis. TSC also has many potential neuro-ophthalmic manifestations, which can have a significant impact on visual function and are sometimes a sign of serious neurological disease.
The affected individuals develop tumors at an increased frequency. Presence of hypertension in neurofibromatosis, increases the risk of development of renovascular diseases, mostly tumors with vasoactive components. Although the clinical manifestations of these disorders are distinctive, the identification of the genes responsible for these disorders has demonstrated remarkable similarities on a molecular level between the NF1 and TSC tumor suppressor gene products. The overlap between the functions of these tumor suppressor genes has yielded important insights into the molecular pathogenesis underlying each of these disorders.
The two-hit hypothesis may explain the mechanisms by which the manifestations of both syndromes occur. In this hypothesis, a mutated tumor suppressor gene is inherited and is present in every cell of the body. This is the first hit, a second mutation (hit) occurs in some somatic cells of the individual, knocking out the other copy of the gene, resulting in complete loss of the gene product and upregulated cell growth and division. This results in a predisposition to cancer in the cell.
The previously reported 14 cases and its clinical features have been tabulated below, based on the available data [Table 2].
The clinical manifestations of TSC vary widely with the most common being neurologic, dermatologic, renal, cardiac, pulmonary, and ocular.
Our patient had a segmental type of neurofibromatosis, according to Riccardi classification, wherein only neurofibromas and Lisch nodules are present along with the clinical features of Tuberous sclerosis.
The temporal pallor still remained unexplained in our patient. Visual Evoked Potential showed reduced amplitude with normal latency in both the eyes. On further literature search, an article by European Society of Radiology, quotes, myelin vacuolization to be seen in 70% of patients in Neurofibromatosis and it increases with increase in age. These lesions do not show mass effect or enhancement after the administration of gadolinium. The most common location is in the basal ganglia, particularly the globus pallidus, followed by the thalamus, brainstem, hippocampus, cerebellum and optic nerve sheaths.
The patient and his family were counseled about screening and further course of the disease and prognosis and were referred to a nephrologist for management of renal angiomyolipomas. The patient underwent trans catheter arterial embolization and partial nephrectomy.
| Conclusion|| |
Neuro-ophthalmologists should be aware of the rare co-existence of Neurofibromatosis with tuberous sclerosis so that devastating consequences can be prevented.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]