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Editor,—Tuberous sclerosis is a multisystem disorder of autosomal dominant inheritance. Associated pathological ocular findings include depigmented retinal areas and retinal hamartomas.1 Less common are the iris abnormalities such as depigmentation or atypical colobomas.2-5 We report the first described case of aniridia in a patient with tuberous sclerosis.
A 62-year-old white man with inherited tuberous sclerosis, diagnosed in his early childhood, was referred for ophthalmic assessment. The classic diagnostic triad of the disease1 was present—mental retardation, epilepsy, and adenoma sebaceum (Fig 1). Systemic involvement also included documented renal hamartomas resulting in renal failure and kidney transplantation.
His past ocular history was unremarkable, including denial of ocular trauma or episodes of ocular redness. The patient denied instillation of any local treatment. The best corrected visual acuity was 20/80 in his right eye and 20/200 in his left eye. On biomicroscopic examination, corneas were clear except superficial opacification in the periphery. Both anterior chambers were deep. The left eye had an almost complete aniridia on 360°, with only a slim, unreactive portion of the iris attached to the angle (Fig 2). The patient stated that he had always noted the absence of the left iris. Pilocarpine instillation in the left eye had no effect on the iris morphology. Gonioscopy did not show presence of anterior synechiae and the angle was normal, totally open. The pupil in the other eye was round, of normal size, but the iris presented diffuse stromal defects. Intraocular pressure, as determined with aplanation tonometry was 14 mm Hg in both eyes and no signs of glaucoma were detectable. A left focal cataract was present and the lens had a minimal nasal subluxation (Fig 2). Fundus examination of the left eye revealed a yellowish-white mass above the macula, consistent with a retinal hamartoma, but the patient refused a fluorescein angiography.
Iris abnormalities such as hypopigmented spots or atypical iris colobomas are rare in patients with tuberous sclerosis. Previous reports suggest an embryological explanation of these anomalies by faulty migration of cells derived from the neural crest.3In our patient, the origin of the almost complete absence of the iris was difficult to determine. Secondary iris atrophy was ruled out by the clinical features and as there was neither history nor clinical evidence of previous surgery, trauma, acute glaucoma episodes, heterochromia, or ocular inflammation. No posterior embryotoxon or systemic stigmata of Rieger’s syndrome were evident.
The almost complete absence of the iris associated with a focal cataract, subluxation of the lens and peripheral opacification of the cornea were consistent with the diagnosis of aniridia, which is a misnomer for iris hypoplasia. Other ocular signs described in aniridia (foveal hypoplasia, nystagmus) were not found in our case. This has already been described as manifestation of the large clinical variability of the disease.6 To our knowledge, inherited aniridia, as in our patient, has never been described in tuberous sclerosis.
Aniridia is an autosomic dominant inherited disease, but sporadic non-familial forms exist. Our patient had no contact with his family and had no descendants so we were unable to document the transmission of his iris hypoplasia.
It is difficult to establish whether the occurrence of aniridia and autosomal dominant tuberous sclerosis in this same patient is coincidental or if there is a genetic link between them. Aniridia arises from mutations in the PAX6 gene located on the chromosome 11p13, resulting in a defect in the control of neural crest cell migration into the developing eye.7 In tuberous sclerosis, linkage studies revealed mutations on chromosomes 9q34 and 16p13. Genetic studies initially suggested that mutations on chromosome 11 (also involved in aniridia) might be responsible in tuberous sclerosis, but new data do not provide evidence for such a mutation.8There are no available data that could suggest a common mutation for both aniridia and tuberous sclerosis. As our patient refused genetic testing, further observations and chromosome studies are necessary to establish if occurrence of aniridia in tuberous sclerosis is stochastic or due to a genetic linkage.