Diagnosis, Workup and Treatment

The presence of symmetric and otherwise normal, fixed dilated pupils in a child with an otherwise normal eye examination is most consistent with a diagnosis of congenital hypoplasia of the iris sphincter/dilator. Given the boy’s high hyperopia and the possibility of impaired accommodation in this disorder, glasses were prescribed. Furthermore, we recommended echocardiogram to rule out structural abnormalities that have been associated with this diagnosis.


Recognizing aniridia in infants is important given the high risk for cataracts (73 percent), glaucoma (46 percent) and keratopathy (45 percent) in addition to the possible association with WAGR syndrome, and thus potentially life-threatening Wilms tumor.2 Aniridia may occur sporadically or with a positive familial history. The estimated overall prevalence is between 1:64,000 and 1:96,000.3 It is a panocular disorder characterized by variable expression which usually includes nystagmus and macular hypoplasia. Other features such as corneal pannus; cataract (in particular anterior pyramidal); glaucoma; refractive error; strabismus; and rarely, retinal degeneration may be present in patients. The iris may show a wide variety of appearances, ranging from almost complete absence to varying degrees of residual iris, usually asymmetric in a given eye and between eyes. The pupils may or may not be responsive to mydriatics, largely depending on the amount of residual iris. Persistent pupillary membrane strands may be seen, but usually only if the collarette is preserved. Aniridia may occur due to mutations or small deletions within the PAX6 gene, or as part of a larger deletion involving chromosome 11p13 that may include the WT1 gene, resulting in WAGR syndrome. Until WAGR system has been ruled out by molecular testing, renal ultrasound screening is indicated. Infants with WAGR syndrome require ongoing screening until at least 7 to 8 years old.

Recognition of congenital hypoplasia of the pupillary sphincter/dilator allows for appropriate intervention and allows elimination of concerns for ocular and renal prognosis associated with aniridia. 
The differential diagnosis of fixed dilated pupils includes other disorders. Gillespie syndrome is an extremely rare autosomal recessive syndrome that is associated with symmetric, fixed, dilated pupils with scalloped pupillary margins, persistent pupillary membrane strands, cerebellar ataxia and developmental delay.4 Instillation of mydriatic compounds, perhaps inadvertently through contact with plants (e.g., members of the genus brugmansia, such as the angel’s trumpet5,6 or ingestion of atropa belladonna berries, which can be mistaken for blueberries7) or non-ocular compounds (e.g., inadvertent contamination of the eye after handling scopolamine patches8-10 or antiperspirant powders containing diphemanil methylsulfate11), will result in fixed dilated but otherwise normal morphology pupils. Traumatic mydriasis is usually unilateral and asymmetric with an irregular pupil due to visible iris sphincter tears. Systemic disorders with bilateral mydriasis present with signs and symptoms that are usually readily apparent, for example, congenital hypoventilation syndrome (Ondine’s curse).

Congenital absence of the pupil sphincter and dilator muscle (sometimes called congenital mydriasis) is exceedingly rare, affecting far more females than males.12-17 Fewer than 20 cases have been reported in the English literature. The appearance is distinctly different from aniridia in that the iris is symmetrically enlarged beyond 6 mm and symmetric between the two eyes with an otherwise normal morphology and normal pupil margin, although the collarette may appear somewhat underdeveloped. Most importantly, the remainder of the eye examination is normal. Accommodation may be impaired.18 Rare systemic associations include patent ductus arteriosus (PDA)14,15 and thus echocardiography may be indicated. Congenital mydriasis may also occur as part of the multisystem smooth muscle dysfunction syndrome (MIM 613834) caused by mutations in the ACTA2 gene. These patients have PDA, thoracic aneurysms and other vasculopathy, and may have other evidence of smooth muscle dysfunction including hypoperistalsis. The iris malformation is often associated with iris flocculi (large cysts at the pupil margin).

In conclusion, recognition of congenital hypoplasia of the pupillary sphincter/dilator allows for appropriate intervention and allows elimination of concerns for ocular and renal prognosis associated with aniridia. Echocardiography may be utilized to rule out cardiac malformations.  REVIEW

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