# Use of congenital hypertrophy of the retinal pigment epithelium as a clinical sign of familial adenomatous polyposis

## TL;DR

This study shows that a specific eye condition can help identify people at risk for a genetic disease called familial adenomatous polyposis.

## Contribution

The study identifies a new genetic mutation linked to an aggressive form of the disease.

## Key findings

- Congenital hypertrophy of the retinal pigment epithelium was found in 28.9% of evaluated individuals.
- A novel pathogenic variant c.4031del (Ser1344*) was identified in exon 16 of the APC gene.
- The eye condition is proposed as an effective first-line screening method for at-risk family members.

## Abstract

To evaluate the presence of congenital hypertrophy of the retinal pigment
epithelium in a large family affected by familial adenomatous polyposis and
identify the causative mutation in the adenomatous polyposis coli gene.
Thus, we aimed to determine the significance of congenital hypertrophy of
the retinal pigment epithelium as a phenotypic marker of the disease.

A family consisting of 95 individuals was evaluated. Among these, 45
individuals were randomly selected by convenience sampling method to undergo
ophthalmological evaluation. A funduscopic exam, including slit lamp and
indirect ophthalmoscopy, were performed in the selected patients. In those
with retinal lesions, a retinography was obtained. The adenomatous polyposis
coli gene was sequenced in one affected family member to identify the
pathogenic mutation. Once the variant was identified, six undiagnosed family
members were tested for the mutation via capillary electrophoresis
sequencing.

Congenital hypertrophy of the retinal pigment epithelium was observed in 13
(28.9%) of the 45 individuals evaluated. Of these, nine patients were
confirmed to have familial adenomatous polyposis (via colonoscopy or
molecular testing). However, four patients had not been investigated. Of the
32 (71.1%) family members without the lesion, 14 did not have familial
adenomatous polyposis and 18 were yet to be evaluated. The lesions were
bilaterally present and exhibited a peculiar fish-tail shape in all the
evaluated individuals. Adenomatous polyposis coli gene sequencing revealed a
pathogenic variant c.4031del. (Ser1344*), in heterozygosity (49.27%), in
exon 16.

The study findings confirmed the significance of congenital hypertrophy of
the retinal pigment epithelium as a phenotypic marker for familial
adenomatous polyposis. Furthermore, it is an effective first-line screening
method for at risk family members of such patients. The novel mutation
identified in our study participants, which is yet to be described in the
literature, causes an aggressive form of the disease.