Ophthalmic and genetic screening in pedigrees with familial adenomatous polyposis

To study the possible association between ophthalmic findings, genetic status, and clinical course of the disease in Austrian pedigrees with familial adenomatous polyposis (FAP).

Thirty-nine members of 16 consecutive FAP families with 20 affected patients and 19 relatives with a 50% a priori risk to develop the disease were examined ophthalmologically. The intestinal status of all persons was established by colonoscopy. Direct or indirect molecular genetic analysis, or both, was possible in eight of the 16 FAP families.

Congenital hypertrophy of the retinal pigment epithelium (CHRPE) was discovered in 15 (75%) of the 20 persons affected by familial adenomatous polyposis. Five (25%) of the patients with an established FAP were CHRPE-negative. Four of the 19 at-risk individuals were CHRPE-positive. According to DNA analysis, five of the 19 at-risk relatives had a high risk to develop a manifest disease. The ophthalmoscopic tests were in complete agreement with the molecular risk estimation. Furthermore, the combined results of endoscopy and ophthalmoscopy suggested a relationship between a positive CHRPE status and the severity of FAP.

Ophthalmic examinations facilitate predictive diagnosis in FAP patients and first-degree relatives, permitting a noninvasive, highly reliable risk assessment. When present, CHRPE lesions are a reliable clinical marker for FAP in CHRPE-positive families. In CHRPE negative families, negative ophthalmic examinations are of no predictive value. The CHRPE status can add information about the location of the genetic mutation. The combination of an ophthalmic examination with DNA analysis and endoscopy improves the risk assessment of FAP carriers.