Congenital hypertrophy of the retinal pigment epithelium as a marker for familial adenomatous polyposis

Abstract

Fifty patients were assessed for congenital hypertrophy of the retinal pigment epithelium (CHRPE) as a potential phenotypic marker for familial adenomatous polyposis (FAP), with and without other extracolonic manifestations (ECM). The ocular anomaly, which characteristically is multiple, benign, and congenital, was studied in three groups. Group 1 contained eight patients with nonpolyposis colon cancer as disease controls. All had negative eye findings. Group 2 included 40 patients with FAP, 35 (87.5 percent) of whom had retinal lesions. Twenty-two of 25 patients with FAP alone had retinal lesions while 13 of 15 patients with FAP and extracolonic manifestations were similarly affected. Group 3 included 11 offspring at risk for FAP. Eight (72.7 percent) offspring had retinal lesions. One of the eight subjects with the ocular trait was subsequently diagnosed with FAP. Two of the eight patients also had other ECM but have not been sigmoidoscoped for FAP. Seven of 11 offspring (mean age, 12.5 years) have had negative flexible sigmoidoscopy. Specificity of the retinal lesions in FAP cannot be ascertained until subsequent adenomas are identified on follow-up of the group at risk. The gene responsible for CHRPE appears to be transmitted from one generation to another, demonstrated by the high sensitivity of the retinal lesions in patients with FAP alone and with other ECM.

Mutation spectrum of the APC gene in 83 Korean FAP families

“…Congenital hypertrophy of the retinal pigment epithelium lesions was classically classified into four groups according to Berk's classification (Berk et al, 1988), which most authors refer to in studies of CHRPE. We also used Berk's classification in diagnosis of CHRPE in our patients, and patients with FAP was diagnosed as CHRPE if retinal lesion was one of four type as follows: oval, pigmented, and surrounded by halo (type A); round, small, and pigmented (type B); round, large, and pigmented (type C); round, large, and depigmented (type D).…”

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer

“…Causative germline mutations in the DNA mismatch repair (MMR) genes hMSH2, hMLHI, hPMSJ and hPMS2 (Liu et al, 1996) have been identified in HNPCC families. Such mutations result in defective MMR (Parsons et al, 1993;Umar et al, 1994), manifest as instability of repetitive DNA in tumours (Ionov et al, 1993;Aaltonen et al, 1993;Thibodeau et al, 1993;Lothe et al, 1993;Aaltonen et al, 1994;Bhattacharyya et al, 1994;Liu et al, 1995a) (Traboulsi et al, 1987; Chapman et al, 1988;Berk et al, 1988; Giardello et al, 1991; Hodgson et al, 1994;Wallis et al, 1994). Because of the variety of CHRPE lesions, we devised a scoring system derived from the relative importance ascribed to each feature in previous FAP studies.…”

“…These features, congenital hypertrophy of the retinal pigment epithelium (CHRPE) and mandibular osteomas, occur in 90% and 75% respectively of patients with classical FAP (Utsunomiya and Nakamura, 1975;Bulow et al, 1984;Traboulsi et al, 1987;Berk et al, 1988;Chapman et al, 1989;Giardiello et al, 1991;Hodgson et al, 1994;Wallis et al, 1994). The finding of such extracolonic features in patients with non-FAP colorectal cancer is of considerable interest because of the central, and probably initiating, role of the gene for FAP (APC) in colorectal tumorigenesis.…”

“…Thirty patients (with and without CHRPE) were assessed by both ophthalomologists, and this ensured inter-observer reproducibility. The diagnostic criteria we used for retinal pigmentation in non-polyposis colorectal cancer patients were the same as those taken as diagnostic of CHRPE in familial adenomatous polyposis, namely: > 1 pigmented lesions with depigmented halo; >1 pigmented lesions over one optic disc diameter; > 3 small bilateral pigmented lesions without a halo or >4 small unilateral lesions (Traboulsi et al, 1987;Chapman et al, 1988;Berk et al, 1988;Giardello et al, 1991;Hodgson et al, 1994;Wallis et al, 1994). Because of the variety of CHRPE lesions, we devised a scoring system derived from the relative importance ascribed to each feature in previous FAP studies.…”

Pigmented lesions of the retinal pigment epithelium and familial adenomatous polyposis

“…More recently it has become apparent that CHRP E occurs in patients with familial adenomatous polyposis without the other extracolonic manifestations described in Gardner's syndrome. [7][8][9][10][11][12] The term Gard ner's, syndrome has tended to be replaced by familial adenomatous polyposis.…”