Frequency of retinal cavernomas in 60 patients with familial cerebral cavernomas: a clinical and genetic study.

OBJECTIVES

To define the frequency of retinal lesions in a large panel of patients with familial cerebral cavernomas and to screen the cerebral cavernous malformation genes in patients with cerebral and retinal lesions.

METHODS

Fundus examination was proposed to each of the index patients of 70 families with cerebral cavernous malformation who have been included in a prospective clinical and neuroradiological follow-up. All of the coding exons of the KRIT1, MGC4607, and PDCD10 genes were screened as previously described.

RESULTS

Of the 70 index patients, 60 were consecutively examined. The 10 remaining patients refused the fundus examination. Three of the 60 examined patients had a retinal cavernoma diagnosis. Three mutations were found: a point mutation within exon 5 of the KRIT1 gene, a large deletion that encompassed exons 1 and 2 of the MGC4607 gene, and a large genomic de novo deletion encompassing the whole PDCD10 gene.

CONCLUSIONS

Retinal cavernoma frequency can be estimated to be about 5% of the patients with familial cerebral cavernomas. Retinal cavernomas are not restricted to KRIT1 mutation carriers but can be observed in patients carrying a mutation in any of the 3 cerebral cavernous malformation genes.

CLINICAL RELEVANCE

Five percent of patients with familial cerebral cavernomas have retinal cavernomas. These lesions are clinically asymptomatic. They can be associated with any of the 3 cerebral cavernous malformation genes.