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


CONCLUSIONS
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.
Labauge
Pierre
P
Department of Neurology, Centre Hospitalo-Universitaire de Montpellier-Nîmes, Montpellier, France. labauge@hotmail.com
Krivosic
Valerie
V
Denier
Christian
C
Tournier-Lasserve
Elisabeth
E
Gaudric
Alain
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D017353:Gene Deletion; D005787:Gene Frequency; D006392:Hemangioma, Cavernous / Q000453:epidemiology / Q000235:genetics*; D020786:Hemangioma, Cavernous, Central Nervous System / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D000075927:KRIT1 Protein; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D017354:Point Mutation; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019572:Retinal Neoplasms / Q000453:epidemiology / Q000235:genetics*
D051017:Apoptosis Regulatory Proteins; C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins