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Clémence Bonnet, Dominique Monnet, Antoine P Brezin; Familial Cases of birdshot Chorioretinopathy: genetic and epidemiology. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4148. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Birdshot Chorioretinopathy (BSCR) is a rare bilateral posterior uveitis characterized by multiple hypopigmentedchoroidal lesions of unknown origin with a poor long-term visual prognosis. The disease is strongly associated with HLA-A29, found in more than 95% of individuals with BSCR. The relative risk for developing disease in HLA-A29–positive individuals has been estimated to be as high as 224. Watching familial cases of BSCR suggest the existence of a familial aggregation.Our study seeks to determine whether having relatives with birdshot disease increases one's risk of that disease. We studied the familial aggregation of BSCR by estimating the recurrence risk ratio of siblings of probands, with considering or not their HistocompatibilityLeucocyt Antigen (HLA)-A29 status.
In a cohort of 280 patients suffering of BSCR, we noted the familial cases (multiplex cases), define by at least two relatives affected by the BSCR in the same family. For each patient, clinical characteristics and HLA-A29 determination were collected. For each proband in simplex families (in wich one person is affected), the number of siblings was collected. The recurrence risk ratio lambda (ls), which gives an estimate of the weight of genetic factors, was calculated as the ratio of the recurrence risk of BSCR in first-degree relatives compared with the population prevalence of BSCR. The lambda (lnon-HLA-A29) was obtained by similar calculations restricted to HLA-A29+ individuals.
In 280 patients, we collected ninemultiplex families, representing 19 siblings patients, and 6.8 % from birdshot patients. All patients are HLA-A2902+. The prevalence of birdshot among the first degree relatives was5.5%.The overall recurrence risk was estimated to 1.54% in first-degree relatives and to 2.9% in HLA-A29+ relatives. The lambda (ls) value was estimated to1283 IC95% (901-2264) and the lambda (lnon-HLA-A29) value was 150 IC95%(106-264).
This is the first epidemiologic and genetic study of BSCR demonstrating a familial aggregation. The weight of the outside HLA-A29 genetic component is high, suggesting multiplicative interaction between HLA and non-HLA genetic components.Others genetic or environnemental factors in addition to HLA-A29 maybe critical for the development of the disease.This initial step is useful as it narrows the focus for future genetic research.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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