What Is the Reduced Risk of Carrier Status in Females of X–Linked Retinal Dystrophy Families When the Fundus and ERG Are Normal?

Abstract

 

Purpose:

 

Carrier females of X–linked retinal dystrophy (XLRD) can show a variable degree of fundus and/or electroretinographic (ERG) abnormalities, although some are completely normal. Consequently, when counselling at–risk females in clinic following a normal or equivocal fundus examination and/or ERG, a reduced risk is difficult to assign. In light of recent knowledge regarding the phenotypes associated with RP2 and RPGR, we have revisited the prevalence of a normal fundus and normal ERG in those females that are known to be heterozygous. The object of this study is to compute the age–related risks of carrier–status for at–risk females who show no detectable clinical or ERG abnormalities.

 

Methods:

 

Data on retinal examination and ISCEV standard (ERG) investigations were collected for 75 obligate and/or genetically determined carriers from 43 unrelated retinal dystrophy families in which X–linked segregation was confirmed. Clinical and ERG findings consistent with carrier status were noted. These were used to estimate the prevalence of clinical abnormalities in carriers in three age–groups, <40 years, between 40–60 years and >60 years. The probability of being a carrier given a normal fundus, normal ERG, and both a normal fundus and ERG was calculated using Bayes theorem.

 

Results:

 

The table below shows the posterior probability, for a particular age group, of being a carrier given normal clinical testing and a 50% prior risk.  

 

Conclusions:

 

These data are useful in counselling at–risk females of XLRD families in the clinic. Moreover, the same data is also useful in assigning posterior probabilities to the risk of XLRD occurring in families in which XL segregation is a possibility but not confirmed.

 

Keywords: genetics • retinal degenerations: hereditary • clinical (human) or epidemiologic studies: risk factor assessment