Abstract
Purpose:
To characterise the retinal phenotype in patients confirmed to have a mutation in the BBS1 gene, the commonest known gene harbouring mutations in Bardet-Biedl syndrome.
Methods:
71 patients (ages 18-55 years) with confirmed mutations in the BBS1 gene were subject to full ophthalmic examination as part of a UK national multidisciplinary clinic for adults with BBS, along with some additional ancillary testing including OCT scans.
Results:
58 patients were homozygous for M390R, the commonest known disease causing allele, 9 patients had compound heterozygosity in BBS1 including one M390R allele, whilst the remaining 4 patients had other novel mutations in BBS1. The phenotype was categorised according to changes documented at the fovea, the remainder of the macula and the peripheral retina, according to a classification scheme we developed for our clinical service. We formally defined standard degrees of change categorised as none, mild, moderate and severe at each of these locations, graded by two observers, and then analysed these changes per decade of life. We find that whilst all the teenagers in our cohort were uniformly recognised to have what we defined as only mild changes at all retinal locations, those individuals in their 50s invariably had severe degrees of atrophy at the fovea and the macula, whilst the retinal periphery showed heavy pigmentary degeneration in 82% of cases. Those patients in their 20s, 30s and 40s appeared to show a trend towards a linear progressive decline in the status of their retinopathy between the teens and 50s. However, some intra-familial variability was seen, with younger siblings appearing worse on occasion. The structural degenerative change also seemed to lag visual function; the vast majority (92%) were registered legally blind by the age of 30 with no cases maintaining acuity better than light pereption by the age of 50.
Conclusions:
This is the largest cohort of BBS1 patients reported to date and clearly demonstrates the progressive nature of the retinal degeneration. Whilst classic BBS is recognised to encompass sparse pigmentary degeneration and atrophic macular changes; this description primarily appears to hold true for younger patients only. A wider spectrum of degenerative change is seen from the 3rd decade of life onwards, by the 6th decade of life the retina consistently shows advanced end-stage degeneration.
Keywords: 649 photoreceptors: visual performance •
696 retinal degenerations: hereditary •
688 retina