Novel ophthalmic findings and deep phenotyping in Williams-Beuren syndrome.

Background/aims: To characterise the ocular manifestations of Williams-Beuren syndrome (WBS) and compare these to patients with isolated elastin mediated supravalvular aortic stenosis (SVAS).

Methods: Fifty-seven patients with a diagnosis of WBS and five with SVAS underwent comprehensive ophthalmic evaluation at the National Institutes of Health from 2017 to 2020, including best-corrected visual acuity, slit-lamp biomicroscopy, optical biometry, dilated fundus examination, optical coherence tomography and colour fundus imaging.

Results: Mean age of the 57 WBS patients was 20.3 years (range 3-60 years). Best-corrected visual acuity ranged from 20/20 to 20/400 with mean spherical equivalent near plano OU. Twenty-four eyes (21.8%) had an axial length (AL) less than 20.5 mm and 38 eyes (34.5%) had an AL measuring 20.5-22.0 mm. Stellate iris and retinal arteriolar tortuosity were noted in 30 (52.6%) and 51 (89.5%) WBS patients, respectively. Novel retinal findings in WBS included small hypopigmented retinal deposits (OD 29/57, OS 27/57) and broad foveal pit contour (OD 44/55, OS 42/51). Of the five patients with SVAS, none had stellate iris or broad foveal pit contour while 2/5 had retinal arteriolar tortuosity.

Conclusion: WBS is a complex multisystem genetic disorder with diverse ophthalmic findings that differ from those seen in isolated elastin mediated SVAS. These results suggest other genes within the WBS critical region, aside from , may be involved in observed ocular phenotypes and perhaps broader ocular development. Furthermore, retinal arteriolar tortuosity may provide future insight into systemic vascular findings in WBS.