Abstract
Purpose :
AHI1, Abelson helper integration site 1 encodes Jouberin, is mutated in Joubert Syndrome, and is required for both cortical and cerebellar development in humans.We here study a Joubert Syndrome patient with a severe retinal dystrophy, an AHI1 deletion, a non-vascularized peripheral retina and discuss a literature review.
Methods :
Complete ophthalmic evaluation, imaging by fluorescein angiography, genotyping by retinal gene-array panel and a literature review in Pubmed were performed.
Results :
A 5-year-old Cree, Canadian girl was diagnosed with Joubert syndrome and presented with a bilateral severe retinal dystrophy and unique characteristics on fluorescein angiography imaging. She was born to consanguineous parents at 36 4/7 weeks of gestation, following an urgent C-section for pre-eclampsia. Her birth weight was 2680 grams. At the age of 7 weeks, while being hospitalized for fever and lethargy, she was noted to have poor fixation, oculomotor apraxia and gaze evoked nystagmus. Brain MRI showed cerebellar hypoplasia, along with the classic “molar tooth sign” in keeping with Joubert syndrome. Her clinical findings included retinal degeneration, strabismus, ataxia, axial hypotonia and hyperreflexia. A genetic work up revealed that she was homozygous for an AHI1 splice-site mutation. In particular, a deletion of 4 base-pairs was found, predicted to cause a frameshift and a premature stop. At the age of 5 years, a dilated fundus examination revealed peripheral RPE mottling and vessel abnormalities. Most importantly, the retinal vasculature was grossly abnormal: there were no vessels past anterior zone 2 in the right eye, and no vessels past mid zone 2 in the left eye. The optic nerves were unremarkable. Fluorescein angiography subsequently confirmed bilateral non-perfusion of the peripheral retina (attached Fig. 1 a and b).
Conclusions :
Joubert syndrome is a rare ciliopathy that can be associated with coloboma, optic nerve atrophy and retinal degeneration and can be caused by mutations in AHI1. Retinal findings are often early onset and severe with pigmentary changes, atrophy and photoreceptor loss, similar to that of Leber Congenital Amaurosis. To our knowledge, after a literature review, this appears to be the first case describing immature retinal vascularization and peripheral retinal non-perfusion. AHI1 thus plays a role in retinal vascular development.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.