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Joubert Syndrome: Ophthalmological Findings in Correlation with Genotype and Hepatorenal Disease in 99 Patients Prospectively Evaluated at a Single Center.
- Source :
-
Ophthalmology [Ophthalmology] 2018 Dec; Vol. 125 (12), pp. 1937-1952. Date of Electronic Publication: 2018 Jul 25. - Publication Year :
- 2018
-
Abstract
- Purpose: Joubert syndrome (JS) is caused by mutations in >34 genes that encode proteins involved with primary (nonmotile) cilia and the cilium basal body. This study describes the varying ocular phenotypes in JS patients, with correlation to systemic findings and genotype.<br />Design: Patients were systematically and prospectively examined at the National Institutes of Health (NIH) Clinical Center in the setting of a dedicated natural history clinical trial.<br />Participants: Ninety-nine patients with JS examined at a single center.<br />Methods: All patients underwent genotyping for JS, followed by complete age-appropriate ophthalmic examinations at the NIH Clinical Center, including visual acuity (VA), fixation behavior, lid position, motility assessment, slit-lamp biomicroscopy, dilated fundus examination with an indirect ophthalmoscope, and retinoscopy. Color and fundus autofluorescence imaging, Optos wide-field photography (Dunfermline, Scotland, UK), and electroretinography (ERG) were performed when possible.<br />Main Outcome Measures: The VA (with longitudinal follow-up where possible), ptosis, extraocular muscle function, retinal and optic nerve status, and retinal function as measured by ERG.<br />Results: Among patients with JS with quantifiable VA (68/99), values ranged from 0 logarithm of the minimum angle of resolution (logMAR) (Snellen 20/20) to 1.5 logMAR (Snellen 20/632). Strabismus (71/98), nystagmus (66/99), oculomotor apraxia (60/77), ptosis (30/98), coloboma (28/99), retinal degeneration (20/83), and optic nerve atrophy (8/86) were identified.<br />Conclusions: We recommend regular monitoring for ophthalmological manifestations of JS beginning soon after birth or diagnosis. We demonstrate delayed visual development and note that the amblyogenic time frame may last significantly longer in JS than is typical. In general, patients with coloboma were less likely to display retinal degeneration, and those with retinal degeneration did not have coloboma. Severe retinal degeneration that is early and aggressive is seen in disease caused by specific genes, such as CEP290- and AHI1-associated JS. Retinal degeneration in INPP5E-, MKS1-, and NPHP1-associated JS was generally milder. Finally, ptosis surgery can be helpful in a subset of patients with JS; decisions as to timing and benefit/risk ratio need to be made on an individual basis according to expert consultation.<br /> (Published by Elsevier Inc.)
- Subjects :
- Abnormalities, Multiple genetics
Adolescent
Adult
Blepharoptosis diagnosis
Blepharoptosis genetics
Child
Child, Preschool
Electroretinography
Eye Abnormalities genetics
Eye Diseases genetics
Female
Hepatorenal Syndrome genetics
High-Throughput Nucleotide Sequencing
Humans
Infant
Kidney Diseases, Cystic genetics
Male
Nystagmus, Pathologic diagnosis
Nystagmus, Pathologic genetics
Ocular Motility Disorders diagnosis
Ocular Motility Disorders genetics
Ophthalmoscopy
Polymerase Chain Reaction
Prospective Studies
Retinal Degeneration diagnosis
Retinal Degeneration genetics
Retinoscopy
Slit Lamp Microscopy
Visual Acuity physiology
Exome Sequencing
Young Adult
Abnormalities, Multiple diagnosis
Cerebellum abnormalities
Eye Abnormalities diagnosis
Eye Diseases diagnosis
Genotype
Hepatorenal Syndrome diagnosis
Kidney Diseases, Cystic diagnosis
Retina abnormalities
Subjects
Details
- Language :
- English
- ISSN :
- 1549-4713
- Volume :
- 125
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Ophthalmology
- Publication Type :
- Academic Journal
- Accession number :
- 30055837
- Full Text :
- https://doi.org/10.1016/j.ophtha.2018.05.026