Neuronal Ceroid Lipofuscinosis: The National Eye Institute Experience with Retinal Dystrophy Panel Testing
Laryssa A. Huryn MD; Amy Turriff MS; Catherine Cukras MD, PhD; Brian P. Brooks MD, PhD
National Eye Institute
Introduction: Neuronal ceroid-lipofuscinoses (NCL) are a group of inherited, neurodegenerative disorders characterized by progressive motor and cognitive decline and early death. Vision loss due to retinal degeneration is a common feature and in some cases, the first presenting symptom.
Methods: Patients underwent evaluation at the National Eye Institute’s Ophthalmic Genetics clinic, including medical and ocular history, visual acuity measurements, dilated fundoscopic examination and when possible, electroretinography, optical coherence tomography and fundus imaging. Patients with clinical diagnosis of retinal degeneration were offered genetic testing with a multi-gene retinal dystrophy panel.
Results: Four patients were found to have genetic testing results associated with NCL (three with mutations in CLN3 and one in CLN1). At the time of their initial evaluation, none of the patients had a diagnosis of seizure disorder or any reported neuro-cognitive deficits. With time, all four have demonstrated personality and behavioral changes, some level of cognitive decline, with one patient developing seizures and cortical atrophy on MRI.
Discussion: Neurodegenerative disease should be considered in all pediatric patients who present for evaluation of retinal degeneration since visual complaints may be the first manifestation of the condition. Additionally, common diagnoses such as Attention Deficit Hyperactivity Disorder may represent an initial presenting sign of neurologic decline. As genetic testing becomes more routine in ophthalmic practice, we will continue to expand the spectrum of phenotype of inherited retinal conditions.
Conclusion: Families of children with retinal degeneration who are undergoing genetic testing should be counseled on the possibility of identifying neurodegenerative disease.
References: Bozorg S, Ramirez-Montealegre D, Chung M, Pearce DA. Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) and the Eye. Survey of ophthalmology. 2009;54(4):463-471. doi:10.1016/j.survophthal.2009.04.007