Jalili Syndrome: Cross-sectional and Longitudinal Features of Seven Patients With Cone-Rod Dystrophy and Amelogenesis Imperfecta

Abstract

Purpose: To characterize a series of 7 patients with cone-rod dystrophy (CORD) and amelogenesis imperfecta (AI) owing to confirmed mutations in CNNM4, first described as "Jalili Syndrome."

Design: Retrospective observational case series.

Methods: Seven patients from 6 families with Jalili Syndrome were identified at 3 tertiary referral centers. We systematically reviewed their available medical records, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence imaging (FAF), color fundus photography, and electrophysiological assessments.

Results: The mean age at presentation was 6.7 years (range 3-16 years), with 6 male and 1 female patient. CNNM4 mutations were identified in all patients. The mean Snellen best-corrected visual acuity (BCVA) at presentation was 20/246 (range 20/98 to 20/399) in the right eye and 20/252 (range 20/98 to 20/480) in the left. Nystagmus was observed in all 7 patients, and photophobia was present in 6. Funduscopic findings at presentation were variable, ranging from only mild disc pallor to retinal vascular attenuation and macular atrophy. Multimodal imaging demonstrated disease progression in all 7 patients over time. Electroretinography uniformly revealed progressive cone-rod dysfunction.

Conclusions: Jalili Syndrome is a rare CORD associated with AI. We have further characterized its ocular phenotype, including describing SD-OCT, FAF, and electrophysiological features; and report several novel disease-causing sequence variants. Moreover, this study presents novel longitudinal data demonstrating structural and functional progression over time, allowing better informed advice on prognosis.

Figure 1

Fundus autofluorescence imaging of Patient 3. (Top left) Perifoveal ring of increased autofluorescence in the right eye. (Top right) Similar findings in the left eye. Repeat imaging 5 years later demonstrated a significant increase in the size of the rings, in both the right eye (Bottom left) and left eye (Bottom right).

Figure 2

Images demonstrating the phenotype of Patient 5. Fundus appearances at presentation showing tilted optic discs, loss of the foveal light reflex, and mild vascular attenuation in the right eye (Top left) and left eye (Top right). Fundus autofluorescence imaging 3 years later showed generalized hyperautofluorescence in the posterior pole as well as a ring of hyperautofluorescence around the fovea in both the right (Middle left) and left (Middle right) eyes. (Bottom left) Teeth at presentation, demonstrating enamel hypoplasia and the presence of crowns. (Bottom right) Teeth 3 years later, after upper teeth had been resurfaced.

Figure 3

Color fundus images of Patient 7. Bilateral macular atrophy with retinal pigment migration, in the right eye (Top left) and left eye (Top right), at age 22 years. Repeat imaging 5 years later demonstrated advancement of pigmentary changes and increased macular atrophy in both the right eye (Bottom left) and left eye (Bottom right).