Date Published: April 1, 2018
Publisher: Elsevier Science
Author(s): Nashila Hirji, Patrick D. Bradley, Shuning Li, Ajoy Vincent, Mark E. Pennesi, Akshay S. Thomas, Elise Heon, Aparna Bhan, Omar A. Mahroo, Anthony Robson, Chris F. Inglehearn, Anthony T. Moore, Michel Michaelides.
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.”
Retrospective observational case series.
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.
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.
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.
In this retrospective multicenter observational study, clinical data including best-corrected Snellen acuity, color fundus photography, SD-OCT and FAF imaging, and electrophysiological assessments were reviewed for 7 affected patients. Four patients with disease-causing variants in CNNM4 were identified at Moorfields Eye Hospital (London, United Kingdom), 1 at Casey Eye Institute (Portland, Oregon, USA), and 2 at the Hospital for Sick Children, Toronto (Canada).
Jalili syndrome is a rare autosomal recessive condition, comprising CORD in association with AI. Ocular symptoms reflecting predominantly cone photoreceptor dysfunction usually manifest in early childhood/infancy with photophobia, nystagmus, reduced visual acuity, and color vision defects. Nyctalopia and visual field defects may develop later, reflecting rod photoreceptor involvement.2, 4 AI encompasses a range of genetically heterogeneous conditions that affect dental development. It results in abnormal structure and appearance of tooth enamel, in almost all the teeth of both primary and secondary dentition. There is discoloration, sensitivity, and brittleness of teeth, with premature tooth loss.11 As well as occurring in conjunction with CORD in Jalili syndrome, AI can also occur in isolation, or within syndromes in which a wider range of tissues and organs are affected.12