A novel mutation in CNNM4 is associated with a case of Jalili syndrome in Egypt

To report a novel homozygous mutation in CNNM4 gene associated with Jalili syndrome (JS) which is a rare, recessively inherited oculo-dental syndrome which encompasses cone-rod dystrophy (CORD) and amelogenesis imperfecta (AI).

A 4-year-old male patient of consanguineous Egyptian parents, who presented with progressive visual impairment and tooth decay underwent complete ophthalmological examination, dental, and systemic examination. Additionally, color fundus photography, fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) of the macula, full field electroretinogram (ffERG) were obtained. Orthopantomogram (OPG) were also obtained. NGS-based gene panel testing was done in a commercial laboratory from a peripheral blood sample.

Fundus examination demonstrated typical features of CORD in the form of loss of foveal reflexes with macular retinal pigment epithelial mottling and atrophy reminiscent of bull's eye maculopathy. Dental assessment revealed evidence of AI. NGS-based gene panel identified a novel mutation in CNMM4 gene c.1423 G>A consistent with a diagnosis JS, thereby confirming the rare diagnosis.

To the best of our knowledge, this is the first report of Jalili syndrome in Egypt. We are reporting a novel mutation in CNMM4 gene. We are also expanding the clinical spectrum of dental manifestation by reporting early eruption of the first permanent molars and suggesting that hyperopia could be a rather constant feature of JS. This case emphasizes the importance of comprehensive multidisciplinary assessment beyond visual complaints in IRD patients in order to reach an accurate diagnosis.