CLINICAL AND HISTOPATHOLOGICAL FINDINGS IN JALILI SYNDROME.

Purpose: To correlate histopathological findings in an eye with Jalili syndrome with clinical and imaging results available before enucleation.

Design: Case report with histopathological analysis.

Subjects: Histopathological analysis of an enucleated eye from a 63-year-old woman diagnosed with Jalili syndrome.

Methods: Age at diagnosis, symptoms, personal and family history, as well as genetic testing results and previous retinal imaging were retrieved from the patient file. The ocular specimen was dissected, retinal sections prepared, and analysis with Hematoxylin Eosin staining and Fluorescent Immunohistochemistry was performed. The histopathological findings were compared with the patient's imaging results available before enucleation.

Results: The ocular specimen analyzed belonged to a 63-year-old woman with Jalili Syndrome, homozygous for the likely pathogenic c.971T>C p.(Leu324Pro) variant in the CNNM4 gene (NM_020184.3). This patient had no light perception bilaterally and suffered from bilateral painful, severe dry eye, refractory to conservative treatment for seven years before enucleation. At one month follow-up after enucleation and orbital implant placement, the socket was fully recovered, and a custom ocular prosthesis was adapted. The patient experienced total pain relief, improved quality of life, and a good cosmetic result. The histopathological analyses revealed loss of photoreceptor cells, accumulation of autofluorescent material in the subretinal space, partial preservation of the inner retinal lamination, Müller glial cell disorganization and increased number of microglial cells in the nuclear layers.

Conclusion: Our findings highlight the severe nature of this inherited retinal degenerative disease with significant damage to the outer retinal layers, absence of synaptic terminals, and loss of photoreceptors, indicating an advanced disease stage. The presence of microglial cells in the remaining nuclear layers suggests a role in photoreceptor degeneration. This study represents the first comprehensive description of clinical, genetic, imaging, and histopathological findings in Jalili Syndrome.