7219 Ocular Findings in Jansen Metaphyseal Chondrodysplasia

Abstract Disclosure: F. Obiezu: None. K. Pan: None. A. Ninan: None. K.L. Roszko: None. L.S. Weinstein: None. C.R. Ferreira: None. R.I. Gafni: None. T. Magone De Quadros Costa: None. M.T. Collins: None. S. Jha: None. Jansen Metaphyseal Chondrodysplasia (JMC) is an ultra-rare disorder, with only 30 patients estimated to have the disease globally. It is caused by heterozygous pathogenic variants in PTHR1 that result in constitutive activation of parathyroid hormone type 1 receptor (PTHR1) signaling. A detailed description of craniofacial manifestations of the disease is lacking. Here we characterize the ophthalmological manifestations in patients with JMC. Six patients (4 males, 67%) with genetically confirmed JMC underwent a detailed ophthalmological evaluation, spectral-domain optical coherence tomography (OCT), craniofacial CT and 18F-NaF PET/CT scans. Median age at the time of the visit was 27.5 [IQR: 29] years. On physical examination, all patients were noted to have widely spaced eyes; 5 of the 6 had down slanted palpebral fissures, proptosis, or ptosis. Two patients had incomplete or defective closure of the eyelids (lagophthalmos), of which one had a history of progressive right facial nerve palsy with profuse epiphora. The second patient had central visual field defects, bilateral moderate optic disc pallor and bilateral retinal nerve fiber layer (RNFL) atrophy on OCT exam with bilateral optic canal narrowing on CT. Notably, comparison of these findings with a prior scan performed 5 years earlier showed progressive decrease in RNFL bilaterally. This patient had a history of prolonged intravenous bisphosphonate therapy, initiated in infancy for hypercalcemia and continued for over a decade. A third patient had normal vision, subtle temporal pallor of the optic nerve heads on dilated fundus exam, normal average RNFL, but decreased retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4 of the 6 patients compared to age-matched reference range indicating a chronic optic nerve atrophic process. These data represent the first comprehensive report of the ophthalmologic findings in a cohort of patients with JMC. They demonstrate that patients with JMC have significant eye findings that appear to be more prevalent and pronounced with age. This suggests age-related, progressive optic neuropathy, which can be assessed by demonstrating OCT retinal GCA and RNFL loss and, may be a feature of JMC. The benefit and effect of long-term bisphosphonate therapy in patients with JMC remains unclear. Patients with JMC should undergo regular ophthalmologic examination including optic nerve OCT, visual field testing, and craniofacial imaging. Presentation: 6/1/2024