Ocular findings in Jansen metaphyseal chondrodysplasia

Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous PTHR1 variants resulting in constitutive activation of parathyroid hormone type 1 receptor. A description of ocular manifestations of the disease is lacking. Six patients with JMC underwent a detailed ophthalmic evaluation, spectral-domain optical coherence tomography (OCT), visual field testing, and craniofacial CT scans. Five of 6 patients had good visual acuity. All patients had widely spaced eyes; 5/6 had downslanted palpebral fissures. One patient had proptosis, and another had bilateral ptosis. Two patients had incomplete closure of the eyelids (lagophthalmos), one had a history of progressive right facial nerve palsy with profuse epiphora, while the second had advanced optic nerve atrophy with corresponding retinal nerve fiber layer (RNFL) thinning on OCT and significant bilateral optic canal narrowing on CT scan. Additionally, this patient also had central visual field defects and abnormal color vision. A third patient had normal visual acuity, subtle temporal pallor of the optic nerve head, normal average RNFL, but decreased temporal RNFL and retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4/6 patients indicating a subclinical optic nerve atrophic process. None of the patients had glaucoma or high myopia. These data represent the first comprehensive report of ophthalmic findings in JMC. Patients with JMC have significant eye findings associated with optic canal narrowing due to extensive skull base dysplastic bone overgrowth that appear to be more prevalent and pronounced with age. Progressive optic neuropathy from optic canal narrowing may be a feature of JMC, and OCT GCA can serve as a useful biomarker for progression in the setting of optic canal narrowing. We suggest that patients with JMC should undergo regular ophthalmic examination including color vision, OCT, visual field testing, orbital, and craniofacial imaging. Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by overactivity of the parathyroid hormone type 1 receptor, a receptor that is important for regulating bone development. Some patients report eye problems, but these have not been well-described. We therefore performed extensive eye examinations in 6 individuals with JMC. One had progressive right-sided facial paralysis associated with eye-tearing and dryness. A second individual had decreased central vision. Using optical coherence tomography (OCT), a method which takes detailed pictures of the retina, we found thinning of the retina's nerve layers (RNFL). Computed tomography (CT) of the skull showed narrowing of the bony canal through which the optic nerve passes. A third individual had normal vision but RNFL thinning just on the sides. Analysis of ganglion cells, the nerve cells carrying signals from the retina to the brain, showed localized deterioration of the optic nerve; skull CT also revealed optic canal narrowing. These findings suggest that JMC is associated with progressive damage to the optic nerve. Thus, patients with JMC would benefit from regular eye exams including OCT and visual field testing, in addition to routine imaging. Graphical Abstract