Obiezu Fiona, Magone De Quadros Costa M Teresa, Huryn Laryssa A, Pan Kristen, Almpani Konstantinia, Ninan Anisha, Roszko Kelly L, Weinstein Lee S, Gafni Rachel I, Ferreira Carlos R, Lee Janice, Collins Michael T, Jha Smita
Skeletal Disorders & Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, United States.
National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States.
JBMR Plus. 2024 Jul 12;8(9):ziae089. doi: 10.1093/jbmrpl/ziae089. eCollection 2024 Sep.
Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous 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.
詹森干骺端软骨发育不良（JMC）是一种极其罕见的疾病，由种系杂合变异引起，导致甲状旁腺激素1型受体的组成性激活。目前缺乏对该疾病眼部表现的描述。6例JMC患者接受了详细的眼科评估、光谱域光学相干断层扫描（OCT）、视野测试和颅面部CT扫描。6例患者中有5例视力良好。所有患者均有眼距增宽；6例中有5例睑裂向下倾斜。1例患者有眼球突出，另1例有双侧上睑下垂。2例患者眼睑闭合不全（兔眼），1例有进行性右侧面神经麻痹伴大量溢泪病史，另1例有晚期视神经萎缩，OCT显示相应的视网膜神经纤维层（RNFL）变薄，CT扫描显示双侧视神经管明显狭窄。此外，该患者还存在中心视野缺损和色觉异常。第3例患者视力正常，视神经乳头颞侧轻度苍白，平均RNFL正常，但OCT显示颞侧RNFL和视网膜神经节细胞层分析（GCA）降低。6例患者中有4例GCA降低，表明存在亚临床视神经萎缩过程。所有患者均无青光眼或高度近视。这些数据代表了JMC眼科检查结果的首份综合报告。JMC患者存在与视神经管狭窄相关的明显眼部表现，这是由于广泛的颅底发育异常性骨过度生长所致，且似乎随年龄增长更为普遍和明显。视神经管狭窄导致的进行性视神经病变可能是JMC的一个特征，OCT GCA可作为视神经管狭窄情况下病情进展的有用生物标志物。我们建议JMC患者应定期进行眼科检查，包括色觉、OCT、视野测试、眼眶和颅面部成像。
