Shunyakova Jenny, Reynolds Margaret, Taylor Amal, Sieck Erin G, Walsh James T, Hassman Lynn M
Rocky Mountain Lions Eye Institute, University of Colorado School of Medicine, Aurora, CO, United States.
John F. Hardesty Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, United States.
Front Ophthalmol (Lausanne). 2025 Mar 25;5:1535805. doi: 10.3389/fopht.2025.1535805. eCollection 2025.
Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome is an autosomal dominant disorder caused by a heterozygous missense mutation in alpha kinase 1 (ALPK1). This series reports the presentation and treatment outcomes of three first-degree relatives with ROSAH syndrome.
Retrospective chart review, whole exome sequencing.
A 16-year-old male presented with bilateral optic disc edema, macular edema, retinal degeneration, and vitreous inflammation. His mother and brother had similar clinical features. Whole exome gene sequencing identified a shared heterozygous mutation in the ALPK1 gene c.710C>T, consistent with ROSAH syndrome. Ophthalmic manifestations in this family included optic nerve edema, macular edema, panuveitis, glaucoma, and widespread retinal cone and rod dysfunction. While the proband's macular edema improved with intravitreal dexamethasone and systemic tocilizumab, immune suppression did not prevent retinal degeneration.
A diagnosis of ROSAH syndrome, suggested by the concomitant presentation of optic disc edema, uveitis, and retinal degeneration, can be made by targeted genetic sequencing of the ALKP1 gene. While ROSAH-associated ocular inflammation and macular edema may respond to local steroids and immune suppression, retinal degeneration may progress despite these therapies.
视网膜营养不良、视神经水肿、脾肿大、无汗和头痛（ROSAH）综合征是一种常染色体显性疾病，由α激酶1（ALPK1）杂合错义突变引起。本系列报告了三名患有ROSAH综合征的一级亲属的临床表现和治疗结果。
回顾性病历审查、全外显子组测序。
一名16岁男性出现双侧视盘水肿、黄斑水肿、视网膜变性和玻璃体炎症。他的母亲和兄弟有相似的临床特征。全外显子组基因测序在ALPK1基因c.710C>T中发现了一个共同的杂合突变，与ROSAH综合征一致。该家族的眼部表现包括视神经水肿、黄斑水肿、全葡萄膜炎、青光眼以及广泛的视网膜视锥和视杆功能障碍。虽然先证者的黄斑水肿通过玻璃体内注射地塞米松和全身使用托珠单抗得到改善，但免疫抑制并不能阻止视网膜变性。
通过对ALKP1基因进行靶向基因测序，可以诊断由视盘水肿、葡萄膜炎和视网膜变性同时出现所提示的ROSAH综合征。虽然与ROSAH相关的眼部炎症和黄斑水肿可能对局部类固醇和免疫抑制有反应，但尽管进行了这些治疗，视网膜变性仍可能进展。
