Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium.
Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium.
Genes (Basel). 2019 Jul 12;10(7):528. doi: 10.3390/genes10070528.
Occipital horn syndrome (OHS) is a rare connective tissue disorder caused by pathogenic variants in ATP7A, encoding a copper transporter. The main clinical features, including cutis laxa, bony exostoses, and bladder diverticula are attributed to a decreased activity of lysyl oxidase (LOX), a cupro-enzyme involved in collagen crosslinking. The absence of large case series and natural history studies precludes efficient diagnosis and management of OHS patients. This study describes the clinical and molecular characteristics of two new patients and 32 patients previously reported in the literature. We report on the need for long-term specialized care and follow-up, in which MR angiography, echocardiography and spirometry should be incorporated into standard follow-up guidelines for OHS patients, next to neurodevelopmental, orthopedic and urological follow-up. Furthermore, we report on ultrastructural abnormalities including increased collagen diameter, mild elastic fiber abnormalities and multiple autophagolysosomes reflecting the role of lysyl oxidase and defective ATP7A trafficking as pathomechanisms of OHS.
枕角综合征（OHS）是一种罕见的结缔组织疾病，由编码铜转运蛋白的 ATP7A 种系变异引起。主要的临床特征，包括皮肤松弛、骨外生骨和膀胱憩室，归因于赖氨酰氧化酶（LOX）活性降低，LOX 是一种参与胶原交联的铜酶。缺乏大型病例系列和自然病史研究妨碍了 OHS 患者的有效诊断和管理。本研究描述了两名新患者和文献中先前报道的 32 名患者的临床和分子特征。我们报告了对长期专门护理和随访的需求，其中磁共振血管造影、超声心动图和肺量测定应纳入 OHS 患者的标准随访指南，除了神经发育、骨科和泌尿科随访。此外，我们还报告了超微结构异常，包括胶原直径增加、轻微的弹性纤维异常和多个自噬溶酶体，反映了赖氨酰氧化酶的作用和 ATP7A 转运缺陷作为 OHS 的病理机制。
