儿童连接性皮肤病的临床与遗传图谱：一项范围综述。

文献信息

中文摘要

细胞连接，包括桥粒、半桥粒、黏附连接、紧密连接和缝隙连接，对于表皮完整性、屏障功能和细胞信号传导至关重要。编码参与细胞连接的蛋白质的基因变异可导致一系列皮肤病，通常称为连接性遗传性皮肤病，在儿科患者中常表现为表型重叠和多系统受累。本系统范围综述旨在全面绘制儿童遗传性皮肤病图谱，将特定遗传变异与临床表现相关联，以提高诊断和预后准确性。在PubMed、Web of Science、Embase和Scopus中进行了系统性文献综述。关键术语包括遗传性皮肤病和细胞连接；纳入针对儿科皮肤病患者的病例报告、病例系列或观察性研究，需明确连接基因并有详细临床描述。从9,409条记录中，纳入159项研究，涵盖五个连接复合体中的25个关键基因。锚定复合体的缺陷主要表现为皮肤脆性和水疱，包括致死性新生儿型遗传性皮肤病。紧密连接突变与综合征性鱼鳞病相关，而缝隙连接变异显示出高度多效性，从掌跖角化病到角膜炎-鱼鳞病-耳聋综合征不等。黏附连接缺陷特异性地与少毛症相关。皮肤外受累，包括感音神经性听力损失和致心律失常性心肌病，成为若干连接综合征的关键哨兵特征。总之，儿童连接性遗传性皮肤病具有重叠的皮肤表现，但特定复合体决定了主要疾病机制。早期遗传学特征描述对于指导多学科监测危及生命的系统性合并症具有决定性意义。

英文摘要

Cellular junctions, including desmosomes, hemidesmosomes, adherens, tight, and gap junctions, are essential for epidermal integrity, barrier function, and cell signaling. Variants in genes encoding proteins involved in cellular junctions lead to a spectrum of skin disorders, commonly referred to as junctional genodermatoses, often presenting with phenotypic overlaps and multisystemic involvement in pediatric patients. This systematic scoping review aims to comprehensively map pediatric genodermatoses, correlating specific genetic variants with clinical manifestations to improve diagnostic and prognostic accuracy. A systematic literature review was conducted in PubMed, Web of Science, Embase and Scopus. The key terms included genetic skin disease and cellular junctions; case reports, case series, or observational studies of pediatric patients with skin diseases, specified junctional genes, and detailed clinical descriptions were considered. From 9,409 records, 159 studies were included, covering 25 key genes across five junctional complexes. Defects in anchoring complexes primarily manifested as skin fragility and blistering, including lethal neonatal forms of genodermatoses. Tight junction mutations were associated with syndromic ichthyoses, while gap junction variants showed high pleiotropy, ranging from palmoplantar keratoderma to keratitis-ichthyosis-deafness syndrome. Adherent junction defects were specifically associated with hypotrichosis. Extracutaneous involvement, including sensorineural hearing loss and arrhythmogenic cardiomyopathy, emerged as critical sentinel features in several junctional syndromes. In conclusion, pediatric junctional genodermatoses feature overlapping skin manifestations, but the specific complex dictates the primary disease mechanism. Early genetic characterization is determinant to guide multidisciplinary surveillance for life-threatening systemic comorbidities.