Congenital absence of skin (CAS) is a clinical sign associated with the main types of epidermolysis bullosa (EB). Very few studies have investigated the genetic background that may influence the occurrence of this condition. Our objective was to investigate genotype‐phenotype correlations on EB with CAS through a literature revision on the pathogenic variants previously reported. A total of 171 cases (49 EB simplex, EBS; 23 junctional EB, JEB; and 99 dystrophic EB, DEB), associated with 132 pathogenic variants in eight genes, were included in the genotype‐phenotype analysis. In EBS, CAS showed to be a recurrent clinical sign in EBS with pyloric atresia (PA) and EBS associated with kelch‐like protein 24; CAS was also described in patients with keratins 5/14 alterations, particularly involving severe phenotypes. In JEB, this is a common clinical sign in JEB with PA associated with premature termination codon variants and/or amino acid substitutions located in the extracellular domain of integrin α6β4 genes. In DEB with CAS, missense variants occurring close to non‐collagenous interruptions of the triple‐helix domain of collagen VII appear to influence this condition. This study is the largest review of patients with EB and CAS and expands the spectrum of known variants on this phenomenon.

中文翻译：

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先天性无皮肤大疱性表皮松解症的基因型-表型相关性：综合综述。

先天性皮肤缺失 (CAS) 是与大疱性表皮松解症 (EB) 主要类型相关的临床症状。很少有研究调查可能影响这种情况发生的遗传背景。我们的目标是通过对先前报告的致病变异的文献修订来研究 EB 与 CAS 的基因型 - 表型相关性。共有 171 例病例（49 例 EB 单纯型，EBS；23 例连接型 EB，JEB；和 99 例营养不良型 EB，DEB），与 8 个基因的 132 个致病变异相关，被纳入基因型-表型分析。在 EBS 中，CAS 显示为伴有幽门闭锁 (PA) 的 EBS 和与 kelch 样蛋白 24 相关的 EBS 的复发性临床体征；在角蛋白 5/14 改变的患者中也描述了 CAS，特别是涉及严重表型的患者。在 JEB，这是 JEB 的常见临床症状，PA 与位于整合素 α6β4 基因胞外域中的提前终止密码子变异和/或氨基酸取代相关。在带有 CAS 的 DEB 中，发生在胶原蛋白 VII 三螺旋结构域的非胶原性中断附近的错义变异似乎会影响这种情况。这项研究是对 EB 和 CAS 患者的最大规模审查，并扩展了这一现象的已知变异范围。