皮肤表皮痣是基因型多样的嵌合性疾病。 HRAS、KRAS 以及较少见的 NRAS 和 BRAF 中的致病性热点变异可能会导致孤立性角质形成细胞表皮痣和皮脂腺痣或与皮外异常相关的几种不同综合征。因此，一些作者提出了马赛克 RASopathies 的概念来对这些不同的疾病进行分组。在本文中，我们描述了由马赛克 HRAS 变异引起的综合征性表皮痣的三例新病例：一例与广泛的角化细胞表皮痣与乳房发育不全有关，另一例与广泛的粘膜受累有关第三种是小皮脂痣伴有癫痫发作和智力缺陷。此外，我们对所有综合征性表皮痣和相关疾病的病例进行了大量文献研究，并确认了 HRAS、KRAS、NRAS 或 BRAF 的致病性合子后变异。大多数患者出现骨骼、眼科或神经系统异常。横纹肌肉瘤、尿路上皮细胞癌和早青春期也屡有报道。 50%的病例涉及KRAS致病变异，尤其是皮脂腺痣、眼外胚层综合征和脑颅皮肤脂肪增多症。它们通常与眼睛和大脑异常有关。 HRAS 的致病变异在综合征性角质形成细胞性表皮痣和色素角化病中相当多。这篇综述描述了综合征性表皮痣与体细胞 RAS 和 BRAF 致病性变异的基因型/表型相关性，可能有助于改善他们的随访。© 作者（或他们的雇主）2024。禁止商业重复使用。请参阅权利和权限。由英国医学杂志出版。

Cutaneous epidermal nevi are genotypically diverse mosaic disorders. Pathogenic hotspot variants in HRAS, KRAS, and less frequently, NRAS and BRAF may cause isolated keratinocytic epidermal nevi and sebaceous nevi or several different syndromes when associated with extracutaneous anomalies. Therefore, some authors suggest the concept of mosaic RASopathies to group these different disorders.In this paper, we describe three new cases of syndromic epidermal nevi caused by mosaic HRAS variants: one associating an extensive keratinocytic epidermal nevus with hypomastia, another with extensive mucosal involvement and a third combining a small sebaceous nevus with seizures and intellectual deficiency. Moreover, we performed extensive literature of all cases of syndromic epidermal nevi and related disorders with confirmed pathogenic postzygotic variants in HRAS, KRAS, NRAS or BRAF.Most patients presented with bone, ophthalmological or neurological anomalies. Rhabdomyosarcoma, urothelial cell carcinoma and pubertas praecox are also repeatedly reported. KRAS pathogenic variants are involved in 50% of the cases, especially in sebaceous nevi, oculoectodermal syndrome and encephalocraniocutaneous lipomatosis. They are frequently associated with eye and brain anomalies. Pathogenic variants in HRAS are rather present in syndromic keratinocytic epidermal nevi and phacomatosis pigmentokeratotica.This review delineates genotype/phenotype correlations of syndromic epidermal nevi with somatic RAS and BRAF pathogenic variants and may help improve their follow-up.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.