Öztürk Durmaz Emel, Demircioğlu Deniz, Yalınay Dikmen Pınar, Alanay Yasemin, Alanay Ahmet, Demirkesen Cüyan, Tokat Fatma, Karaarslan Ercan
Department of Dermatology, Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey.
Department of Neurology, Acıbadem Mehmet Ali Aydınlar University School of Medicine, İstanbul, Turkey.
Clin Cosmet Investig Dermatol. 2022 Apr 13;15:621-630. doi: 10.2147/CCID.S351637. eCollection 2022.
CLOVES syndrome is a novel sporadic mosaic segmental overgrowth syndrome, currently categorized under the canopy of PROS (-related overgrowth spectrum) disorders. All PROS disorders harbor heterozygous postzygotic activating somatic mutations involving the gene. As an upstream regulator of the signal transduction pathway, activating mutations of gene commence in uncontrolled growth of cutaneous, vascular (capillaries, veins, and lymphatics), adipose, neural, and musculoskeletal tissues. The excessive growth is segmental, patchy, asymmetric, and confined to body parts affected by the mutation. The term 'CLOVES' is an acronym denoting congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis) and/ or skeletal anomalies. The syndrome is characterized by an admixture of overgrown tissues, derived mainly from mesoderm and neuroectoderm. Among PROS disorders, CLOVES syndrome represents the extreme end of the spectrum with massive affection of almost the entire body. The syndrome might judiciously be treated with medications hampering with the signal transduction pathway. This article aims at reviewing the cutaneous and musculoskeletal manifestations of CLOVES syndrome, as the paradigm for PROS disorders. CLOVES syndrome and other PROS disorders are still misdiagnosed, underdiagnosed, underreported, and undertreated by the dermatology community.
CLOVES综合征是一种新型的散发性嵌合节段性过度生长综合征，目前归类于PROS（相关过度生长谱系）疾病范畴。所有PROS疾病都存在涉及该基因的杂合子合子后激活体细胞突变。作为信号转导通路的上游调节因子，该基因突变的激活始于皮肤、血管（毛细血管、静脉和淋巴管）、脂肪、神经和肌肉骨骼组织的不受控制的生长。过度生长是节段性的、斑片状的、不对称的，且局限于受突变影响的身体部位。“CLOVES”一词是一个首字母缩略词，代表先天性脂肪瘤样过度生长、血管畸形、表皮痣以及脊柱（脊柱侧弯）和/或骨骼异常。该综合征的特征是主要源自中胚层和神经外胚层的过度生长组织的混合。在PROS疾病中，CLOVES综合征代表了几乎累及全身的极端情况。该综合征可以明智地使用阻碍信号转导通路的药物进行治疗。本文旨在综述CLOVES综合征的皮肤和肌肉骨骼表现，作为PROS疾病的范例。CLOVES综合征和其他PROS疾病仍然被皮肤科界误诊、漏诊、报告不足和治疗不足。
