CLOVES综合征的遗传学研究进展及相关疾病鉴别

Research Progress on the Genetics of CLOVES Syndrome and the Identification of Related Diseases

脉管畸形越来越多地被认为是由非遗传性体细胞突变引起的相关综合征。CLOVES综合征是一个相对比较新的临床术语,临床上以先天性脂肪瘤样过度生长(CLO)、脉管畸形(V)、表皮痣(E)和骨骼异常(S)为特征。Sapp等人在2007年首次描述,并由Alomari及其同事在2009年命名为CLOVES,其遗传学特征是由PIK3CA基因嵌合激活突变引起。这是一种进行性疾病,预后是可变的,取决于诊断时的年龄、解剖位置、血管畸形类型和整体健康状况。因此,早期正确的诊断显得很重要。由于其过度生长的侵袭性以及复发和毁容的可能性,手术治疗往往具有挑战性,而PIK3CA突变的确定使得靶向药物的开发成为当前治疗的崭新思路。本文综述了目前所知的这种罕见但具有挑战性的疾病的遗传学研究进展,并介绍其临床特征、鉴别诊断及治疗。

Vascular malformations are increasingly being identified as associated syndromes caused by sporadic, unheritable somatic mutations. CLOVES syndrome is a relatively new clinical term, characterized clinically by congenital lipomatous overgrowth (CLO), vascular malformations (V), epidermal nevi (E), and scoliosis/skeletal/spinal anomalies (S). First described by Sapp et al. in 2007 and named as CLOVES by Alomari and his colleagues in 2009, it was genetically characterized by mosaic activating mutation in gene PIK3CA. It is a progressive disease and the prognosis is variable depending on age at diagnosis, anatomic location, type of vascular malformation and overall health status. Therefore, an early and correct diagnosis appears to be important. Surgical treatment is often challenging due to its invasive nature of overgrowth and the possibility of recurrence and disfigurement, and the identification of PIK3CA mutations makes the development of targeted drugs a new idea for current therapies. This review summarizes the progress of the genetics of this rare but challenging disease, and introduces its clinical features, differential diagnosis and treatment.