CLOVES综合征是一种罕见的过度生长综合征，临床表现复杂多样，以先天性脂肪过度生长、脉管畸形、表皮痣、骨骼畸形或脊柱侧弯或脊髓异常为主要特点。2017年5月广州市妇女儿童医疗中心介入血管瘤科收治1例CLOVES综合征患者，治疗效果较好。
一、病例介绍患儿女，6个月，因先天性右髂腰部肿物合并双足部畸形肿大入院。患儿出生第1天家属即发现其右髂腰部稍肿胀且存在表皮红斑，右脚趾明显粗大。此后，双脚趾逐渐增粗、增大，呈现宽三角足掌、巨趾、趾间距过宽外观。出生后3个月时，双侧足底开始增厚并局部凸起，左足部生长速度逐步超越右足。期间患儿无特殊不适，家属未予处理。就诊前2周，患儿右髂腰部肿物突然增大。入院后行B超检查示右髂腰部淋巴管畸形合并出血。进一步行MRI检查，提示右髂腰部皮下异常信号，考虑淋巴管畸形合并出血。双足X线片检查可见趾骨较同龄婴儿明显粗大，MRI检查提示双足部皮下脂肪异常增厚(图1)。因患儿符合先天性脂肪过度生长及脉管畸形特点，临床诊断为CLOVES综合征。进一步行全脊柱正、侧位及双下肢静脉B超检查，未见异常。本研究经广州市妇女儿童医疗中心伦理委员会批准(2016061605)，并与患者家属签署知情同意书。
点击查看大图
图1
A：患儿女，出生第1天，右髂腰部稍肿胀，局部可见片状红斑；B:患儿出生第1天，右脚脚趾明显膨大；C:患儿出生后6个月，双脚趾明显增粗增大，呈现宽三角足掌、巨趾、趾间距过宽；D:患儿出生后6个月，髂腰部肿物局部突发增大、变硬；E，F: MRI检查提示右侧髂腰部皮下弥漫团片状异常信号，T1WI呈等/稍低信号，T2WI压脂呈稍高信号，其内可见一囊性病灶，内见液液平面，下方液体T1WI及T2WI压脂均呈稍低信号；G: X线片提示双趾骨过度发育；H，I: MRI T2WI压脂成像提示右足和左足脂肪异常增生
Fig 1
A：On the first day of birth, the right iliolumbar region was slightly swollen with patchy erythema. B: On the first day of birth, the right toes were obviously enlarged. C: On the sixth month after birth, all toes were significantly enlarged, showing wide distance between toes. D: On the sixth month after birth, the local swelling in the iliolumbar region was suddenly worsened. E，F: MRI examination showed that the locus showed slightly high signal on T2WI and it had a cystic lesion with liquid-liquid level. G: X-ray showed that the phalanges excessively grew.H，I: MRI with T2WI compression imaging showed abnormal fat hyperplasia in the feet.
点击查看大图
图1
A：患儿女，出生第1天，右髂腰部稍肿胀，局部可见片状红斑；B:患儿出生第1天，右脚脚趾明显膨大；C:患儿出生后6个月，双脚趾明显增粗增大，呈现宽三角足掌、巨趾、趾间距过宽；D:患儿出生后6个月，髂腰部肿物局部突发增大、变硬；E，F: MRI检查提示右侧髂腰部皮下弥漫团片状异常信号，T1WI呈等/稍低信号，T2WI压脂呈稍高信号，其内可见一囊性病灶，内见液液平面，下方液体T1WI及T2WI压脂均呈稍低信号；G: X线片提示双趾骨过度发育；H，I: MRI T2WI压脂成像提示右足和左足脂肪异常增生
Fig 1
A：On the first day of birth, the right iliolumbar region was slightly swollen with patchy erythema. B: On the first day of birth, the right toes were obviously enlarged. C: On the sixth month after birth, all toes were significantly enlarged, showing wide distance between toes. D: On the sixth month after birth, the local swelling in the iliolumbar region was suddenly worsened. E，F: MRI examination showed that the locus showed slightly high signal on T2WI and it had a cystic lesion with liquid-liquid level. G: X-ray showed that the phalanges excessively grew.H，I: MRI with T2WI compression imaging showed abnormal fat hyperplasia in the feet.
二、治疗及随访入院当天予右髂腰部淋巴管畸形影像引导经皮硬化术，即在超声引导下多点、多角度经皮穿刺肿物，抽出暗红色不凝液体约13 ml后注入硬化剂4 mg(平阳霉素，吉林敖东药业集团延吉股份有限公司)，术后1个月复查B超提示右髂腰部肿块较前缩小80%(图2)。其后，因右髂腰部红斑行8次脉冲染料激光治疗(密度6～8 J/cm2，脉宽1.5 ms,光斑10 mm，DCD 30/20 ms)，每次间隔4周左右，颜色较治疗前明显变淡(图3)。硬化术后随访10个月，右髂腰部肿物未增大，双足部较同龄儿稍增大，但不影响患儿独立行走。
点击查看大图
图2
右腰部淋巴管瘤硬化治疗后1个月复查，B超检查提示病灶基本消退
图3
右髂腰部鲜红斑痣，经8次激光治疗后颜色明显较前变淡
Fig 2
B-ultrsonography showed that the lymphangioma on the right waist basically disappeared after sclerotherapy.
Fig 3
After 8 times of laser treatment, the color of port wine stains on the right waist was obviously lighter than before.
点击查看大图
图2
右腰部淋巴管瘤硬化治疗后1个月复查，B超检查提示病灶基本消退
图3
右髂腰部鲜红斑痣，经8次激光治疗后颜色明显较前变淡
Fig 2
B-ultrsonography showed that the lymphangioma on the right waist basically disappeared after sclerotherapy.
Fig 3
After 8 times of laser treatment, the color of port wine stains on the right waist was obviously lighter than before.
三、讨论CLOVES综合征较为罕见，目前美国登记在册的病例不足200例[1,2]。本例患儿表现为双足部脂肪增生、右髂腰部淋巴管畸形及出血、片状表皮红斑及双足部骨骼发育畸形，符合CLOVES综合征的特点，但目前尚未发现脊椎侧弯或脊髓异常。国外学者Alomari[3]曾报道18例CLOVES综合征患者中有6例存在脊柱侧弯，所以此例患儿今后仍需进一步监测脊柱发育情况。
CLOVES综合征的主要鉴别诊断为Proteus综合征。Proteus综合征是以出生后进行性发展、扭曲变形为特点的过度生长方式，故又称"变形综合征"[4]。而CLOVES综合征的增生往往为膨胀性的，同时合并以躯干为主的血管畸形、脂肪组织增生、骨结构肥大、脊柱侧弯，但无扭曲变形。研究认为，Proteus综合征病的病因为AKT1基因突变，而CLOVES综合征的病因为PIK3CA基因突变，必要时可行基因鉴定[5,6]。
CLOVES综合征无法彻底治愈，目前主要是对症处理，包括外科切除、硬化、介入栓塞等。其治疗是一个长期复杂的过程，需要多学科综合诊治，一般诊治越早，外观控制越好[7]。本例患儿行1次淋巴管畸形介入硬化治疗，8次红斑激光治疗，病情控制良好，但患儿双足部脂肪及骨骼仍在过度发育，鉴于暂不影响患儿生活质量，未行特殊处理，但不排除今后仍需进一步抽脂及对巨趾的矫正治疗。总之，本病长期预后不明，临床中还需积累更多的数据及病例以更好地认识本疾病。
