王若光教授专题之［出生缺陷］（22）Poland序列征

病例来源

2016-12-1

遗传诊断大师们微信群

郭永新 道培医院

请教各位老师，哪位见过这样的症状？下图图片下缘是拇指，中间的手指没有骨头，指节缺乏，右侧胸肌缺如。

（点击上图可以放大查看）

贲进 昆明理工大学医学院

我对小指对称生长的多指发育缺陷比较熟，这种拇指对称生长（signaling pathway defects），手发育极性消失，posterior polarity（后极性）表现为anterior polarity（前极性），指节缺乏，我去查一下，表型很有意思！脚趾呢？

王若光 若光医学中心

双手都这样吗？还有其他表现吗？出生体重低吗？身高？面部特征？毛发稀疏吗？颅面有血管瘤吗？长骨短吗？

郭永新 道培医院

只是右手这样子，右侧胸肌缺如，其他都比较正常。

王若光 若光医学中心

好的，应该较清楚了，是Poland序列征，详细资料如下：

Poland序列征

（Poland syndrome）

一侧胸肌缺损，并指畸形

Poland序列征是一种少见但并非罕见的先天性畸形，又称胸大肌缺如短指并指综合征。它是由伦敦Guy’S医院的医学生Poland在1841年做尸体解剖时首先发现并报道了胸小肌和胸大肌胸骨段单侧缺损的个体，还伴有同侧手部表皮并指。1962年，同一医院的整形外科医生Clarkson遇到同样的病例，并将此先天畸形命名为Poland序列征。

Poland序列征的主要异常特征为胸部及乳头发育不良，皮下组织缺如，胸部重要肌肉部分缺如，肋骨软骨（第2～4或第3～5肋骨）发育不良或畸形，而同时又伴有腋下及乳房部分的脱毛症状和单侧的短指并指畸形。

目前发病原因不明，多认为是胚胎时期上肢发育障碍所致。具体的发病率报告较少，文献上多见散在病例的报道，一份来自巴西的研究新生儿肢体畸形的报告表明发病率约为1：30000。相较女性而言，男性发病率要较高一些，是女性的2～3倍。发病为右胸的情况占病例的60%～70%。在偶发病例和家族遗传比例之间存在着巨大的差异，就像其在不同人群中的差异一样大（男性和女性）。在偶发的Poland序列征病例中，男性发病数量占据绝大多数。对于男性，右胸发病几率要比左胸高两倍，但对于女性而言，左胸与右胸的发病几率几乎相同。据估计手部并指患者中，10%有Poland序列征。

常见异常

多样单侧特征如下：

1、胸部：胸大肌、乳头及乳晕发育不全甚至缺失，肋骨缺损。

在一些Poland序列征的病例中，胸部的病症情况会因其具体情况而有所不同。有的轻微发育不良，也有的肌肉组织完全缺如，而且在三分之一的女性患者身上都有出现乳头和乳晕部分发育不良且位置会更靠上，乳晕只是轻微着色甚至根本没有乳头和乳晕，此外，副乳也可能出现。患者的胸廓本身也许完全正常，然而，许多患者的胸腔都凹陷到一侧，这是由于发育不良的残损又细小的肋骨和软骨导致的。第2～4、3～5肋骨是最容易被影响的，在较靠前部分的肋骨发育不良，并伴有严重的胸腔凹陷，这种情况的发病率在11%～25%。胸部发育不良的肋骨末端也许会连接在一起，并且胸骨会向病变的一侧旋转，这种胸部病变的过程大多发生于其生长阶段。本病有显著表型差异性，包括两个先证者都为全Poland序列征的同胞，然而一个仅有胸肌缺如，另一个仅有并指畸形。独立的胸部发育不良是Poland序列征的一个变种，因为在一个家族病例中，一个成员也许会呈现单侧的胸部发育不良，而另一个成员也许会出现手和胸部都有缺陷的情况。没有手部缺陷的病例要多于表现完全的病例，这被称之为部分Poland序列征。据报告显示，轻微的Poland序列征病例发病率为1：16500。

2、上肢：远端发育不全伴不同程度的并指、短指、少指畸形，偶见严重缺损。

在Poland序列征中，手部的异常只发生在一边，并且其症状也有所不同。有手部呈蹼状的，也有短指并指的。和胸部缺陷相比，手部的缺陷几率要小，尽管手部的异常在Poland序列征中出现的几率约是13.5%～56%。大约有10%的指骨缺失患者也患有Poland序列征。在所有手指均发育不良的情况下，大拇指也会长出，只不过会不合比例的小，这种情况只会发生在大约10%的患者身上。

Poland序列征患者下肢出现先天畸形的病例非常罕见。

3、其他：偶发半椎体；肾脏畸形；先天性翼状肩胛畸形；肺疝；右位心。

肺疝在Poland序列征中的发病率约为8%。在这些患者身上，一些不正常的胸腔运动也许会对肺部的功能有着重要的临床意义。这些患者的心肺功能仅为正常人的48%，经过手术治疗后心肺功能可恢复至正常人的68%。患者如果出现了肺疝，X光片可显示出病变一侧的肺过于透明，同时心脏也有向健侧提升的趋势。

左侧Poland序列征患者显示孤立性右位心，但不伴有其他与同侧肋骨缺损相关的心血管缺损，在被报道的Poland序列征患者中看来是一种不可逆的心脏错位病症。孤立性右位心发病率大约是1：30000。在所有的这些患者中，Poland序列征始终发生在左侧并和肋骨缺陷联系在一起。据报道，在144例Poland序列征患者中，有5.6%的患者有右位心，他们中96%的人缺陷部位在身体左侧。这种相对高的数字说明也许右位心是Poland序列征的一部分，并且它可能由血管的生长所导致， 而并不是Poland序列征最初的状态。右位心呈高遗传率，尽管右位心通常会与心血管疾病联系起来，但在Poland序列征中并不是这样的。

自然病史

患儿身体其他方面均正常。

病因学

该病病因不清。Bouvet等根据受累侧血供减少提出原发性缺损可能是由于邻近锁骨下动脉发育不良，导致发育早期远端肢体及胸部供血不足，从而使这些区域的部分组织缺失。Bavinck和Weaver提出锁骨下动脉发育早期血流中断发生在离内部胸廓动脉较近的区域，而远离椎骨动脉区域。目前流行的理论是在怀孕的第6周结束时，当毗邻胸腔的上肢还处于生长阶段，由于胚胎供血的干扰导致了同侧的锁骨下动脉或它其中的一个分支发育不良，影响了血液流动的速度，血液流动减弱的程度决定了这种疾病的异常程度和严重性。胸部动脉发育不良会引发胸部主要肌肉组织缺如，而肱动脉发育不良会引发手部的畸形。另外的理论说，是由于中胚层侧面在受精后16至28天时的分裂所造成的缺陷。许多其他因素也被认为是Poland序列征的病因，如常染色体显性遗传、单个基因缺陷、外伤、病毒性感染、由于堕胎而作用于子宫的药物等。研究提示母亲吸烟可使发病风险增加两倍。

Poland序列征绝大多数的病例为散发，它在同一家系中再次发生的可能性小于1%，但也有几例报道有亲代到子代传递以及非患病亲代生出患病同胞。一篇关于一对女性双胞胎的典型Poland序列征病例说明了偶发情况下该序列征的特征。

注释

Bavinck和Weaver提出Poland、Moebius和Klippel-Feil序列征可以在同一个体发生各种各样组合，这几种序列征应根据相似的发育机制归为一类，构成一种涉及锁骨下动脉血流中断相关的序列征。这些症状是在发育的第6周由于锁骨下动脉、椎动脉或者其分支血供减少的结果，缺损模式依赖于血流减少的特定区域而定。

Poland序列征与Moebius序列征之间有很大的联系，那就是伴有眼部外展肌瘫痪的先天性面部神经性痉挛。有一种说法已经被提出，该说法认为导致Moebius序列征的原因是原始三叉神经动脉的过早退化，眼部外展肌瘫痪的先天性面部神经性痉挛，合并有胸部肌肉缺如及单侧手部缺陷构成了Poland-Moebious综合征。约有15%的Moebius序列征患者出现该种症状，并且在1973年这种疾病第一次被报道。在一些患有Poland序列征的病人身上，胸部上部的组织缺如造成肩胛上动脉中的血流量减少，可能会进一步造成肩胛骨的发育异常。

Poland序列征也会和Kippel-Feil序列征同时发生，Kippel-Feil序列征（系颈椎两节以上的先天性融合）的特点是病人的颈部较正常人短,又称短颈综合征、颈胸椎体先天性骨结合综合征、骨样斜颈综合征、先天性颈蹼综合征。临床以短颈、后发际低、颈部活动受限等三联征为特征。

Poland序列征在一定程度上也与肿瘤及白血病有一定联系。

治疗

1、胸腔凹陷

对于单侧胸腔凹陷并有进一步加重趋势，且缺少对心肺足够保护的患者，应该考虑手术治疗。胸部缺陷外科手术的治疗方案应根据患者的缺陷程度、年龄、性别而定。此外对于Poland综合征的患者一定要注意心脏的检查，如果异常要采取相应的措施，以防手术意外。

对于患有严重肋骨及胸腔凹陷的儿童，修复需要两个阶段。首先，肋骨的缺陷需要被修复。然后，进行肌肉的移植，这需要在儿童进入青春期前进行。对于症状较轻的Poland综合征儿童患者，当他们的症状仅限于胸部肌肉缺如或胸部发育不良时，手术需要延期至儿童进入青春期后。

对于成人而言，需要一个对胸腔稳定和重建的过程。在这个过程中，可以行自体移植。无论何时肋骨出现重大缺陷或肺疝，都应该用病变的肋骨，或自体组织，或网状补片，或以上几种的结合做移植来稳定胸腔。如果使用骨移植，中间的移植物应被缝合为一个中空的半个胸腔，一边的移植物应接合到新的肋骨末端的表面。骨移植物须用耐磨损的U形钉牢固定在上述部位。对于肋骨和软骨的重建不仅可以治愈缺陷，还可以防止了呼吸紊乱，并为肌肉移植提供了有力的支撑位置。如果使用网状补片，它需要被绷紧并且缝合于缺口的边缘。如果网状补片和骨移植都已被使用，网状补片还应被缝合于肋骨的移植物上。这样在病变一侧的肌肉和皮下组织缺失也许还会明显，这时再用胸部硅胶移植可提供必要的修复。有些患者缺口仅限于两根肋骨，但是正常的肋骨也会被分在缺口的上下两部分，并且会和缺陷的肋骨连在一起，引起胸腔的不合理运动。此时连接于胸骨末端的肋骨，它们都应该被分开，然后再连接在胸骨上。对于肋骨发育不良及前胸腔塌陷的患者而言，修复需要用网状补片来加强，以此来提高病变软骨的位置。手术时胸腔的旋转移位，也应同时被修复。

2、胸部发育不良

女性胸部发育不良及男性胸大肌发育不良时，如果患者无手术禁忌症且有治疗愿望，也应该行手术治疗。对于女性患者，可以用隆胸来修复胸部的发育不良，使用修补植入手法。手术应积极地修复胸部凹陷及腋前缘，再造出自然流畅的曲线。由于女性患者在乳房再造时需同时矫正胸部凹陷， 需要大量的组织， 因此应选用能提供足够组织量的肌瓣或皮瓣，如背阔肌皮瓣、腹直肌皮瓣、腹壁下动脉穿支皮瓣、臀大肌皮瓣等。其中，以背阔肌皮瓣较为常用，操作较简便，血供也较为可靠。必要时可联合应用乳房假体或扩张器的植入。这些要在患者进入成人期后完成，以此来调整两边乳房大小的一致性。对于男性患者的胸部凹陷，应用适量的自身软组织或植入体填充，即可获得较为满意的效果。

3、手指畸形

对于手指的并指短指畸形，主要是以改善手的功能为主，对于短指或手指发育短小一般不需特殊处理。并指畸形手指的分离要尽早完成，最好在一岁时做完，不要等到患儿出现异常行为或缺陷已经形成再分离。但是并指早期手术治疗有可能会术后复发，且手术时常因术野小，皮瓣成形、植皮及固定困难，术后易出现手指坏死、瘢痕挛缩、指蹼狭窄等并发症。所以大多数学者认为只要畸形不影响手部功能，手术应在学龄前（4～6岁）为宜。且多指并指畸形要分次手术进行。手术切口切忌呈纵向直线形，并指分离须至根部，否则会遗留部分并联。指蹼的重建对术后外形和功能的恢复十分重要，需重视术前设计。指蹼应占近节手指的1/3，指蹼皮瓣长为基底宽的两倍，宽度与邻指正常指蹼掌侧宽度相当。掌侧指蹼的基底应位于近节手指的1/3～1/2处，背侧皮瓣的基底应接近掌指关节，此指蹼具有正常长度、宽度和坡度。分指后的创面用全厚皮片或皮瓣修复为宜，不适合较薄断层皮片移植，这样可避免患儿生长发育时植皮侧与健侧生长不同步及皮片挛缩而致手指部分屈曲畸形。

分指术后早期正确功能锻炼极为重要。由于此时瘢痕尚未软化，外观较丑，患儿在解除固定后常不愿使用患手，加上怕痛，常会逃避锻炼。时间稍长，分开的手指就易屈曲挛缩，指蹼也会狭窄。因此，术后向患儿家长强调锻炼的重要性，介绍锻炼方法，鼓励患儿多用患手就显得十分重要。

对复发性并指再次手术后，除加强锻炼外，还可较长时间地使用夹板和指蹼间隔物。这些方法对防止瘢痕挛缩及促进功能恢复有一定辅助疗效。

坚持术后定期随访，早期1～2周复查一次，3个月后半年复查一次，至3～5年。这样可以制定随访锻炼计划，指导家长加强患儿手指各项功能练习，使并指治疗取得满意效果。

贲进 昆明理工大学医学院

赞同王教授。以下为英文检索结果：

Poland syndrome

（Poland's syndrome, Poland's syndactyly, Poland sequence,Poland's anomaly）

Poland syndrome is a rare birth defect characterized by underdevelopment or absence of the chest muscle (pectoralis) on one side of the body, and usually also webbing of the fingers (cutaneous syndactyly) of the hand on the same side (the ipsilateral hand). In most affected individuals, the missing part is the large section of the muscle that normally attaches to the upper arm on one side and the breastbone (sternum) on the other. Other abnormalities may occur on the affected side of the torso. In some cases, additional muscles in the chest wall, side, and shoulder are missing or underdeveloped.

There may also be rib cage abnormalities, such as shortened ribs, and the ribs may be noticeable due to less fat under the skin (subcutaneous fat). Breast and nipple abnormalities may also occur, and underarm (axillary) hair is sometimes sparse or abnormally placed. In most cases, the abnormalities in the chest area do not cause health problems or affect movement. Poland syndrome most often affects the right side of the body, and occurs more often in males than in females.

It is usually considered a unilateral condition. Some have claimed that the term can be applied in bilateral presentation, but others recommend using alternate terminology in those cases.

Signs and symptoms

Very frequent signs

1. Abnormal gastrointestinal tract

2. Absent pectoral muscles

（Male showing left pectoral absent）

3. Brachydactyly(Short fingers)

4. Dextrocardia

5. Diaphragmatic hernia/defect

6. Humerus absent/abnormal

7. Liver/biliary tract anomalies

8. Maternal diabetes

9. Oligodactyly/missing fingers

10. Radius absent/abnormal

11. Rhizomelic micromelia (relatively shorter proximal segment of the limbs compared to the middle and the distal segments)

12. Sparcity or abnormality of axillary hair on affected side

13. Syndactyly of fingers (webbing)

14. Ulna absent/abnormal

15. Upper limb asymmetry

16. Abnormal rib

17. Simian crease on affected side

Frequent signs

1. Hypoplastic/absent nipples

2. Scapula anomaly

Occasional signs

1. Agenesis/hypoplasia of kidneys

2. Encephalocele/exencephaly

3. Abnormal morphology of hypothalamic-hypophyseal axis

4. Abnormal function of hypothalamic-hypophyseal axis

5. Microcephaly

6. Preaxial polydactyly

7. Ureteric anomalies (reflux/duplex system)

8. Vertebral segmentation anomaly

Causes

The cause of Poland syndrome is unknown. However, an interruption of the embryonic blood supply to the arteries that lie under the collarbone (subclavian arteries) at about the 46th day of embryonic development is the prevailing theory.

The subclavian arteries normally supply blood to embryonic tissues that give rise to the chest wall and hand. Variations in the site and extent of the disruption may explain the range of signs and symptoms that occur in Poland syndrome. Abnormality of an embryonic structure called the apical ectodermal ridge, which helps direct early limb development, may also be involved in this disorder. Rare cases of Poland syndrome are thought to be caused by a genetic change that can be passed down in families, but no related genes have been identified.

Treatment

（Design of 3D custom made implant for Poland Syndrome）

（Man with Poland Syndrome / treated with 3D custom implant）

Technique

The complete or partial absence of the pectoralis muscle, is the malformation that defines Poland Syndrome. It can be treated by the insertion of a custom implant designed by CAD (computer aided design). A 3D reconstruction of the patient's chest is performed from a medical scanner, to design a virtual implant perfectly adapted to the anatomy of each one. The implant is made of medical silicone unbreakable rubber.

The Poland syndrome malformations being morphological, correction by custom implant is a first-line treatment. This technique allows a wide variety of patients to be treated with good outcomes. Poland Syndrome can be associated with bones, subcutaneous and mammary atrophy: if the first, as for pectus excavatum, is successfully corrected by a custom implant, the others can require surgical intervention such as lipofilling or silicone breast implant, in a second operation.

（Silicone custom made implant Poland Syndrome）

Surgery

The surgery takes place under general anaesthesia and lasts less than 1 hour. The surgeon prepares the locus to the size of the implant after performing a 8-cm axillary incision and inserts the implant beneath the skin. The closure is made in 2 planes.

The implant will replace the pectoralis major muscle, thus enabling the thorax to be symmetrical and, in women, the breast as well. If necessary, especially in the case of women, a second operation will complement the result by the implantation of a breast implant and/or lipofilling.

Surgical outcomes

Good surgical outcomes are easily achievable; the pain is treated with simple analgesics.

Minimal post-operative care: the stitches are resorbable, no drain is required, only a dressing for 8 days and a compression bra to wear from discharge for 15 days. Follow‑up consultation has to be done after 8 days. Sick leave is recommended for 15 days and playing sport can be resumed after 3 months.

Epidemiology

According to the National Human Genome Research Institute, Poland syndrome affects males three times as often as females and affects the right side of the body twice as often as the left.The incidence is estimated to range from one in 7,000 to one in 100,000 live births.

History

（Alfred Poland's original description of the syndrome.）

It was first named in 1962 by Patrick Clarkson, a New Zealand-born British plastic surgeon working at Guy's Hospital and Queen Mary's Hospital, London. He noticed that three of his patients had both a hand deformity and an underdeveloped breast on the same side. He discussed this with his colleague at Guy's Hospital, Dr Philip Evans, who agreed that the syndrome was "not widely appreciated". Clarkson found a reference to a similar deformity published byAlfred Poland, over a hundred years earlier in Guy's Hospital reports, in 1841. Clarkson was able to find the hand specimen dissected by Poland, which was still held in the hospital pathology museum.

Poland had dissected a convict known as George Elt, who was said to be unable to draw his hand across his chest. Poland noted the chest wall deformity, and this was illustrated in his article; the hand was also dissected and preserved for posterity in Guy's Hospital museum where it remains today. It cannot be truly said that Poland described this syndrome because he only described one isolated case. Clarkson published his series of three cases and named the syndrome after Poland in his article.

Notable cases

British TV presenter Jeremy Beadle (1948–2008) was known for having this condition. His Poland Syndrome manifested itself in the form of his disproportionately small right hand.

Olympic boxer Jérôme Thomas is also affected by Poland syndrome as his left arm and hand are significantly shorter and smaller than his right. Thomas also lacks a left pectoral muscle.

PGA Tour golfer Bryce Molder has Poland syndrome with an absent left pectoral muscle and a small left hand. Several surgeries in his childhood repaired syndactly on the left hand.

Actor Ted Danson, famous for starring in the TV show Cheers, admitted he had the condition in 2000 to Orange Coast magazine, and said that he was bullied as a child because of it.

Formula One World Champion Fernando Alonso is affected by Poland syndrome - he is missing the right pectoral muscle.

English cricketer Lewis Hatchett was born with Poland syndrome.

Researchers from the Department of Rehabilitation Medicine at the Yonsei University College of Medicine in Seoul, Korea reported a case of congenital absence of pectoralis major in 1990. According to Kakulas and Adams, pectoralis major is the most frequently congenitally absent muscle. The case involved a 22-year-old marine who had asymmetrical configuration of chest wall who had never experienced difficulties performing daily activities, but who experienced difficulties in the military camp. He had difficulty in some training activities especially those such as throwing a grenade or rope climbing.

特别鸣谢

昆明理工大学医学院 贲进教授