Reinforcing the vascular disruption theory of the genesis of Poland’s syndrome: a rare association of diaphragmatic eventration in a preterm infant with severe musculoskeletal defects
- Nadira Shahrul Baharin 1,
- Eman Awadh Hashim 1 , 2,
- Quek Bin Huey 1 , 3 , 4 and
- Suresh Chandran 1 , 3 , 4 , 5
- 1 Neonatology, KK Women's and Children's Hospital, Singapore
- 2 Neonatology, Salmanya Medical Complex, Kingdom of Bahrain, Bahrain
- 3 Neonatology, NUS Yong Loo Lin School of Medicine, Singapore
- 4 Neonatology, Duke NUS Medical School, Singapore
- 5 Neonatology, Lee Kong Chian School of Medicine, Singapore
- Correspondence to Professor Suresh Chandran; profschandran2019@gmail.com
Abstract
A preterm female infant was admitted at birth with respiratory distress. On examination, she had an asymmetric right chest wall and ipsilateral small hand. Air entry was reduced over the right chest. A clinical diagnosis of Poland’s syndrome was made based on the hypoplasia of the right pectoral muscles, absent nipple, deformed ribs and symbrachydactyly of the ipsilateral hand. Chest X-ray suggested and ultrasound confirmed eventration of the right hemidiaphragm. ‘Subclavian artery supply disruption sequence’ (SASDS) theory by Bavnick and Weaver remains the most accepted pathogenic mechanism in Poland’s syndrome. This case reinforces SASDS theory associated with the genesis of Poland’s syndrome that relates to the pathogenicity of vascular disruption of subclavian artery, characteristics of which are unilateral pectoral defects, symbrachydactyly and eventration of the diaphragm. At 2 months, she underwent diaphragm plication. She is under review by our multidisciplinary surgical team for reconstruction of the chest deformity.
Background
Poland’s syndrome (PS) was first described in 1841 by Alfred Poland based on a postmortem finding of the absence of the pectoralis major with ipsilateral syndactyly of the hand.1 However, 36 years before Poland, Citizen Marandel (1803) described a woman with mammary absence in addition to pectoral muscular atrophy, while Froriep, in 1839, described a case of pectoral muscle absence and digital webbing.2 3 Dr Clarkson of Guy’s Hospital, London compiled the associated anomalies and termed it as ‘Poland’s syndactyly’ in 1962.4 Later, it was Baudinne who introduced the term Poland’s syndrome instead of Poland’s syndactyly.5 Eponymous origin of PS remains a debate to date.
PS is a rare anomaly.6 PS constitutes not only musculoskeletal hypoplasia but also multisystem involvement including dextrocardia, lung herniation, renal, vertebral, pelvis and lower limb malformations.7 8 Most cases of PS are sporadic but there are familial cases with intrafamilial phenotypic variability.9 Current evidence favours the theory of disruption of the development of subclavian artery and/or its branches during the embryonic period in the pathogenesis of PS.10
Case presentation
We present a female infant who was born at 34 weeks’ gestation with a birth weight of 2100 g. Antenatal scan at 21 weeks of gestation was normal. Maternal medical and obstetric histories were unremarkable. Parents were non-consanguineous, and examination of the parents did not reveal any stigmata of PS. Despite tocolysis, labour progressed, and she was delivered via emergency caesarean section. At birth, the baby had respiratory distress with significant chest retractions, more so in the right side of the chest than the left. She was transferred to neonatal intensive care unit for continuous positive airway pressure (CPAP) support.
On examination, the infant had hollow chest with pectoral hypoplasia, absent nipple and reduced air entry over the right side of the chest. The right hand and fingers appeared smaller than the left with partial syndactyly of the middle, ring and little fingers, and normal forearms. There was no facial dysmorphism or extra digital malformations in other limbs. Cardiac examination revealed a systolic murmur over the precordium, and abdominal examination was unremarkable. There was no scoliosis or asymmetry of the lower limbs.
On her review at 10 months of age, in addition to right symbrachydactyly, she was noted to have reduced right shoulder bulk and limited external rotation of the shoulder. There was also reduced supination and pronation of the right forearm. A clinical diagnosis of Sprengel’s deformity was made.
Investigations
This infant underwent detailed imaging to identify the deformities. Chest radiograph showed asymmetric thoracic cage and deformed right chest ribs, with eventration of the right dome of the diaphragm (EOD) (figure 1). An ultrasound of the diaphragm showed a superior bulge of the anterior aspect of the right diaphragm with reduced movement of 2 mm during phases of respiration. In comparison, the posterior aspect demonstrated a movement of 7 mm, consistent with congenital EOD (video 1). The left hemidiaphragm showed normal movement of 14 mm (video 2). Paediatric surgeons involved in the management of the infant favoured conservative care. Echocardiography showed normal cardiac situs and a large patent ductus arteriosus (PDA) of 4.3 mm with a predominantly left to right flow with no volume overload of left heart. Pulmonary pressure was marginally high.
Chest X-ray shows evidence of right-sided diaphragmatic eventration (long arrow) that was subsequently confirmed on us. Deformed right-sided ribs can be seen (short arrow).
Differential diagnosis
Differential diagnosis includes chest wall defects, nipple/breast anomalies, isolated thoracic lipoatrophy and unilateral limb defects without pectoralis major muscle involvement.
Rarely, Moebius and Klippel-Feil syndromes are associated with PS.
Treatment
She was subjected to surgical intervention at chronological age of 2 months. Intraoperative findings revealed right hemidiaphragm eventration and large PDA, 4 mm. PDA ligation and right hemidiaphragm plication were successfully carried out. She required home CPAP up to 1 year of age with regular follow-up by a multidisciplinary team.
Outcome and follow-up
The infant was last reviewed at 2 years of age and noted to have marked asymmetry of the right chest, restricted movement of the arm and shoulder blade, and hypoplasia of the right hand. For fine motor skills, she is unable to use both hands together. Using the right hand, she can pick a ball and throw on the floor, is able to use spoon for feeding and scribbles with a pen. Fine motor skills for her left hand is normal. She relates well with her peers. She is being reviewed for reconstructive procedures of the right chest wall by the surgical team.
Discussion
We present a case of PS with hypoplasia of right chest wall, ipsilateral symbrachydactyly, EOD and Sprengel’s deformity. We previously reported a rare case of PS in a neonate with lung herniation.8
Incidence of PS ranges from around 1:17 000 live births in Japan to 1 in 52 530 live births in Hungary. PS occurs in men with a predominance of 3:1 ratio, and right side is more affected than the left in 75% of the cases.11 12
The aetiology of PS is still debated. Several theories and aetiological factors have been suggested with the vascular disruption theory being the most accepted to date. The pathogenic hypothesis of subclavian artery supply disruption sequence (SASDS), introduced by Bavinck and Weaver, points to an insult variably interrupting the blood supply to the subclavian artery, resulting in the underdevelopment of the pectoral muscles in the embryo along with a range of associated hand anomalies.10 The theory suggests that an insult, likely hypoxic in nature, takes place between 6th and 7th weeks of gestation, at a time the aortic arch revolutionises into the arterial system.11 13 Other factors causing PS include maternal smoking and cocaine abuse.14 In our case, neither parents have the stigmata nor a family history of PS, supporting the sporadic origin. However, genetic predisposition to PS has been proposed by various researchers.15 Association of PS with congenital hyperinsulinism in a neonate with duplication of the short arm chromosome 10 and phenotypic defects of PS in monozygotic twins with a de novo mutation of chromosome 11q12.3 are indicators of genetic aetiology.16 17 Familial cases with intrafamilial variability and their possible paradominant inheritance have been reported.16 These genetic associations may be a step to future antenatal screening for the cause of PS.
The characteristic features of PS is a combination of pectoral hypoplasia and symbrachydactyly of the ipsilateral hand. A wide spectrum of the syndrome with different associations has been reported.18 Patients with PS can have hypoplasia of pectoralis minor, latissimus dorsi, deltoid muscle, serratus anterior muscle, supraspinatus and infraspinatus muscles. Breast hypoplasia to amastia has been reported in female patients, in addition to areolar and axillary hypoplasia.12 Chest wall defects do not only affect the muscles, but also extend to the thoracic cage with hypoplasia/forked or absence of ribs, scoliosis and severe hemithorax deformities causing poor lung function, as observed in our case.19 The incidence of rib defects in PS is 18% on the right side, compared with 40% on the left side.20
Hypoplasia of the upper limb involves hand and wrist (89%), forearm (37%), arm (7%) and rarely phocomelia.21 The limb anomalies seen in PS have a wide spectrum of presentation, ranging from completely normal hand, to deformities such as syndactyly, polydactyly, brachysyndactyly and symbrachydactyly. Ipsilateral syndactyly occurs in 66% of patients with PS, middle three fingers being most commonly affected.22 Disruption of internal iliac artery was described in a woman with right thoracic musculoskeletal defects having ipsilateral hypoplasia of the gluteal muscle and ilium.23 Bilateral PS with absence of both breasts with severe right pectoral deficiency and absent right radius and ulnar side of the hand was reported.24
Involvement of scapula in PS has been described. Sprengel’s deformity, due to hypoplasia or absence of serratus anterior muscle, occurs in 15% of patients with PS.18 Obstruction of blood flow in subclavian, internal thoracic and/or suprascapular arteries could cause muscle defect and hypoplasia of the scapula.10 It is characterised by malposition and dysplasia of the scapula that is caused by failed migration of the scapula during early embryonic life.25 Our case has limitation of movements of the right shoulder.
To the best of our knowledge, ours is the third reported case of EOD in PS. This makes it a rare entity but notable when investigating a newborn infant having subtle stigmatas of PS with respiratory symptoms. Congenital EOD is a developmental defect of part or entire muscular portion of the diaphragm, where the diaphragmatic muscle is replaced by fibroelastic tissue, loosening its attachment to ribs, sternum and spine, causing the weak hemidiaphragm to move into the thorax. The diaphragm is supplied in the embryonic phase by pericardiophrenic and musculophrenic branches of the internal thoracic artery, branch of the first part of subclavian artery.19 This supports SASDS theory in our case as the child has defects involving right hemithorax, absent nipple, ipsilateral hand and hemidiaphragm, all involved with disruption of right subclavian artery. Often patients with isolated EOD are asymptomatic and diagnosed on chest X-ray incidentally. Diagnosis of EOD is by using X-ray/ultrasound/CT of the chest, as noted in our case. There is no specific timing for the repair of EOD as most cases can be asymptomatic and could resolve by appropriate ventilation support. The indication for diaphragm plication is usually if patients are symptomatic requiring ventilatory support for more than 2 weeks.26 In PS with additional rib and marked musculoskeletal defects, infants can be increasingly symptomatic needing early surgical intervention. In our case, diaphragmatic plication was delayed until the baby reached term and optimal weight.
Other congenital anomalies found to be associated with PS include dextrocardia, craniofacial dysplasia, neurofibromatosis, microcephaly, hypoplastic kidney, coagulation disturbance, non-Hodgkin’s lymphoma and congenital hyperinsulinaemia.12 17
PS can be diagnosed clinically at birth if the distinctive features of unilateral chest hypoplasia and ipsilateral limb defects are present. Regardless, many cases are diagnosed at various ages and sometimes presented to medical care for reports not related to the PS itself. We can attribute this diverse diagnosis time to the wide spectrum of variation of severity of presentations, especially in those patients having milder pectoral defects with normal hands.
Imaging modalities are crucial in PS to identify the specific location and characteristics of chest wall deformity. The chest radiograph is the first and most basic study, which usually shows lung field hyperlucency in the affected side. Both CT and MRI are used to enable accurate diagnosis, to show the extent of lesions in the musculoskeletal component, and to help the surgeon’s decision-making regarding the best modalities for reconstruction.27
Antenatal diagnosis of PS by ultrasound scan has been reported in fetuses having severe chest wall defects between 12th and 13th week of gestation. In such cases, fetal diagnosis helps in perinatal counselling. If parents decide to terminate the pregnancy, autopsy of the abortus is crucial to confirm the diagnosis.28
From infancy, multidisciplinary involvement is vital. This is essential to help refine a child’s growth and development, specifically gross and fine motor developmental skills. Some may have functional disability of the affected hand, especially in puberty. Surgical intervention is usually delayed to adolescence, as the correction is mostly for cosmetic reasons with the exception if the patient presents with severe respiratory symptoms that require earlier intervention. Some believe that delaying the intervention is better as the patient will be involved in the decision-making regarding the correction, and also to avoid surgical revision to keep up with growth.27 29
There are different surgical techniques used in chest wall reconstruction, it depends on the severity of the defect and also the gender of the patient. The most used techniques are the latissimus dorsi flap, or the rectus abdominal flap if the latissimus dorsi is absent as a part of the syndrome.29 Successful restoration of the pectoralis muscle mass by injections of adipose-derived mesenchymal stem cells and fat transfer has been reported.30 Novel chest reconstruction modalities include lipofilling or lipo-modelling technique, which uses fat grafts, aided by three-dimensional (3D) computer-aided design, has yielded high-quality cosmetic results exceeding 90%.31
Conclusions
PS has a wide spectrum of presentations. Even though the aetiopathogenesis of PS is still debated, vascular disruption theory stands good in our case with manifestations restricting to involvement of all regional areas supplied by the right subclavian artery, which includes right upper limb, pectoral muscles and rib hypoplasia, EOD and Sprengel’s deformity. Association of congenital EOD with PS is rare and the infant in our case was symptomatic from birth needing an early intervention. Usually cases can be missed in infancy as the presentation might be subtle and widely variable. PS is a clinical diagnosis but needs detailed imaging such as 3D CT to precisely identify the musculoskeletal defects aiding surgeons in reconstruction. With the current available evidence, PS remains a sporadic disorder, an information useful for genetic counselling. Overall, the outcome of PS is favourable except in rare cases like ours which require early surgical intervention due to EOD causing respiratory compromise.
Learning points
-
We encourage clinicians to have strong suspicion of Poland’s syndrome (PS) when asymmetrical chest wall in association with hand anomalies is noted in newborn infants.
-
Basic radiographs are useful to detect bony defects and ultrasound helps to diagnose eventration of diaphragm or lung herniation. Three-dimensional CT scan is ideal to identify muscles precisely before reconstruction surgeries.
-
Generally, outcome and prognosis of PS are favourable. Modes of disability are usually limb defects. Therefore, early multidisciplinary involvement is important.
-
PS is sporadic, and to date, the theory of subclavian artery disruption sequence is the most accepted in the pathogenesis of PS.
-
Antenatal diagnosis may be the future of PS. It can be detected if there is bony deformity over the chest wall and/or with severe limb defects.
Acknowledgments
The authors would like to thank A/Professor Teo Eu-leong Harvey James, Department of Diagnostic Imaging, for providing the images/videos and legends for this case report and Professor Divakaran Liginlal (Carnegie Mellon University, Pittsburgh, Pennsylvania, USA) for language editing of the manuscript.
Footnotes
-
Contributors NSB and EAH: manuscript preparation and review of literature. SC and QBH: review and editing of the final manuscript.
-
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
-
Competing interests None declared.
-
Patient consent for publication Parental/guardian consent obtained.
-
Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
Use of this content is subject to our disclaimer