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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 69  |  Issue : 2  |  Page : 81-90

Association between the pectoral muscles and rib anomalies in poland syndrome


1 Department of Thoracic Surgery, School of Medicine, Mugla Sitki Koçman University, Mugla, Turkey
2 Department of Biostatistics, School of Medicine, Mugla Sitki Koçman University, Mugla, Turkey; School of Science, Siena College, New York, USA
3 Department of Anatomy, School of Medicine, Mugla Sitki Koçman University, Mugla, Turkey
4 Department of Chest Disease, Private Medical Park Hospital, Kocaeli, Turkey
5 Department of Thoracic Surgery, Private Medstar Hospital, Antalya, Turkey
6 Department of Thoracic Surgery, Dr. Suat Seren Chest Diseases and Surgery Training and Research Hospital, University of Health Sciences, Izmir, Turkey

Date of Submission14-Nov-2019
Date of Acceptance06-Feb-2020
Date of Web Publication30-Jun-2020

Correspondence Address:
Dr. Arife Zeybek
Department of Thoracic Surgery, School of Medicine, Mugla Sitki Koçman University, Mugla
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JASI.JASI_220_19

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  Abstract 


Introduction: The purpose of this study was to investigate the relationship between pectoralis major muscle (PMj) and rib defects in Poland syndrome (PS) and to evaluate the clinical findings and variabilities by the systematic review of all/current published articles on PS. Material and Methods: Based on our inclusion criteria, 86 patients were decided to be eligible for participating in this study. The data of the reviewed studies were classified according to the date of publication, age, sex, side of the deformity, defect type of PS, presence of other muscle or chest wall abnormalities, and dextrocardia. Further, other coexisting deformities and abnormalities were recorded. A logistic regression statistical analysis was carried out. Results: According to the reviewed cases, both left-sided presence-multiple muscle defects and left-sided presence-rib anomalies were found to be statistically significant (P = 0.007 and P = 0.04, respectively). The strength of the relationship between these two parameters was evaluated by binary logistic regression analysis, which revealed that multiple muscle defects and rib anomalies were associated with left chest side presence (P = 0.005 and P = 0.02, respectively). When the relationship between rib anomalies and PMj defect was analyzed, the association was found to be statistically significant (P = 0.03). Furthermore, the result of the strength analysis was also supported this association (P = 0.04). Discussion and Conclusion: Molecular and embryological development processes of the ribs and pectoral muscles are investigated to assess the presence of a structural relationship considering the causal connection between ribs and PMj in PS. As a supportive element to our study, the presence of a myogenic regulatory factor–Hox gene link was asserted in the animal experiments done by some researchers, showing a common development process of the rib and pectoral muscle. We believe that with the outcomes of this study, the clinical diversity and the etiopathogenesis of PS could be explained comprehensively.

Keywords: Hox gene, myogenesis, myogenic regulatory factor 5, Poland syndrome, sclerotome


How to cite this article:
Zeybek A, Tosun K, Gencer CU, Kalemci S, Öz N, Çalışkan S, Bozdaǧ HG. Association between the pectoral muscles and rib anomalies in poland syndrome. J Anat Soc India 2020;69:81-90

How to cite this URL:
Zeybek A, Tosun K, Gencer CU, Kalemci S, Öz N, Çalışkan S, Bozdaǧ HG. Association between the pectoral muscles and rib anomalies in poland syndrome. J Anat Soc India [serial online] 2020 [cited 2020 Jul 3];69:81-90. Available from: http://www.jasi.org.in/text.asp?2020/69/2/81/288672




  Introduction Top


Poland syndrome (PS) is a rare congenital disorder that typically presents itself with the absence of the costosternal part of pectoralis major muscle (PMj) and ipsilateral brachysyndactyly of the upper limb.[1] Other commonly seen abnormalities in PS are skeletal malformations of the thoracic wall and breast anomalies. Dextrocardia, lung herniation, liver herniation, kidney anomalies and tumors, and other skeletal defects have also been described in rare cases.[2],[3],[4],[5],[6] Episodes of transient compression to the flow of the subclavian artery during the embryonic period are generally accepted etiopathogenesis of PS.[3] Unfortunately, this etiopathological approach is insufficient to explain the clinical variants and findings in PS. This clinical diversity has brought along some questions about the etiology, diagnosis, and treatment of this disorder, and this approach could do no consensus or an accurate classification. In this study, we attempted to explain the pathogenesis of PS by investigating its association with the clinical outcomes of other comorbidities and aimed to evaluate this syndrome in an etiopathological point of view through a systemic review of case reports.


  Material and Methods Top


A systematic literature search was performed. Web of Science, PubMed, Medline, and Google Scholar databases were employed for the studies on PS. The Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines were followed while conducting this study [Appendix A]. The systematic review protocol was registered in the PROSPERO (CRD42017069888). The search strategies used are listed in Appendix B. The eligibility criteria were established before the data gathering from the full-text articles, including thorax computed tomography, published in Medline, Web of Science, PubMed Publisher, and Google Scholar databases.

The article screening for inclusion was carried out by two reviewers (M.A and R.Ö.B). The needed data regarding the characteristics and outcomes of the studies were collected independently by the reviewers through a standardized extraction table. Based on our inclusion criteria, 86 patients were included in our study. From the patient population of our clinic, two cases were selected to be eligible for this study [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]. The data from the included studies were categorized according to the name of publication, year of publication, age, sex, side of the deformity, defect type of PS, presence of other muscle or chest wall abnormalities, and dextrocardia.
Figure 1: The absence of anterior costal ribs observed with an inspection in an adult patient

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Figure 2: Dextrocardia was observed in the chest X-ray of the adult patient

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Figure 3: Total absence of left pectoral major muscle were observed by computed tomography

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Figure 4: Total rib defects were observed in the pediatric patient's radiographs

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Figure 5: Three-dimensional tomographic scan of the child's thorax skeletal structure

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The frequency of the disease, the correlation among chosen variables, and the significance of the results were statistically analyzed. The statistical significance was assessed with Fisher's exact test using the logistic regression method. The results were considered statistically significant when P < 0.05.


  Results Top


A total of 3544 articles related to PS were reported in the Medline, Web of Science, PubMed, and Google Scholar databases. Based on our inclusion criteria, 86 patients were included in our study [Flow Chart 1].



Patient demographics were as follows: 74.4% of the patients (n = 64) were male, 25.6% (n = 22) were female, and their age ranged between 11 and 30 years (50%, n = 43). Other accompanying findings in the patients with PS were defined as 51.2% (n = 42) extremity malformation, 87.9% (n = 67) breast and nipple anomalies, and 26.7% (n = 23) dextrocardia with situs solitus. Overall clinical findings of the patients are given in [Table 1].
Table 1: Overall clinical findings of the patients

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PS was more frequent in male subjects (74.4%) than in female subjects (25.6%), with a ratio of 3:1. Right hemithorax involvement was present in 42 (50%) patients. Sixty-seven of the 86 patients had the complete defect, while 17 patients had the partial defect of the PMj. Other muscle anomalies accompanying PMj defect have also been reported in various studies, and the number of patients with this specification was 41 in our study. The pectoral minor muscle (PMi) defect was one of the most frequently observed other concomitant muscle defects. Muscle defects are divided into two categories according to the involvement of other muscle deficiencies. Presence of other muscular defects, besides PMj defect, is named as multiple muscle defect. The correlation between the left side and multiple muscle defects was found to be statistically significant, P = 0.007. The strength of the relationship between these two parameters was evaluated by binary logistic regression analysis, which revealed that multiple muscle defect was associated with left chest side, P = 0.005 [Table 2].
Table 2: Statistical analyses

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Rib anomalies were detected in 50 patients (58.1%), and the mean value for deficient ribs was found as 2. The cases were divided into two groups according to the number of deficient ribs: one groups have number of deficient ribs more than two and other group have number of deficient ribs equal to and fewer than two. The left-sided presentation and rib anomalies were found to be significant, P = 0.04.

The presence of dextrocardia was found in 22 of 50 patients with rib anomalies, and the analysis supported the relationship between these variables [OR = 0.036, 95% confidence interval, 0.005–0.287 P = 0.002, [Table 2].

Rib anomalies were mostly detected in patients with a complete absence of PMj (P = 0.03), and the association between the variables is shown in Table 3 (P = 0.04).


  Discussion Top


PS was first described by Alfred Poland in 1841. Other commonly used definitions could be listed as Poland sequence, Poland's anomaly, and Poland's syndactyly. Classical PS is characterized by hypoplasia or partial absence of the sternocostal head of PMj and ipsilateral brachysyndactyly.[1]

While the majority of PS cases are sporadic, there are documented cases of inheritability which display an autosomal dominant inheritance pattern with incomplete penetrance. A wide range of frequencies from 1/30,000 to 1–9/100,000 has been estimated.[2],[3],[18]

Males are more commonly affected than females, with a 3:1 ratio. In 75% of the cases, the right side of the chest is involved. However, in our study, we investigated the severity of the combination of rib anomaly and PMj defect on the left side of the thorax.

During our review, other pathological components such as rib defect, upper or lower limb hypoplasia/aplasia, digital structure, digital webbing, cardiac anomalies, nipple and axillary hair anomalies, diaphragmatic hernia or eventration, gonadal chromosomal anomalies such as turner syndrome, central nervous system and vertebral anomalies, liver and kidney anomalies, skin-related diseases, lack of subcutaneous fat tissue, hematologic disorders, optic lens anomalies, and urogenital tumors were reported in various studies.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72],[73],[74],[75],[76],[77],[78],[79],[80],[81],[82],[83]

According to the results of our study, rib anomalies were commonly associated with left-sided involvement, and it is supported by the study of Torre et al.[84] However, the real cause behind this fact is not fully explained, such as the etiology of PS.

For explaining the pathogenesis of PS, the most commonly accepted theory is the vascular injury during the 6th week of embryogenesis due to an interruption to the blood flow in the branches of subclavian and vertebral arteries when the pectoralis muscle is developing. Other possible causes could be listed as teratogens, intrauterine trauma, infections, and malformation of lateral plate mesoderm.[2],[3],[18]

The main criterion for the diagnosis of PS is aplasia or hypoplasia of PMj. Moreover, in addition to the PMj anomaly, other muscular anomalies such as PMi, serratus anterior, trapezius, latissimus dorsi, external oblique, and peroneal muscle defects were reported in studies.[4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34],[35],[36],[37],[38],[39],[40],[41],[42],[43],[44],[45],[46],[47],[48],[49],[50],[51],[52],[53],[54],[55],[56],[57],[58],[59],[60],[61],[62],[63],[64],[65],[66],[67],[68],[69],[70],[71],[72],[73],[74],[75],[76],[77],[78],[79],[80],[81],[82],[83]

In this study, it is observed that the incidence for the presentation of multiple muscle anomalies with left hemithorax involvement is significantly high. Binary logistic regression analysis is used for the evaluation. To explain this close relationship between rib anomalies and PMj defect, structural relationship and molecular and embryological development process of chest wall had been searched.

A common pathway during the development process of both pectoral muscle and skeletal structure of the chest wall is reported in the results of animal experimentations of some studies.[85],[86],[87] As generally known, pectoral muscles originate from hypaxial myotome, while ribs develop from sclerotome. Furthermore, the myogenic regulatory factor 5 (Myf 5) gene is responsible for the development of the pectoral muscle, and the Hox gene is responsible for the development of ribs. Interestingly, the placement of the Hox protein receptors is suggested to be in the hypaxial myotome instead of sclerotome. It has been reported that the rib development in the thoracic vertebral levels was triggered by the activation of the Hox 6 gene through regulation of the Myf5/Myf6 gene expression in the hypaxial myotome. The information is transmitted to the sclerotome through platelet-derived growth factor-alpha subunit, and fibroblast growth factor 4 signaling by a cell nonautonomous mechanism had been asserted.[87] This reported Myf-Hox gene link is upheld with the results of our study.


  Conclusion Top


In light of these results, this study that we have conducted would be beneficial for explaining the clinical diversity and, even more importantly, the etiopathogenesis of PS. Investigating the role of Myf5 by advanced genetic research may enlighten the etiopathogenesis of many diseases concerning the thoracic wall anomalies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.


  Appendix Top


Appendix A: Preferred Reporting Items for Systematic Review and Meta.Analysis 2009 Checklist



From: Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6 (7):e1000097. doi: 10.1371/journal.pmed1000097. For more information, visit: www.prisma-statement.org.


  Appendix B: Search Strategy Top


PubMed Publication

((((“Poland Syndrome/analysis”[Mesh] OR “Poland Syndrome/anatomy and histology”[Mesh] OR “Poland Syndrome/blood”[Mesh])) AND (“Poland Syndrome/chemically induced”[Mesh] OR “Poland Syndrome/classification”[Mesh] OR “Poland Syndrome/complications”[Mesh] OR “Poland Syndrome/congenital”[Mesh] OR “Poland Syndrome/diagnosis”[Mesh] OR “Poland Syndrome/diagnostic imaging”[Mesh] OR “Poland Syndrome/embryology”[Mesh] OR “Poland Syndrome/epidemiology”[Mesh] OR “Poland Syndrome/etiology”[Mesh] OR “Poland Syndrome/genetics”[Mesh] OR “Poland Syndrome/history”[Mesh] OR “Poland Syndrome/pathology”[Mesh] OR “Poland Syndrome/physiology”[Mesh] OR “Poland Syndrome/physiopathology”[Mesh] OR “Poland Syndrome/surgery”[Mesh] OR “Poland Syndrome/therapy”[Mesh])) AND (“Pectoralis Muscles/abnormalities”[Mesh] OR “Pectoralis Muscles/analysis”[Mesh] OR “Pectoralis Muscles/anatomy and histology”[Mesh] OR “Pectoralis Muscles/blood supply”[Mesh] OR “Pectoralis Muscles/chemistry”[Mesh] OR “Pectoralis Muscles/diagnosis”[Mesh] OR “Pectoralis Muscles/diagnostic imaging”[Mesh] OR “Pectoralis Muscles/drug effects”[Mesh] OR “Pectoralis Muscles/embryology”[Mesh] OR “Pectoralis Muscles/etiology”[Mesh] OR “Pectoralis Muscles/growth and development”[Mesh] OR “Pectoralis Muscles/pathology”[Mesh])) AND (“Bone Diseases, Developmental/analysis”[Mesh] OR “Bone Diseases, Developmental/anatomy and histology”[Mesh] OR “Bone Diseases, Developmental/classification”[Mesh] OR “Bone Diseases, Developmental/congenital”[Mesh] OR “Bone Diseases, Developmental/embryology”[Mesh] OR “Bone Diseases, Developmental/genetics”[Mesh] OR “Bone Diseases, Developmental/history”[Mesh] OR “Bone Diseases, Developmental/surgery”[Mesh])

Medline

((((“Poland Syndrome/analysis”[Mesh] OR “Poland Syndrome/anatomy and histology”[Mesh] OR “Poland Syndrome/blood”[Mesh])) AND (“Poland Syndrome/chemically induced” OR “Poland Syndrome/classification” OR “Poland Syndrome/complications”[Mesh] OR “Poland Syndrome/congenital”[Mesh] OR “Poland Syndrome/diagnosis”[Mesh] OR “Poland Syndrome/diagnostic imaging”[Mesh] OR “Poland Syndrome/embryology”[Mesh] OR “Poland Syndrome/epidemiology”[Mesh] OR “Poland Syndrome/etiology”[Mesh] OR “Poland Syndrome/genetics” OR “Poland Syndrome/history”[Mesh] OR “Poland Syndrome/pathology”[Mesh] OR “Poland Syndrome/physiology”[Mesh] OR “Poland Syndrome/physiopathology”[Mesh] OR “Poland Syndrome/surgery”[Mesh] OR “Poland Syndrome/therapy”[Mesh])) AND (“Pectoralis Muscles/abnormalities”[Mesh] OR “Pectoralis Muscles/analysis”[Mesh] OR “Pectoralis Muscles/anatomy and histology”[Mesh] OR “Pectoralis Muscles/blood supply”[Mesh] OR “Pectoralis Muscles/chemistry”[Mesh] OR “Pectoralis Muscles/diagnosis '' OR “Pectoralis Muscles/diagnostic imaging”[Mesh] OR “Pectoralis Muscles/drug effects”[Mesh] OR “Pectoralis Muscles/embryology”[Mesh] OR “Pectoralis Muscles/etiology”[Mesh] OR “Pectoralis Muscles/growth and development”[Mesh] OR “Pectoralis Muscles/pathology”)) AND (“Bone Diseases, Developmental/analysis”[Mesh] OR “Bone Diseases, Developmental/anatomy and histology”[Mesh] OR “Bone Diseases, Developmental/classification”[Mesh] OR “Bone Diseases, Developmental/congenital”[Mesh] OR “Bone Diseases, Developmental/embryology”[Mesh] OR “Bone Diseases, Developmental/genetics”[Mesh] OR “Bone Diseases, Developmental/history”[Mesh] OR “Bone Diseases, Developmental/surgery”)

Web of Science

(“Poland Syndrome/analysis” OR “Poland Syndrome/anatomy and histology” OR “Poland Syndrome/blood”)) AND (“Poland Syndrome/chemically induced” OR “Poland Syndrome/classification” OR “Poland Syndrome/complications” OR “Poland Syndrome/congenital” OR “Poland Syndrome/diagnosis” OR “Poland Syndrome/diagnostic imaging” OR “Poland Syndrome/embryology” OR “Poland Syndrome/epidemiology” OR “Poland Syndrome/etiology” OR “Poland Syndrome/genetics” OR “Poland Syndrome/history” OR “Poland Syndrome/pathology” OR “Poland Syndrome/physiology” OR “Poland Syndrome/physiopathology” OR “Poland Syndrome/surgery” OR “Poland Syndrome/therapy”)) AND (“Pectoralis Muscles/abnormalities” OR “Pectoralis Muscles/analysis” OR “Pectoralis Muscles/anatomy and histology” OR “Pectoralis Muscles/blood supply” OR “Pectoralis Muscles/chemistry” OR “Pectoralis Muscles/diagnosis”OR “Pectoralis Muscles/diagnostic imaging” OR “Pectoralis Muscles/drug effects” OR “Pectoralis Muscles/embryology” OR “Pectoralis Muscles/etiology” OR “Pectoralis Muscles/growth and development” OR “Pectoralis Muscles/pathology”)) AND (“Bone Diseases, Developmental/analysis” OR “Bone Diseases, Developmental/anatomy and histology” OR “Bone Diseases, Developmental/classification” OR “Bone Diseases, Developmental/congenital” OR “Bone Diseases, Developmental/embryology” OR “Bone Diseases, Developmental/genetics” OR “Bone Diseases, Developmental/history” OR “Bone Diseases, Developmental/surgery”)

Google Scholar

Poland Syndrome, Poland Syndrome classification, Poland Syndrome congenital, Poland Syndrome diagnosis, Poland Syndrome diagnostic imaging, Poland Syndrome epidemiology, Poland Syndrome etiology, Poland Syndrome genetics, Pectoralis Muscles/abnormalities, Pectoralis Muscles/anatomy and histology Pectoralis Muscles embryology, Pectoralis Muscles etiology, Pectoralis Muscles/growth and development, Bone Diseases, Developmental/anatomy and histology, Poland Syndrome pathology.

Supplementary Data


  Poland Syndrome Top


Case 1

A 29-year-old male patient was accepted to our outpatient clinic with blunt trauma to the right side of the chest. After a physical examination and radiological evaluations, no trauma-related complications on the right side of the chest were detected; however, an asymmetry in the left chest wall, an upward-positioned nipple at the left side, and collapsed left chest wall and abdomen were noted. When palpated, the absence of costal cartilage of the 5th–10th rib on the left chest wall and muscle weakness on the chest wall and anterior abdominal wall were identified, and a 20 cm × 15 cm area of hypopigmentation on the left chest wall – the area that was separated by a sharp border on the same level as the skin was noted [Figure 1]. No pathological findings or symptoms were found in the rest of the physical examination. There was no paradoxical respiration or dyspnea in the patient. Respiratory reserves were found to be within normal limits.

On the thoracic computed tomographic (CT) scan, total agenesis of the left pectoralis major muscle (PMj), pectoralis minor muscle hypoplasia, left rectus abdominis xiphoid adnexa head aplasia, and left 5th–10th costal cartilage defects were detected. These findings implied Poland syndrome (PS) and accompanying dextrocardia [Figure 2] and [Figure 3]. No congenital heart disease was detected by echocardiographic evaluation performed by a cardiologist. No decrease or change in the arterial bloodstream was reported in the upper left extremity or left subclavian arterial Doppler ultrasonography (USG). A moderate level of hepatosplenomegaly was noted in the abdominal USG. There was no abnormality in the vertebral or skeletal structure. In addition, the patient had no family history of PS.

Case 2

A 6-year-old boy was referred to our outpatient clinic with a preliminary diagnosis of chest wall deformity. Our examination confirmed a deformity in the left chest wall and shoulder, while respiratory and cardiac assessments indicated normal results. In the upper left extremity, the hyperabduction was limited and the left scapula was located in an upward position, the muscle structure in the left chest wall was weak, and two nipples on that side were positioned upward [Figure 4].

According to the chest X-ray, abdominal USG, the thoracic magnetic resonance imaging and CT, the left third and fourth ribs had total agenesis, and the fifth and sixth ribs showed fusion with the vertebrocostal joint and had anterior defects; the patient was described with aplasia of the left PMj muscles and the serratus anterior, and his scapula was directed upward. The patient had a 15° thoracic scoliosis facing the left at the first lumbar vertebra and distal diastematomyelia, which was determined to be in a 5-mm confined area [Figure 5].



 
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    Figures

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    Tables

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  In this article
Abstract
Introduction
Material and Methods
Results
Discussion
Conclusion
Appendix
Appendix B: Sear...
Poland Syndrome
References
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