{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:52:15Z","timestamp":1791471135333,"version":"4.3.4"},"reference-count":120,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Pectus excavatum (PE) is the most common deformity of the chest wall and is characterized by the posterior depression of the sternum and the lower costal cartilages. To date, the etiology of PE in humans remains enigmatic. Several etiologic hypotheses have been proposed over the past two centuries. However, most of them have been scientifically dismissed and now have only historic value. In this systematic review, we assess scientific publications of the past two centuries addressing the issue of the origin of PE in humans. We present and discuss the histologic, genetic, biomechanical, and experimental scientific achievements that contributed to the clarification of its etiology and pathogenesis. With no clear consensus over the exact mechanism, most recent studies agree that the primordial defect leading the deformation of the anterior chest wall in PE is related to the costal hyaline cartilage structure and function. Further studies on this subject must be carried out. Genetic studies seem to be the most promising way to understand the exact mechanism of PE\u2019s origin and pathogenesis.<\/jats:p>","DOI":"10.3390\/jcm11051241","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T21:11:07Z","timestamp":1645737067000},"page":"1241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Current Concepts in the Etiology and Pathogenesis of Pectus Excavatum in Humans\u2014A Systematic Review"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4295-7487","authenticated-orcid":false,"given":"Vlad Laurentiu","family":"David","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery and Orthopedics, \u201cVictor Babes\u201d University of Medicine and Pharmacy, 2 Eftimie Murgu, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1053\/j.sempedsurg.2008.03.002","article-title":"Pectus excavatum: Historical background, clinical picture, preoperative evaluation and criteria for operation","volume":"17","author":"Kelly","year":"2008","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1093\/icvts\/ivs045","article-title":"Pectus excavatum: History, hypotheses and treatment options","volume":"14","author":"Brochhausen","year":"2012","journal-title":"Interact. Cardiovasc. Thorac. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0022-3468(88)80629-8","article-title":"Surgical repair of pectus excavatum","volume":"23","author":"Shamberger","year":"1988","journal-title":"J. Pediatr. Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"493","DOI":"10.21037\/acs.2016.06.04","article-title":"Pectus excavatum from a pediatric surgeon\u2019s perspective","volume":"5","author":"Nuss","year":"2016","journal-title":"Ann. Cardiothorac. Surg."},{"key":"ref_5","first-page":"203","article-title":"Preliminary results after Nuss procedure","volume":"105","author":"Nicodin","year":"2010","journal-title":"Chirurgia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"136","DOI":"10.21823\/2311-2905-2013--2-136-141","article-title":"Etiology and pathogenesis of pectus excavatum in children","volume":"19","author":"Kulik","year":"2013","journal-title":"Traumatol. Orthop. Russ."},{"key":"ref_7","first-page":"63","article-title":"Funnel chest (pectus excavatum) in 10\u201316th century fossil material","volume":"13","author":"Toth","year":"2001","journal-title":"J. Paleontol."},{"key":"ref_8","unstructured":"Bauhinus, J. (1609). Observatio. Ioannis Schenckii a Grafenberg, De partibus Vitalibus, Thorace Contentis. Johannes Observatorium Medicarum, Rararum, Novar-um, Admirabilium, et Montrosarum, Liber Secundus."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/BF02230501","article-title":"Eine seltene Mi\u00dfbildung des Thorax","volume":"49","author":"Eggel","year":"1870","journal-title":"Virchows. Arch. Path Anat."},{"key":"ref_10","first-page":"515","article-title":"Untersuchungen \u00fcber den mi\u00dfbildeten Brustkorb des","volume":"49","author":"Langer","year":"1880","journal-title":"Herrn. JW Wien. Med. Zeit"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/BF01926731","article-title":"Ueber eine seltene Missbildung des Thorax","volume":"57","author":"Flesch","year":"1873","journal-title":"Virchow. Arch. Path Anat."},{"key":"ref_12","unstructured":"Hagmann (1888). Selten vorkommende Abnormit\u00e4t des Brustkastens. J. B Kinderheilkd., 15, 455."},{"key":"ref_13","first-page":"1563","article-title":"Zur chirurgischen Behandlung der angeborenen Trichterbrust","volume":"48","author":"Meyer","year":"1911","journal-title":"Berl. Klin. Wschr."},{"key":"ref_14","unstructured":"Muller, C. (1906). Zur Entwicklung des Menschlichen Brustkorbs, Morphol Jahrb, W Engelman."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0096-5588(20)32070-5","article-title":"Chonechondrosternon: Report of a case and review of the Iiterature","volume":"8","author":"Ochsner","year":"1938","journal-title":"J. Tboracic. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1097\/00000658-191003000-00015","article-title":"Surgical Diseases of Children: A Modern Treatise on Pediatric Surgery","volume":"51","author":"Kelley","year":"1910","journal-title":"Ann. Surg."},{"key":"ref_17","first-page":"174","article-title":"Funnel chest (pectus excavatum) in infancy and adult life","volume":"74","author":"Brown","year":"1951","journal-title":"Calif. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1055\/s-0028-1113633","article-title":"Untersuchungen zur Pathogenese der Brustkorbverformungen1","volume":"84","author":"Maneke","year":"1959","journal-title":"DMW Dtsch. Med. Wochenschr."},{"key":"ref_19","first-page":"624","article-title":"\u00dcber erbliche Arachnodaktylie","volume":"9","author":"Curschmann","year":"1936","journal-title":"Nervenarzt"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Saxena, A.K. (2017). History of Surgical Repairs of Chest Wall Deformities in Saxena AK editor. Chest Wall Deformities, Springer.","DOI":"10.1007\/978-3-662-53088-7"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S0096-5588(20)32033-X","article-title":"Pectus Excavatum","volume":"9","author":"Brown","year":"1939","journal-title":"J. Thorac. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S0096-5588(20)32033-X","article-title":"Lincoln: Pectus Excavatum (Funnel Chest). Anatomic Basis: Surgical Treatment of the Incipient Stage in In-fancy; and Correction of the Deformity in the Fully Developed Stage","volume":"9","author":"Brown","year":"1940","journal-title":"J. Thorac. Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1378\/chest.19.3.288","article-title":"Congenital chondrosternal depression (funnel chest) Its treatment by phrenosternolysis and chondroster-noplasty","volume":"19","author":"Brodkin","year":"1951","journal-title":"Dis. Chest."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1378\/chest.24.3.259","article-title":"Congenital Anterior Chest Wall Deformities of Diaphragmatic Origin","volume":"24","author":"Brodkin","year":"1953","journal-title":"Dis. Chest"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/0002-9610(59)90488-X","article-title":"Pectus excavatum: Surgical experiences in thirty-four cases","volume":"98","author":"Jackson","year":"1959","journal-title":"Am. J. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1097\/00000658-194904000-00002","article-title":"The Operative Treatment of Pectus Excavatum","volume":"129","author":"Ravitch","year":"1949","journal-title":"Ann. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0022-3476(50)80026-4","article-title":"Funnel chest: Its cause, effects, and treatment","volume":"37","author":"Lester","year":"1950","journal-title":"J. Pediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0039-6109(16)35047-2","article-title":"The Management of Pectus Excavatum","volume":"36","author":"Koop","year":"1956","journal-title":"Surg. Clin. N. Am."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1097\/00000658-194406000-00012","article-title":"Pectus Excavatum: Report of Two Cases Successfully Operated Upon","volume":"119","author":"Sweet","year":"1944","journal-title":"Ann. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1097\/00000658-195510000-00009","article-title":"Considerations in the Surgical Treatment of Pectus Excavatum","volume":"142","author":"Lindskog","year":"1955","journal-title":"Ann. Surg."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1001\/archsurg.1953.01260040324003","article-title":"Surgical treatment of the congenital funnel-chest deformity","volume":"67","author":"Mahoney","year":"1953","journal-title":"AMA Arch. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/bjs.1800540209","article-title":"Observations on the aetiology of pectus excavatum and other chest deformities, and a method of recording them","volume":"54","author":"Mullard","year":"1967","journal-title":"Br. J. Surg."},{"key":"ref_33","unstructured":"Sauerbruch, F. (1920). Die Chirurgie Der Brustorgane, Julius Springer."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S0022-3468(98)90314-1","article-title":"A 10-year review of a minimally invasive technique for the correction of pectus excavatum","volume":"33","author":"Nuss","year":"1998","journal-title":"J. Pediatr. Surg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0022-3468(79)80258-4","article-title":"Cosmetic improvement of thoracic wall defects using a rapid setting silastic mold: A special technique","volume":"14","author":"Allen","year":"1979","journal-title":"J. Pediatr. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1136\/adc.32.161.5","article-title":"The operative treatment of the funnel chest","volume":"32","author":"Rehbein","year":"1957","journal-title":"Arch. Dis. Child."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0096-5588(20)30116-1","article-title":"Satisfactory surgical correction of pectus excavatum deformity in childhood; a limited opportunity","volume":"36","author":"Welch","year":"1958","journal-title":"J. Thorac. Surg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/S0022-3468(87)80585-7","article-title":"Use of CT scans in selection of patients for pectus excavatum surgery: A preliminary report","volume":"22","author":"Haller","year":"1987","journal-title":"J. Pediatr Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s00268-008-9793-4","article-title":"912 Open Pectus Excavatum Repairs: Changing Trends, Lessons Learned: One Surgeon\u2019s Experience","volume":"33","author":"Fonkalsrud","year":"2008","journal-title":"World J. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.jtcvs.2007.06.008","article-title":"Valuable lessons from two decades of pectus repair with the Willital-Hegemann procedure","volume":"134","author":"Saxena","year":"2007","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_41","first-page":"358","article-title":"Surgical correction of the funnel chest \u201csternoturnover\u201d","volume":"69","author":"Wada","year":"1961","journal-title":"West. J. Surg. Obstet. Gynecol."},{"key":"ref_42","first-page":"361","article-title":"A new method of surgical treatment of funnel chest with help of permanent magnets","volume":"21","author":"Isakov","year":"1980","journal-title":"Chir. Pediatr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jpedsurg.2006.09.042","article-title":"Magnetic mini-mover procedure for pectus excavatum: I. Development, design, and simulations for feasibility and safety","volume":"42","author":"Harrison","year":"2007","journal-title":"J. Pediatr. Surg."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1586\/17434440.4.3.283","article-title":"Magnet-mediated thoracic remodeling: A new approach to the sunken chest","volume":"4","author":"Jamshidi","year":"2007","journal-title":"Expert Rev. Med. Devices"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/j.jpedsurg.2017.03.009","article-title":"Magnetic Mini-Mover Procedure for pectus excavatum IV: FDA sponsored multicenter trial","volume":"52","author":"Graves","year":"2017","journal-title":"J. Pediatr. Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1055\/s-2006-956178","article-title":"Die \u201cneue\u201d Erlanger Trichterbrustkorrektur\u2014Minimalisierung eines bew\u00e4hrten Verfahrens [The \u201cnew\u201d Erlangen technique of funnel chest correction\u2014minimalization of a well working procedure]","volume":"131","author":"Weber","year":"2006","journal-title":"Zentralbl. Chir."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"5736","DOI":"10.21037\/jtd.2018.09.148","article-title":"Elastic stable chest repair and its hybrid variants in 86 patients with pectus excavatum","volume":"10","author":"Luber","year":"2018","journal-title":"J. Thorac. Dis."},{"key":"ref_48","first-page":"306","article-title":"Pectus deformities","volume":"94","author":"Giem","year":"1961","journal-title":"Calif. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0096-5588(20)30366-4","article-title":"The etiology and pathogenesis of funnel chest, pigeon breast, and related deformities of the anterior chest wall","volume":"34","author":"Lester","year":"1957","journal-title":"J. Thorac. Surg."},{"key":"ref_50","unstructured":"Cormack, D.H. (2001). Essential Histology, Lippincott Williams &Wilkins. [2nd ed.]."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1007\/BF02659333","article-title":"Biochemical, morphological and physical as well as animal ex-perimental studies on the pathogenesis of funnel chest","volume":"319","author":"Geisbe","year":"1967","journal-title":"Langenbecks Arch. Chir."},{"key":"ref_52","first-page":"164","article-title":"Morphological studies on resected rib cartilage in funnel chest","volume":"76","author":"Flach","year":"1967","journal-title":"Frankf. Z. Fur Pathol."},{"key":"ref_53","first-page":"13","article-title":"The aetiology and pathogenesis of funnel chest","volume":"3","author":"Geisbe","year":"1971","journal-title":"Prog. Pediatr. Surg."},{"key":"ref_54","first-page":"65","article-title":"Morphologische Ver\u00e4nderungen der Rippenknorpel bei Trichterbrust (Morphologic changes of rib cartilages in funnel chest)","volume":"15","author":"Tischer","year":"1968","journal-title":"Beitr. Orthop. Traumatol."},{"key":"ref_55","first-page":"228","article-title":"Pathogenesis of chest wall abnormalities\u2014electron microscopy studies and trace element analysis of rib cartilage","volume":"42","author":"Rupprecht","year":"1987","journal-title":"Zeitschrift Kinderchirurgie"},{"key":"ref_56","first-page":"20","article-title":"Pathohistology of costal cartilage and immunomorphologic characteristics of collagen in funnel chest","volume":"49","author":"Kuritsyn","year":"1987","journal-title":"Arkhiv. Patol."},{"key":"ref_57","first-page":"314","article-title":"Light microscopic studies of the cartilage in funnel chest. A new view of the pathogenesis","volume":"22","author":"Rupprecht","year":"1989","journal-title":"Z. Exp. Chir. Transpl. Kunstl. Organe"},{"key":"ref_58","first-page":"91","article-title":"Changes in the structure of type I collagen and cross-links between type I and type III collagen chains in a patient with funnel chest","volume":"35","author":"Sokolov","year":"1989","journal-title":"Vopr. Med. Khim."},{"key":"ref_59","first-page":"90","article-title":"Structural charac-teristics of collagens from the skin and rib cartilage of patients with Ehlers-Danlos syndrome type II","volume":"36","author":"Sokolov","year":"1990","journal-title":"Vopr. Med. Khim."},{"key":"ref_60","first-page":"71","article-title":"Extractability of collagen from the rib cartilage and skin in funnel chest in children","volume":"34","author":"Tsvetkova","year":"1988","journal-title":"Vopr. Med. Khim."},{"key":"ref_61","first-page":"53","article-title":"The effect of ascorbic acid on the collagen synthesis in skin fibroblasts of children with funnel chest","volume":"36","author":"Tsvetkova","year":"1990","journal-title":"Vopr. Med. Khim."},{"key":"ref_62","first-page":"576","article-title":"Characterization of Costal Cartilage Collagen in Funnel Chest","volume":"2","author":"Prozorovskaya","year":"1991","journal-title":"Biomed. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"177","DOI":"10.3109\/03008209409061970","article-title":"Analysis of collagen hydroxypyridinium crosslinks in samples of tissues and urine of patients with inherited connective tissue disorders","volume":"30","author":"Borisova","year":"1994","journal-title":"Connect. Tissue Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1007\/BF00784192","article-title":"Analysis of hydroxypyri-dine cross-links of collagen from human rib cartilage","volume":"115","author":"Borisova","year":"1993","journal-title":"Biull. Eksp. Biol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1053\/jpsu.2001.28820","article-title":"The biomechanical, morphologic, and histochem-ical properties of the costal cartilages in children with pectus excavatum","volume":"36","author":"Feng","year":"2001","journal-title":"J. Pediatr. Surg."},{"key":"ref_66","first-page":"207","article-title":"40-year experience in surgical treatment of congenital chest deformationsethio\u2013pathogenesis, operative techniques and clinical results","volume":"70","author":"Serafin","year":"2003","journal-title":"Acta Chir. Orthop. Traumatol. Cech."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1053\/j.semtcvs.2009.03.001","article-title":"Anatomical, histologic, and genetic characteristics of congeni-tal chest wall deformities","volume":"21","author":"Fokin","year":"2009","journal-title":"Semin. Thorac. Cardiovasc. Surg."},{"key":"ref_68","first-page":"625","article-title":"Morphologic, morphometrical and histochemical pro-prieties of the costal cartilage in children with pectus excavatum","volume":"52","author":"David","year":"2011","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1002\/ar.22824","article-title":"Rib Cartilage Characterization in Patients Affected by Pectus Excavatum","volume":"296","author":"Tocchioni","year":"2013","journal-title":"Anat. Rec. Adv. Integr. Anat. Evol. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8","DOI":"10.17116\/patol2018800518","article-title":"Costal cartilage changes in children with pectus excavatum and pectus carinatum","volume":"80","author":"Kurkov","year":"2018","journal-title":"Arkhiv. Patol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Kurkov, A., Guller, A., Fayzullin, A., Fayzullina, N., Plyakin, V., Kotova, S., Timashev, P., Frolova, A., Kurtak, N., and Pau-kov, V. (2021). Amianthoid transformation of costal cartilage matrix in children with pectus excavatum and pec-tus carinatum. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0245159"},{"key":"ref_72","first-page":"40","article-title":"Ultrastructural changes of child rib cartilage in different deformations of chest cells","volume":"64","author":"Shamik","year":"2001","journal-title":"Arkhiv. Patologii"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1113\/expphysiol.1996.sp003956","article-title":"The cellular physiology of articular cartilage","volume":"81","author":"Hall","year":"1996","journal-title":"Exp. Physiol."},{"key":"ref_74","first-page":"69","article-title":"Deformities of the chest","volume":"4","author":"Coulson","year":"1820","journal-title":"Lond. Med. Gaz."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0140-6736(47)90629-6","article-title":"Congenital Funnel Chest","volume":"250","author":"Sainsbury","year":"1947","journal-title":"Lancet"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/BF02230501","article-title":"Eine seltene Missbildung des Thorax","volume":"49","author":"Eggel","year":"1870","journal-title":"Virchow\u2019s Archiv."},{"key":"ref_77","first-page":"50","article-title":"Congenital malformation of the thorax: Great depression of the sternum","volume":"24","author":"Williams","year":"1872","journal-title":"Trans. Path Soc."},{"key":"ref_78","unstructured":"Grunenthal, A. (1888). Ueber Trichterbrust, Inaug. Diss."},{"key":"ref_79","first-page":"308","article-title":"Zur Kasuistik der Trichterbrust","volume":"41","author":"Herbst","year":"1887","journal-title":"Deutsch. Arch. Klin. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1016\/j.jpedsurg.2006.05.071","article-title":"Family study of the inheritance of pectus excavatum","volume":"41","author":"Creswick","year":"2006","journal-title":"J. Pediatr. Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.admecli.2004.06.002","article-title":"Chest wall anomalies: Pectus excavatum and pectus carinatum","volume":"15","author":"Goretsky","year":"2004","journal-title":"Adolesc. Med. Clin."},{"key":"ref_82","first-page":"161","article-title":"Advancing our understanding of the inheritance and transmission of pectus excavatum","volume":"1","author":"Horth","year":"2012","journal-title":"J. Pediatr. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1016\/j.jpedsurg.2009.07.029","article-title":"Etiology of chest wall deformities\u2014A genetic review for the treating physician","volume":"44","author":"Kotzot","year":"2009","journal-title":"J. Pediatr. Surg."},{"key":"ref_84","unstructured":"Adam, M.P., Ardinger, H.H., and Pagon, R.A. (1993\u20132022). Marfan Syndrome, University of Washington. GeneReviews\u00ae [Internet]."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/jmg.2009.072785","article-title":"The revised Ghent nosology for the Marfan syndrome","volume":"47","author":"Loeys","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1136\/hrt.32.2.241","article-title":"Familial skeletal cardiovascular syndrome (Holt-Oram) in a polygamous African family","volume":"32","author":"Antia","year":"1970","journal-title":"Heart"},{"key":"ref_87","unstructured":"Adam, M.P., Ardinger, H.H., and Pagon, R.A. (1993\u20132020). Noonan Syndrome, University of Washington."},{"key":"ref_88","unstructured":"Miklovic, T., and Sieg, V.C. (2021). Ehlers Danlos Syndrome, StatPearls Publishing."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1053\/j.sempedsurg.2018.05.007","article-title":"Poland syndrome: A proposed classification system and perspectives on diagnosis and treatment","volume":"27","author":"Romanini","year":"2018","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1002\/ajmg.1320230405","article-title":"Subclavian artery supply disruption sequence: Hypothesis of a vascular etiology for Poland, Klippel-Feil, and M\u00f6bius anomalies","volume":"23","author":"Bavinck","year":"1986","journal-title":"Am. J. Med. Genet."},{"key":"ref_91","first-page":"19","article-title":"Identifying heritable connective tissue disorders in childhood","volume":"256","author":"Armon","year":"2012","journal-title":"Practitioner"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"E94","DOI":"10.1097\/BRS.0b013e31818b88a5","article-title":"Genetic linkage localizes an adolescent idiopathic scoliosis and pectus excavatum gene to chromosome 18 q","volume":"34","author":"Gurnett","year":"2009","journal-title":"Spine"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1093\/hmg\/ddv170","article-title":"Gpr126\/Adgrg6 deletion in cartilage models idiopathic scoliosis and pectus excavatum in mice","volume":"24","author":"Karner","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1124\/pr.114.009647","article-title":"International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein\u2013Coupled Receptors","volume":"67","author":"Hamann","year":"2015","journal-title":"Pharmacol. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"ra76","DOI":"10.1126\/scisignal.2005347","article-title":"Type IV collagen is an activating ligand for the adhesion G protein\u2013coupled receptor GPR126","volume":"7","author":"Paavola","year":"2014","journal-title":"Sci. Signal."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/ng.122","article-title":"Many sequence variants affecting diversity of adult human height","volume":"40","author":"Gudbjartsson","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"25697","DOI":"10.1074\/jbc.M101558200","article-title":"Molecular cloning and characterization of a novel human galactose 3-O-sulfotransferase that transfers sulfate to gal beta 1\u2014>3galNAc residue in O-glycans","volume":"276","author":"Seko","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1038\/cr.2012.149","article-title":"Evidence for GAL3ST4 mutation as the potential cause of pectus excavatum","volume":"22","author":"Wu","year":"2012","journal-title":"Cell Res."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1096\/fasebj.3.9.2663581","article-title":"Structure and biology of cartilage and bone matrix noncollagenous macromolecules","volume":"3","author":"Oldberg","year":"1989","journal-title":"FASEB J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"109557","DOI":"10.1016\/j.mehy.2020.109557","article-title":"TINAG mutation as a genetic cause of pectus excavatum","volume":"137","author":"Tong","year":"2020","journal-title":"Med. Hypotheses"},{"key":"ref_101","unstructured":"TINAG (2021, December 12). Tubulointerstitial Nephritis Antigen, Available online: https:\/\/www.ncbi.nlm.nih.gov\/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=27283."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1353\/hub.2007.0026","article-title":"Search for hand osteoar-thritis susceptibility locus on chromosome 6p12.3-p12.1","volume":"79","author":"Jakowlev","year":"2007","journal-title":"Hum. Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/S0011-3840(96)80005-0","article-title":"Congenital chest wall deformities","volume":"33","author":"Shamberger","year":"1996","journal-title":"Curr. Probl. Surg."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1093\/ejcts\/ezw195","article-title":"Growth and pectus excavatum: Is there a relation?","volume":"50","author":"Pilegaard","year":"2016","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_105","unstructured":"Holder, T.M. (1986). Chest Wall Deformities in Ashcraft KW, Saunders Compmany. [2nd ed.]."},{"key":"ref_106","unstructured":"Grosfeld, J.L., O\u2019Neil, J.A., Fonkalsrud, E.W., and Corab, A.G. (2006). Congenital Chest Wall Deformities, Mosby. [6th ed.]."},{"key":"ref_107","first-page":"259","article-title":"Growth of the ribs at the costochondral junction in the rat","volume":"181","year":"1992","journal-title":"J. Anat."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/j.jpedsurg.2008.09.023","article-title":"Does overgrowth of costal cartilage cause pectus excavatum? A study on the lengths of ribs and costal cartilages in asymmetric patients","volume":"44","author":"Nakaoka","year":"2009","journal-title":"J. Pediatr. Surg."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1016\/j.jpedsurg.2010.04.018","article-title":"Overgrowth of costal cartilage is not the etiology of pec-tus excavatum","volume":"45","author":"Nakaoka","year":"2010","journal-title":"J. Pediatr. Surg."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1159\/000449133","article-title":"Costal Cartilages Do Not Overgrow in Patients with Pectus Excavatum","volume":"25","author":"David","year":"2016","journal-title":"Med. Princ. Pract."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"279","DOI":"10.5606\/tgkdc.dergisi.2018.15009","article-title":"Determination of severity of deformity with rib length to costal cartilage length ratio in thorax deformities","volume":"26","year":"2018","journal-title":"Turk. J. Thorac. Cardiovasc. Surg."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jss.2018.09.080","article-title":"Against the Overgrowth Hypothesis: Shorter Costal Cartilage Lengths in Pectus Excavatum","volume":"235","author":"Eisinger","year":"2019","journal-title":"J. Surg. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/j.jpedsurg.2015.07.010","article-title":"Rib overgrowth may be a contributing factor for pectus excavatum: Evaluation of prepubertal patients younger than 10years old","volume":"50","author":"Park","year":"2015","journal-title":"J. Pediatr. Surg."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s00383-020-04622-2","article-title":"The costochondral length in patients with pectus excavatum is longer than that of the normal thorax","volume":"36","author":"Kondo","year":"2020","journal-title":"Pediatr. Surg. Int."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1007\/s002470050602","article-title":"Growth disturbance of the sternum and pectus deformities: Imaging studies and clinical correlation","volume":"29","author":"Haje","year":"1999","journal-title":"Pediatr Radiol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00383-016-3996-9","article-title":"Measurement of sternal curvature angle on patients with pectus excavatum","volume":"33","author":"Lee","year":"2017","journal-title":"Pediatr Surg Int."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1590\/1413-785220212905243733","article-title":"Analysis of sternal curvature patterns in patients with pectus and control","volume":"29","author":"Haje","year":"2021","journal-title":"Acta Ortop Bras."},{"key":"ref_118","first-page":"6429","article-title":"Establishment of a rabbit model of pectus excavatum","volume":"10","author":"Wang","year":"2017","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"David, V.-L., Ciornei, B., Horhat, F.-G., Amaricai, E., Horhat, I.-D., Hoinoiu, T., and Boia, E.-S. (2020). Rat Animal Model of Pectus Excavatum. Life, 10.","DOI":"10.3390\/life10060096"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"146","DOI":"10.3892\/etm.2021.11069","article-title":"S: Costal cartilage overgrowth does not induce pectus-like deformation in the chest wall of a rat model","volume":"23","author":"David","year":"2022","journal-title":"Exp. Ther. Med."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/5\/1241\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:27:05Z","timestamp":1760135225000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/5\/1241"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,24]]},"references-count":120,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["jcm11051241"],"URL":"https:\/\/doi.org\/10.3390\/jcm11051241","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,24]]}}}