{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T11:14:19Z","timestamp":1783509259366,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:p>Midline metatarsal ray deficiencies, which occur in approximately half of congenital short limbs with fibular deficiency, provide the most distal and compelling manifestation of a fluid spectrum of human lower-extremity congenital long bone reductions; this spectrum syndromically affects the long bone triad of the proximal femur, fibula, and midline metatarsals. The bony deficiencies correspond to sites of rapid embryonic arterial transitioning. Long bones first begin to ossify because of vascular invasions of their respective mesenchymal\/cartilage anlagen, proceeding in a proximal-to-distal sequence along the forming embryonic limb. A single-axis artery forms initially in the embryonic lower limb by means of vasculogenesis. Additional arteries evolve in overlapping transitional waves, in proximity to the various anlagen, during the sixth and seventh weeks after fertilization. An adult pattern of vessels presents by the eighth week. Arterial alterations, in the form of retained primitive embryonic vessels and\/or reduced absent adult vessels, have been observed clinically at the aforementioned locations where skeletal reductions occur. Persistence of primitive vessels in association with the triad of long bone reductions allows a heuristic estimation of the time, place, and nature of such coupled vascular and bony dysgeneses. Arterial dysgenesis is postulated to have occurred when the developing arterial and skeletal structures were concurrently vulnerable to teratogenic insults because of embryonic arterial instability, a risk factor during arterial transition. It is herein hypothesized that flawed arterial transitions subject the prefigured long bone cartilage models of the rapidly growing limb to the risk of teratogenesis at one or more of the then most rapidly growing sites. Midline metatarsal deficiency forms the keystone of this developmental concept of an error of limb development, which occurs as a consequence of failed completion of the medial portion of the plantar arch. Therefore, the historical nomenclature of congenital long bone deficiencies will benefit from modification from a current reliance on empirical physical taxonomies to a developmental foundation.<\/jats:p>","DOI":"10.7547\/18-031","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T21:00:36Z","timestamp":1596142836000},"source":"Crossref","is-referenced-by-count":3,"title":["Missing Midline Metatarsals Conform to Plantar Arterial Arch Dysgenesis"],"prefix":"10.3390","volume":"110","author":[{"given":"David R.","family":"Hootnick","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","reference":[{"key":"i8750-7315-110-3-Article_17-b01","series-title":"J Pediatr Orthop","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1097\/BPO.0000000000000646","article-title":"The nature of foot ray deficiency in congenital fibular deficiency","volume":"37","author":"Reyes","year":"2017","unstructured":"Reyes\n              BA\n            \n            \n              Birch\n              JG\n            \n            \n              Hootnick\n              DR\n            \n            :\n\t\t\t\t\t\n          The nature of foot ray deficiency in congenital fibular deficiency.\n\t\t\t\t\tJ Pediatr Orthop37: 332,\n\t\t\t\t\t2017.\n\t\t\t\t2635631310.1097\/BPO.0000000000000646"},{"key":"i8750-7315-110-3-Article_17-b02","series-title":"Birth Def Res","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1002\/bdr2.1349","article-title":"The syndrome of proximal femur, fibula and midline metatarsal long bone deficiencies","volume":"110","author":"Hootnick","year":"2018","unstructured":"Hootnick\n              DR\n            \n            \n              Vargesson\n              N:\n            \n          \n          The syndrome of proximal femur, fibula and midline metatarsal long bone deficiencies.\n\t\t\t\t\tBirth Def Res110: 1188,\n\t\t\t\t\t2018.\n\t\t\t\t10.1002\/bdr2.1349"},{"key":"i8750-7315-110-3-Article_17-b03","series-title":"Radiographics","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1148\/rg.2015140196","article-title":"Common patterns of congenital lower extremity shortening: diagnosis, classification, and follow-up","volume":"35","author":"Bedoya","year":"2015","unstructured":"Bedoya\n              MA\n            \n            \n              Chauvin\n              NA\n            \n            \n              Jaramillo\n              D\n            \n            :\n\t\t\t\t\t\n          Common patterns of congenital lower extremity shortening: diagnosis, classification, and follow-up.\n\t\t\t\t\tRadiographics35: 1191,\n\t\t\t\t\t2015.\n\t\t\t\t10.1148\/rg.201514019626172360"},{"key":"i8750-7315-110-3-Article_17-b04","series-title":"Arch Surg","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1001\/archsurg.1936.01190030002001","article-title":"Congenital defects of femur, fibula and tibia","volume":"33","author":"Freund","year":"1936","unstructured":"Freund\n              E:\n            \n          \n          Congenital defects of femur, fibula and tibia.\n\t\t\t\t\tArch Surg33: 349,\n\t\t\t\t\t1936.\n\t\t\t\t10.1001\/archsurg.1936.01190030002001"},{"key":"i8750-7315-110-3-Article_17-b05","series-title":"Am J Anat","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1002\/aja.1000890202","article-title":"Morphological patterns in limb deficiencies and duplications","volume":"89","author":"O'Rahilly","year":"1951","unstructured":"O'Rahilly\n              R:\n            \n          \n          Morphological patterns in limb deficiencies and duplications.\n\t\t\t\t\tAm J Anat.\n\t\t\t\t\t89: 135,\n\t\t\t\t\t1951.\n\t\t\t\t10.1002\/aja.100089020214894439"},{"key":"i8750-7315-110-3-Article_17-b06","series-title":"J Bone Joint Surg Br","first-page":"133","article-title":"Congenital deficiency of the fibula","volume":"61","author":"Achterman","year":"1979","unstructured":"Achterman\n              C\n            \n            \n              Kalamchi\n              A:\n            \n          \n          Congenital deficiency of the fibula.\n\t\t\t\t\tJ Bone Joint Surg Br.\n\t\t\t\t\t61: 133,\n\t\t\t\t\t1979.\n\t\t\t\t438260"},{"key":"i8750-7315-110-3-Article_17-b07","series-title":"J Bone Joint Surg Am","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.2106\/JBJS.J.00683","article-title":"Congenital fibular deficiency: a review of thirty years' experience at one institution and a proposed classification system based on clinical deformity","volume":"93","author":"Birch","year":"2011","unstructured":"Birch\n              JG\n            \n            \n              Lincoln\n              TL\n            \n            \n              Mack\n              PW\n            \n            :\n\t\t\t\t\t\n          Congenital fibular deficiency: a review of thirty years' experience at one institution and a proposed classification system based on clinical deformity.\n\t\t\t\t\tJ Bone Joint Surg Am.\n\t\t\t\t\t93: 1144,\n\t\t\t\t\t2011.\n\t\t\t\t10.2106\/JBJS.J.00683"},{"key":"i8750-7315-110-3-Article_17-b08","series-title":"J Pediatr Orthop B","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1097\/BPB.0b013e32832d5d7d","article-title":"Limb length discrepancy and congenital limb anomalies in fibular hemimelia","volume":"19","author":"Rodriguez-Ramirez","year":"2010","unstructured":"Rodriguez-Ramirez\n              A\n            \n            \n              Thacker\n              MM\n            \n            \n              Becerra\n              LC\n            \n            :\n\t\t\t\t\t\n          Limb length discrepancy and congenital limb anomalies in fibular hemimelia.\n\t\t\t\t\tJ Pediatr Orthop B19: 436,\n\t\t\t\t\t2010.\n\t\t\t\t10.1097\/BPB.0b013e32832d5d7d20498623"},{"key":"i8750-7315-110-3-Article_17-b09","series-title":"Clin Orthop Relat Res","first-page":"203","article-title":"Jr: Midline metatarsal dysplasia associated with absent fibula","volume":"150","author":"Hootnick","year":"1980","unstructured":"Hootnick\n              DR\n            \n            \n              Levinsohn\n              EM\n            \n            \n              Packard\n              DS\n            \n          \n          Jr: Midline metatarsal dysplasia associated with absent fibula.\n\t\t\t\t\tClin Orthop Relat Res150: 203,\n\t\t\t\t\t1980."},{"key":"i8750-7315-110-3-Article_17-b10","series-title":"Int Orthop","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s00264-006-0293-6","article-title":"Terminal hemimelia of the lower extremity: absent lateral ray and a normal fibula","volume":"32","author":"Baek","year":"2008","unstructured":"Baek\n              GH\n            \n            \n              Kim\n              JK\n            \n            \n              Chung\n              MS\n            \n            :\n\t\t\t\t\t\n          Terminal hemimelia of the lower extremity: absent lateral ray and a normal fibula.\n\t\t\t\t\tInt Orthop32: 263,\n\t\t\t\t\t2008.\n\t\t\t\t10.1007\/s00264-006-0293-6"},{"key":"i8750-7315-110-3-Article_17-b11","series-title":"J Pediatr Orthop B","first-page":"184","article-title":"Findings of fibular hemimelia syndrome with radiographically normal fibulae","volume":"13","author":"Searle","year":"2004","unstructured":"Searle\n              CP\n            \n            \n              Hildebrand\n              RK\n            \n            \n              Lester\n              EL\n            \n            :\n\t\t\t\t\t\n          Findings of fibular hemimelia syndrome with radiographically normal fibulae.\n\t\t\t\t\tJ Pediatr Orthop B13: 184,\n\t\t\t\t\t2004.\n\t\t\t\t15083119"},{"key":"i8750-7315-110-3-Article_17-b12","series-title":"Teratology","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/tera.1420290202","article-title":"The anatomy of a congenitally short limb with clubfoot and ectrodactyly","volume":"29","author":"Hootnick","year":"1984","unstructured":"Hootnick\n              D\n            \n            \n              Packard\n              DS\n              Jr,\n            \n            \n              Levinsohn\n              E\n            \n            :\n\t\t\t\t\t\n          The anatomy of a congenitally short limb with clubfoot and ectrodactyly.\n\t\t\t\t\tTeratology29: 155,\n\t\t\t\t\t1984.\n\t\t\t\t674050210.1002\/tera.1420290202"},{"key":"i8750-7315-110-3-Article_17-b13","series-title":"Skeletal Radiol","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s00256-012-1469-3","article-title":"Intermediate ray deficiency\u2014a new type of lower limb hypoplasia","volume":"42","author":"Koczewski","year":"2013","unstructured":"Koczewski\n              P\n            \n            \n              Shadi\n              M\n            \n            \n              Kotwicki\n              T\n            \n            :\n\t\t\t\t\t\n          Intermediate ray deficiency\u2014a new type of lower limb hypoplasia.\n\t\t\t\t\tSkeletal Radiol42: 377,\n\t\t\t\t\t2013.\n\t\t\t\t10.1007\/s00256-012-1469-322743795"},{"key":"i8750-7315-110-3-Article_17-b14","series-title":"J Bone Joint Surg Am","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.2106\/00004623-198062070-00009","article-title":"Vascular dysgenesis associated with skeletal dysplasia of the lower limb","volume":"62","author":"Hootnick","year":"1980","unstructured":"Hootnick\n              DR\n            \n            \n              Levinsohn\n              EM\n            \n            \n              Randall\n              PA\n            \n            :\n\t\t\t\t\t\n          Vascular dysgenesis associated with skeletal dysplasia of the lower limb.\n\t\t\t\t\tJ Bone Joint Surg Am62: 1123,\n\t\t\t\t\t1980.\n\t\t\t\t743019810.2106\/00004623-198062070-00009"},{"key":"i8750-7315-110-3-Article_17-b15","series-title":"Gray's Anatomy, 13th American Edition","first-page":"658","article-title":"\u201cDevelopment of the Arteries\u201d","author":"Senior","year":"1985","unstructured":"Senior\n              H:\n            \n          \n          \u201cDevelopment of the Arteries\u201d\n          in\n          \n            Gray's Anatomy, 13th American Edition,\n\t\t\t\t\tedited byClemente,CDp658,\n\t\t\t\t\tWilliams & Wilkins,\n\t\t\t\t\tBaltimore, MD,\n\t\t\t\t\t1985."},{"key":"i8750-7315-110-3-Article_17-b16","series-title":"Anat Embryol (Berl)","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF00315559","article-title":"The timing and sequence of events in the development of the limbs in the human embryo","volume":"148","author":"O'Rahilly","year":"1975","unstructured":"O'Rahilly\n              R\n            \n            \n              Gardner\n              E:\n            \n          \n          The timing and sequence of events in the development of the limbs in the human embryo.\n\t\t\t\t\tAnat Embryol (Berl)148: 1,\n\t\t\t\t\t1975.\n\t\t\t\t10.1007\/BF00315559"},{"key":"i8750-7315-110-3-Article_17-b17","series-title":"Human Embryology and Developmental Biology, 5th Ed","author":"Carlson","year":"2014","unstructured":"Carlson\n              BM\n            \n            \n              Kantaputra\n              PN.\n            \n          \n          \n            Human Embryology and Developmental Biology, 5th Ed,\n\t\t\t\t\tElsevier Saunders,\n\t\t\t\t\tPhiladelphia,\n\t\t\t\t\t2014."},{"key":"i8750-7315-110-3-Article_17-b18","series-title":"Development of the Vascular System: Issues in Biomedicine","first-page":"157","article-title":"\u201cTeratological Implications of Soft Tissue Abnormalities Found in Human Lower Limbs with Bony Defects,\u201d","author":"Packard","year":"1991","unstructured":"Packard\n              D\n            \n            \n              Levinsohn\n              EM\n            \n            \n              Hootnick\n              DR:\n            \n          \n          \u201cTeratological Implications of Soft Tissue Abnormalities Found in Human Lower Limbs with Bony Defects,\u201d\n          in\n          \n            Development of the Vascular System: Issues in Biomedicine\n          ,\n\t\t\t\t\tp157,\n\t\t\t\t\tedited byFineberg,RNSherer,GKAuerback,RKarger,\n\t\t\t\t\tBasel, Switzerland,\n\t\t\t\t\t1991."},{"key":"i8750-7315-110-3-Article_17-b19","series-title":"Prog Clin Biol Res","first-page":"417","article-title":"Most human lower limb malformations appear to result from postspecification insults","volume":"383","author":"Packard","year":"1993","unstructured":"Packard\n              DS\n              Jr,\n            \n            \n              Levinsohn\n              EM\n            \n            \n              Hootnick\n              DR:\n            \n          \n          Most human lower limb malformations appear to result from postspecification insults.\n\t\t\t\t\tProg Clin Biol Res383: 417,\n\t\t\t\t\t1993."},{"key":"i8750-7315-110-3-Article_17-b20","series-title":"The Development of the Vascular System","first-page":"149","article-title":"\u201cThe Etiologic Significance of Vascular Pattern Deficiencies in a Human Limb with Diplopodia,\u201d","author":"Hootnick","year":"1991","unstructured":"Hootnick\n              DR\n            \n            \n              Packard\n              DS\n            \n            \n              Levinsohn\n              EM:\n            \n          \n          \u201cThe Etiologic Significance of Vascular Pattern Deficiencies in a Human Limb with Diplopodia,\u201d\n          in\n          \n            The Development of the Vascular System\n          ,\n\t\t\t\t\tp149,\n\t\t\t\t\tedited byFeinberg,RNSherer,GKAuerbach,RKarger,\n\t\t\t\t\tBasel, Switzerland,\n\t\t\t\t\t1991."},{"key":"i8750-7315-110-3-Article_17-b21","series-title":"Teratology","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1002\/tera.1420270205","article-title":"Congenital tibial aplasia with preaxial polydactyly: soft tissue anatomy as a clue to teratogenesis","volume":"27","author":"Hootnick","year":"1983","unstructured":"Hootnick\n              DR\n            \n            \n              Packard\n              DS\n              Jr,\n            \n            \n              Levinsohn\n              EM:\n            \n          \n          Congenital tibial aplasia with preaxial polydactyly: soft tissue anatomy as a clue to teratogenesis.\n\t\t\t\t\tTeratology27: 169,\n\t\t\t\t\t1983.\n\t\t\t\t10.1002\/tera.14202702056867939"},{"key":"i8750-7315-110-3-Article_17-b22","series-title":"Teratology","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1002\/tera.1420360202","article-title":"Soft tissue anomalies in a patient with congenital tibial aplasia and talo-calcaneal synchrondrosis","volume":"36","author":"Hootnick","year":"1987","unstructured":"Hootnick\n              DR\n            \n            \n              Packard\n              DS\n              Jr,\n            \n            \n              Levinsohn\n              EM\n            \n            :\n\t\t\t\t\t\n          Soft tissue anomalies in a patient with congenital tibial aplasia and talo-calcaneal synchrondrosis.\n\t\t\t\t\tTeratology36: 153,\n\t\t\t\t\t1987.\n\t\t\t\t10.1002\/tera.1420360202"},{"key":"i8750-7315-110-3-Article_17-b23","series-title":"Prog Clin Biol Res","first-page":"327","article-title":"Congenital tibial aplasia with polydactyly: implications of arterial anatomy for abnormal limb morphogenesis","volume":"110","author":"Hootnick","year":"1983","unstructured":"Hootnick\n              DR\n            \n            \n              Packard\n              DS\n              Jr,\n            \n            \n              Levinsohn\n              EM:\n            \n          \n          Congenital tibial aplasia with polydactyly: implications of arterial anatomy for abnormal limb morphogenesis.\n\t\t\t\t\tProg Clin Biol Res110: 327,\n\t\t\t\t\t1983.\n\t\t\t\t6828497"},{"key":"i8750-7315-110-3-Article_17-b24","series-title":"Studies of the Development and Decay of the Human Frame","author":"Trueta","year":"1968","unstructured":"Trueta\n              J:\n            \n          \n          \n            Studies of the Development and Decay of the Human Frame\n          ,\n\t\t\t\t\tWB Saunders,\n\t\t\t\t\tPhiladelphia,\n\t\t\t\t\t1968."},{"key":"i8750-7315-110-3-Article_17-b25","series-title":"Dev Cell","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.devcel.2010.07.010","article-title":"Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels","volume":"19","author":"Maes","year":"2010","unstructured":"Maes\n              C\n            \n            \n              Kobayashi\n              T\n            \n            \n              Selig\n              MK\n            \n            :\n\t\t\t\t\t\n          Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels.\n\t\t\t\t\tDev Cell19: 329,\n\t\t\t\t\t2010.\n\t\t\t\t10.1016\/j.devcel.2010.07.010"},{"key":"i8750-7315-110-3-Article_17-b26","series-title":"Calcif Tissue Int","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s00223-012-9689-z","article-title":"Role and regulation of vascularization processes in endochondral bones","volume":"92","author":"Maes","year":"2013","unstructured":"Maes\n              C:\n            \n          \n          Role and regulation of vascularization processes in endochondral bones.\n\t\t\t\t\tCalcif Tissue Int92: 307,\n\t\t\t\t\t2013.\n\t\t\t\t2329213510.1007\/s00223-012-9689-z"},{"key":"i8750-7315-110-3-Article_17-b27","series-title":"Semin Cell Dev Biol","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.semcdb.2016.05.007","article-title":"Signaling pathways effecting crosstalk between cartilage and adjacent tissues: seminars in cell and developmental biology: the biology and pathology of cartilage","volume":"62","author":"Maes","year":"2017","unstructured":"Maes\n              C:\n            \n          \n          Signaling pathways effecting crosstalk between cartilage and adjacent tissues: seminars in cell and developmental biology: the biology and pathology of cartilage.\n\t\t\t\t\tSemin Cell Dev Biol62: 16,\n\t\t\t\t\t2017.\n\t\t\t\t2718095510.1016\/j.semcdb.2016.05.007"},{"key":"i8750-7315-110-3-Article_17-b28","series-title":"Nature","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/nature13145","article-title":"Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone","volume":"507","author":"Kusumbe","year":"2014","unstructured":"Kusumbe\n              AP\n            \n            \n              Ramasamy\n              SK\n            \n            \n              Adams\n              RH:\n            \n          \n          Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone.\n\t\t\t\t\tNature507: 323,\n\t\t\t\t\t2014.\n\t\t\t\t10.1038\/nature1314524646994"},{"key":"i8750-7315-110-3-Article_17-b29","series-title":"Reprod Toxicol","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.reprotox.2016.10.005","article-title":"Arterial dysgenesis and limb defects: clinical and experimental examples","volume":"70","author":"Vargesson","year":"2017","unstructured":"Vargesson\n              N\n            \n            \n              Hootnick\n              DR:\n            \n          \n          Arterial dysgenesis and limb defects: clinical and experimental examples.\n\t\t\t\t\tReprod Toxicol70: 21,\n\t\t\t\t\t2017.\n\t\t\t\t2777374110.1016\/j.reprotox.2016.10.005"},{"key":"i8750-7315-110-3-Article_17-b30","series-title":"Human Embryology, 2nd Ed","author":"Patten","year":"1953","unstructured":"Patten\n              B:\n            \n          \n          \n            Human Embryology, 2nd Ed,\n\t\t\t\t\tMcGraw-Hill,\n\t\t\t\t\tNew York,\n\t\t\t\t\t1953."},{"key":"i8750-7315-110-3-Article_17-b31","series-title":"J Anat","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1046\/j.1469-7580.2003.00133.x","article-title":"Vascularization of the developing chick limb bud: role of the TGF beta signalling pathway","volume":"202","author":"Vargesson","year":"2003","unstructured":"Vargesson\n              N:\n            \n          \n          Vascularization of the developing chick limb bud: role of the TGF beta signalling pathway.\n\t\t\t\t\tJ Anat202: 93,\n\t\t\t\t\t2003.\n\t\t\t\t10.1046\/j.1469-7580.2003.00133.x12587924"},{"key":"i8750-7315-110-3-Article_17-b32","series-title":"Dev Biol","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1006\/dbio.2001.0267","article-title":"Assembly of trunk and limb blood vessels involves extensive migration and vasculogenesis of somite-derived angioblasts","volume":"234","author":"Ambler","year":"2001","unstructured":"Ambler\n              CA\n            \n            \n              Nowicki\n              JL\n            \n            \n              Burke\n              AC\n            \n            :\n\t\t\t\t\t\n          Assembly of trunk and limb blood vessels involves extensive migration and vasculogenesis of somite-derived angioblasts.\n\t\t\t\t\tDev Biol234: 352,\n\t\t\t\t\t2001.\n\t\t\t\t1139700510.1006\/dbio.2001.0267"},{"key":"i8750-7315-110-3-Article_17-b33","series-title":"Am J Anat","first-page":"55","article-title":"The development of the arteries of the human lower extremity","volume":"25","author":"Senior","year":"1919","unstructured":"Senior\n              H:\n            \n          \n          The development of the arteries of the human lower extremity.\n\t\t\t\t\tAm J Anat25: 55,\n\t\t\t\t\t1919."},{"key":"i8750-7315-110-3-Article_17-b34","series-title":"J Anat","first-page":"130","article-title":"An interpretation of the recorded arterial anomalies of the human leg and foot","volume":"53","author":"Senior","year":"1919","unstructured":"Senior\n              HD:\n            \n          \n          An interpretation of the recorded arterial anomalies of the human leg and foot.\n\t\t\t\t\tJ Anat.\n\t\t\t\t\t53: 130,\n\t\t\t\t\t1919.\n\t\t\t\t17103859"},{"key":"i8750-7315-110-3-Article_17-b35","series-title":"Invest Radiol","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1097\/00004424-199104000-00015","article-title":"Jr: Consistent arterial abnormalities associated with a variety of congenital malformations of the human lower limb","volume":"26","author":"Levinsohn","year":"1991","unstructured":"Levinsohn\n              EM\n            \n            \n              Hootnick\n              DR\n            \n            \n              Packard\n              DS\n            \n          \n          Jr: Consistent arterial abnormalities associated with a variety of congenital malformations of the human lower limb.\n\t\t\t\t\tInvest Radiol26: 364,\n\t\t\t\t\t1991.\n\t\t\t\t10.1097\/00004424-199104000-00015"},{"key":"i8750-7315-110-3-Article_17-b36","series-title":"The Clubfoot","article-title":"\u201cA Vascular Hypothesis for the Etiology of Clubfoot,\u201d","author":"Hootnick","year":"1994","unstructured":"Hootnick\n              D\n            \n            \n              Packard\n              DS\n              Jr,\n            \n            \n              Levinsohn\n              E\n            \n            :\n\t\t\t\t\t\n          \u201cA Vascular Hypothesis for the Etiology of Clubfoot,\u201d\n          in\n          \n            The Clubfoot\n          ,\n\t\t\t\t\tedited bySimons,GWSpringer,\n\t\t\t\t\tNew York,\n\t\t\t\t\t1994."},{"key":"i8750-7315-110-3-Article_17-b37","series-title":"Dev Biol","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1006\/dbio.2001.0481","article-title":"Smad7 misexpression during embryonic angiogenesis causes vascular dilation and malformations independently of vascular smooth muscle cell function","volume":"240","author":"Vargesson","year":"2001","unstructured":"Vargesson\n              N\n            \n            \n              Laufer\n              E:\n            \n          \n          Smad7 misexpression during embryonic angiogenesis causes vascular dilation and malformations independently of vascular smooth muscle cell function.\n\t\t\t\t\tDev Biol240: 499,\n\t\t\t\t\t2001.\n\t\t\t\t1178407910.1006\/dbio.2001.0481"},{"key":"i8750-7315-110-3-Article_17-b38","series-title":"Sarrafian's Anatomy of the Foot and Ankle: Descriptive, Topographic, Functional","article-title":"\u201cAngiology,\u201d","author":"Sarrafian","year":"2011","unstructured":"Sarrafian\n              SK\n            \n            \n              Kelikian\n              AS:\n            \n          \n          \u201cAngiology,\u201d\n          in\n          \n            Sarrafian's Anatomy of the Foot and Ankle: Descriptive, Topographic, Functional\n          ,\n\t\t\t\t\tedited byKelikian,ASLippincott Williams & Wilkins,\n\t\t\t\t\tPhiladelphia,\n\t\t\t\t\t2011."},{"key":"i8750-7315-110-3-Article_17-b39","series-title":"J Bone Joint Surg Am","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.2106\/JBJS.H.00902","article-title":"Computed tomographic angiography in proximal femoral focal deficiency","volume":"91","author":"Chomiak","year":"2009","unstructured":"Chomiak\n              J\n            \n            \n              Horak\n              M\n            \n            \n              Masek\n              M\n            \n            :\n\t\t\t\t\t\n          Computed tomographic angiography in proximal femoral focal deficiency.\n\t\t\t\t\tJ Bone Joint Surg Am91: 1954,\n\t\t\t\t\t2009.\n\t\t\t\t1965195510.2106\/JBJS.H.00902"},{"key":"i8750-7315-110-3-Article_17-b40","series-title":"J Bone Joint Surg Br","first-page":"307","article-title":"Congenital short femur. Clinical, genetic and epidemiological comparison of the naturally occurring condition with that caused by thalidomide","volume":"62","author":"Hamanishi","year":"1980","unstructured":"Hamanishi\n              C:\n            \n          \n          Congenital short femur. Clinical, genetic and epidemiological comparison of the naturally occurring condition with that caused by thalidomide.\n\t\t\t\t\tJ Bone Joint Surg Br62: 307,\n\t\t\t\t\t1980.\n\t\t\t\t7410462"},{"key":"i8750-7315-110-3-Article_17-b41","series-title":"J Pediatr Orthop","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1097\/01241398-200207000-00020","article-title":"Association of fibular hemimelia and clubfoot","volume":"22","author":"Caskey","year":"2002","unstructured":"Caskey\n              PM\n            \n            \n              Lester\n              EL:\n            \n          \n          Association of fibular hemimelia and clubfoot.\n\t\t\t\t\tJ Pediatr Orthop22: 522,\n\t\t\t\t\t2002.\n\t\t\t\t10.1097\/01241398-200207000-0002012131452"},{"key":"i8750-7315-110-3-Article_17-b42","series-title":"Am J Anat","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/aja.1000280202","article-title":"Developmental rate and structural expression: an experimental study of twins, \u2018double monsters' and single deformities, and the interaction among embryonic organs during their origin and development","volume":"28","author":"Stockard","year":"1921","unstructured":"Stockard\n              CR:\n            \n          \n          Developmental rate and structural expression: an experimental study of twins, \u2018double monsters' and single deformities, and the interaction among embryonic organs during their origin and development.\n\t\t\t\t\tAm J Anat28: 115,\n\t\t\t\t\t1921.\n\t\t\t\t10.1002\/aja.1000280202"},{"key":"i8750-7315-110-3-Article_17-b43","series-title":"Proc Natl Acad Sci USA","doi-asserted-by":"publisher","first-page":"4082","DOI":"10.1073\/pnas.91.9.4082","article-title":"Thalidomide is an inhibitor of angiogenesis","volume":"91","author":"D'Amato","year":"1994","unstructured":"D'Amato\n              RJ\n            \n            \n              Loughnan\n              MS\n            \n            \n              Flynn\n              E\n            \n            :\n\t\t\t\t\t\n          Thalidomide is an inhibitor of angiogenesis.\n\t\t\t\t\tProc Natl Acad Sci USA91: 4082,\n\t\t\t\t\t1994.\n\t\t\t\t10.1073\/pnas.91.9.40827513432"},{"key":"i8750-7315-110-3-Article_17-b44","series-title":"Proc Natl Acad Sci USA","doi-asserted-by":"publisher","first-page":"8573","DOI":"10.1073\/pnas.0901505106","article-title":"Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation","volume":"106","author":"Therapontos","year":"2009","unstructured":"Therapontos\n              C\n            \n            \n              Erskine\n              L\n            \n            \n              Gardner\n              ER\n            \n            :\n\t\t\t\t\t\n          Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation.\n\t\t\t\t\tProc Natl Acad Sci USA106: 8573,\n\t\t\t\t\t2009.\n\t\t\t\t1943378710.1073\/pnas.0901505106"},{"key":"i8750-7315-110-3-Article_17-b45","series-title":"Birth Defects Res C Embryo Today","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1002\/bdrc.21096","article-title":"Thalidomide-induced teratogenesis: history and mechanisms","volume":"105","author":"Vargesson","year":"2015","unstructured":"Vargesson\n              N:\n            \n          \n          Thalidomide-induced teratogenesis: history and mechanisms.\n\t\t\t\t\tBirth Defects Res C Embryo Today105: 140,\n\t\t\t\t\t2015.\n\t\t\t\t2604393810.1002\/bdrc.21096"},{"key":"i8750-7315-110-3-Article_17-b46","series-title":"ISRN Dev Biol","article-title":"Thalidomide embryopathy: an enigmatic challenge","author":"Vargesson","year":"2013","unstructured":"Vargesson\n              N:\n            \n          \n          Thalidomide embryopathy: an enigmatic challenge.\n\t\t\t\t\tISRN Dev Biol[Q7]2013."},{"key":"i8750-7315-110-3-Article_17-b47","series-title":"Bioessays","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1002\/bies.200900103","article-title":"Thalidomide-induced limb defects: resolving a 50-year-old puzzle","volume":"31","author":"Vargesson","year":"2009","unstructured":"Vargesson\n              N:\n            \n          \n          Thalidomide-induced limb defects: resolving a 50-year-old puzzle.\n\t\t\t\t\tBioessays31: 1327,\n\t\t\t\t\t2009.\n\t\t\t\t1992166010.1002\/bies.200900103"},{"key":"i8750-7315-110-3-Article_17-b48","series-title":"J Anat","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/joa.12060","article-title":"Molecular analysis of regulative events in the developing chick limb","volume":"223","author":"Mahony","year":"2013","unstructured":"Mahony\n              C\n            \n            \n              Vargesson\n              N:\n            \n          \n          Molecular analysis of regulative events in the developing chick limb.\n\t\t\t\t\tJ Anat223: 1,\n\t\t\t\t\t2013.\n\t\t\t\t2367894210.1111\/joa.12060"},{"key":"i8750-7315-110-3-Article_17-b49","series-title":"Oral Surg Oral Med Oral Pathol","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/0030-4220(73)90070-4","article-title":"The pathogenesis of the first and second branchial arch syndrome","volume":"35","author":"Poswillo","year":"1973","unstructured":"Poswillo\n              D:\n            \n          \n          The pathogenesis of the first and second branchial arch syndrome.\n\t\t\t\t\tOral Surg Oral Med Oral Pathol35: 302,\n\t\t\t\t\t1973.\n\t\t\t\t463156810.1016\/0030-4220(73)90070-4"},{"key":"i8750-7315-110-3-Article_17-b50","series-title":"Birth Defects Orig Artic Ser","first-page":"61","article-title":"Hemorrhage in development of the face","volume":"11","author":"Poswillo","year":"1975","unstructured":"Poswillo\n              D:\n            \n          \n          Hemorrhage in development of the face.\n\t\t\t\t\tBirth Defects Orig Artic Ser11: 61,\n\t\t\t\t\t1975.\n\t\t\t\t813794"},{"key":"i8750-7315-110-3-Article_17-b51","series-title":"Biomed Environ Sci","first-page":"15","article-title":"Hematomas and limb skeletal malformations in chicken embryos following exposure to 5-fluoro-2-deoxyuridine","volume":"11","author":"Nolan","year":"1998","unstructured":"Nolan\n              RS\n            \n            \n              Schwartz\n              G\n            \n            \n              Farquharson\n              S\n            \n            :\n\t\t\t\t\t\n          Hematomas and limb skeletal malformations in chicken embryos following exposure to 5-fluoro-2-deoxyuridine.\n\t\t\t\t\tBiomed Environ Sci11: 15,\n\t\t\t\t\t1998.\n\t\t\t\t9559099"},{"key":"i8750-7315-110-3-Article_17-b52","series-title":"Toxicol Lett","first-page":"250","article-title":"Thalidomide leads to mandible hypoplasia through inhibiting angiogenesis and secondary hemorrhage in the fetal craniofacial region in rabbits","volume":"319","author":"Zao","year":"2019","unstructured":"Zao\n              Y\n            \n            \n              Chen\n              Q\n            \n            \n              Chen\n              L\n            \n            :\n\t\t\t\t\t\n          Thalidomide leads to mandible hypoplasia through inhibiting angiogenesis and secondary hemorrhage in the fetal craniofacial region in rabbits.\n\t\t\t\t\tToxicol Lett319: 250,\n\t\t\t\t\t2019.\n\t\t\t\t31778774"},{"key":"i8750-7315-110-3-Article_17-b53","series-title":"Genes Dev","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1101\/gad.1547407","article-title":"Rethinking the proximodistal axis of the vertebrate limb in the molecular era","volume":"21","author":"Tabin","year":"2007","unstructured":"Tabin\n              C\n            \n            \n              Wolpert\n              L:\n            \n          \n          Rethinking the proximodistal axis of the vertebrate limb in the molecular era.\n\t\t\t\t\tGenes Dev21: 1433,\n\t\t\t\t\t2007.\n\t\t\t\t10.1101\/gad.154740717575045"},{"key":"i8750-7315-110-3-Article_17-b54","series-title":"Wiley Interdiscip Rev Dev Biol","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1002\/wdev.59","article-title":"The molecular basis of human congenital limb malformations","volume":"1","author":"Zuniga","year":"2012","unstructured":"Zuniga\n              A\n            \n            \n              Zeller\n              R\n            \n            \n              Probst\n              S:\n            \n          \n          The molecular basis of human congenital limb malformations.\n\t\t\t\t\tWiley Interdiscip Rev Dev Biol.\n\t\t\t\t\t1: 803,\n\t\t\t\t\t2012.\n\t\t\t\t2379962510.1002\/wdev.59"},{"key":"i8750-7315-110-3-Article_17-b55","series-title":"Development","doi-asserted-by":"publisher","first-page":"3810","DOI":"10.1242\/dev.125757","article-title":"Next generation limb development and evolution: old questions, new perspectives","volume":"142","author":"Zuniga","year":"2015","unstructured":"Zuniga\n              A:\n            \n          \n          Next generation limb development and evolution: old questions, new perspectives.\n\t\t\t\t\tDevelopment142: 3810,\n\t\t\t\t\t2015.\n\t\t\t\t2657720410.1242\/dev.125757"}],"container-title":["Journal of the American Podiatric Medical 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