{{Short description|Congenital anamoly in tetrapods}} {{About|the congenital abnormality|the genus of echinoderm|List of prehistoric echinoderms}} {{Distinguish|Diplopoda}} '''Diplopodia''' is a congenital anomaly in tetrapods that involves duplication of elements of the foot on the hind limb. It comes from the Greek roots diplo = "double" and pod = "foot". Diplopodia is often found in conjunction with other structural abnormalities<ref name=Jones1978>{{cite journal |vauthors=Jones D, Barnes J, Lloyd-Roberts GC |title=Congenital aplasia and dysplasia of the tibia with intact fibula. Classification and management |journal=J Bone Joint Surg Br |volume=60 |issue=1 |pages=31–9 |date=February 1978 |pmid=627576 |doi=10.1302/0301-620X.60B1.627576 |url=http://www.jbjs.org.uk/cgi/pmidlookup?view=long&pmid=627576 }}{{dead link|date=December 2016 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> and can be lethal.<ref name= Taylor1947>{{cite journal |author1=Taylor, W. |author2=C. Gunns | title=Diplopodia: a lethal form of polydactyly in chickens | journal=Journal of Heredity | volume=38 | issue= 3 | pages=66–76 | year=1947|doi=10.1093/oxfordjournals.jhered.a105693 |pmid=20296125 }}</ref> It is more extreme than polydactyly, the presence of extra digits.<ref name=Karchinov1973>{{cite journal |author=Karchinov K |title=Congenital diplopodia with hypoplasia or aplasia of the tibia. A report of six cases |journal=J Bone Joint Surg Br |volume=55 |issue=3 |pages=604–11 |date=August 1973 |pmid=4729026 |doi=10.1302/0301-620X.55B3.604 |url=http://www.jbjs.org.uk/cgi/pmidlookup?view=long&pmid=4729026 }}{{dead link|date=December 2016 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
==Description== The affected leg usually has one foot that is in an approximately normal position.<ref name=Karchinov1973/> The extra foot is composed of at least some metatarsal or tarsal bones and extra digits, though it is usually not complete.<ref name=Karchinov1973/> The feet can be joined together, so that the limb appears to have one large foot,<ref name=Karchinov1973/> or the extra foot can be joined to the limb separately, usually above the level of the other foot.<ref name= Abbott1959>{{cite journal | author= Abbott, Ursula | title= Further studies on diplopodia II. embryological features | journal= Journal of Genetics | volume= 56 | pages= 179–196 | year= 1959 | doi=10.1007/bf02984744| s2cid= 37450408 }}</ref> Diplopodia affects one or both of the hind limbs.<ref name=Karchinov1973/>
==Causes== Recessive alleles of some genes involved in embryonic limb patterning produce bilateral diplopodia,<ref name= Taylor1947/><ref name= Olympio1983>{{cite journal |author1=Olympio, O. |author2=R. Crawford |author3=H. Classen |name-list-style=amp | title= Genetics of the diplopodia-5 mutation in domestic fowl | journal= Journal of Heredity | volume= 74 | issue= 5 | pages= 341–343 | year= 1983|doi=10.1093/oxfordjournals.jhered.a109806 }}</ref> and diplopodia can be experimentally induced in early embryos.<ref name= Summerbell1977>{{Cite book | first1 = D. | last1 = Summerbell | first2 = C. | last2 = Tickle | author2-link = Cheryll Tickle | editor-last = Ede | editor-first = D. | editor2-last = Hinchliffe | editor2-first = J. | editor3-last = Balls | editor3-first = M. | contribution = Pattern formation along the antero-posterior axis of the chick limb bud | title = Vertebrate Limb and Somite Morphogenesis | year = 1977 | place = New York | publisher = Cambridge University Press}}</ref> Many instances of diplopodia in humans have no apparent cause.<ref name= Jones1978/><ref name= Laurin1964>{{cite journal |author1=Laurin, Carroll |author2=J. Favreau |author3=P. Labelle |name-list-style=amp | title= Bilateral absence of the radius and tibia with bilateral reduplication of the ulna and fibula: a case report | journal = J Bone Joint Surg Am | volume = 46 | pages = 137–42 |date=January 1964 | pmid = 14104303|doi=10.2106/00004623-196446010-00014 }}</ref>
People have been able to produce diplopod limbs by increasing sonic hedgehog (shh) signaling in the limb buds of embryos. The zone of polarizing activity (ZPA) in the proximal posterior mesoderm of a tetrapod limb bud is responsible for maintaining the anterior-posterior axis of the growing limb.<ref name= Saunders1968>{{Cite book | first1 = John | last1 = Saunders | first2 = Mary | last2 = Gasseling | editor-last = Fleischmajer | editor-first = Raul | editor2-last = Billingham | editor2-first = Rupert | contribution = Ectodermal-mesenchymal interactions in the origin of limb symmetry | title = Epithelial-Mesenchymal Interactions | year = 1968 | place = Baltimore | publisher = Williams & Williams}}</ref> The ZPA secretes shh protein, which induces formation of the distal segment of the limb, or autopod, with its posterior side facing the ZPA.<ref name= Riddle1993>{{cite journal | author= Riddle, Robert, Randy Johnson, Ed Laufer, and Cliff Tabin | title= Sonic hedgehog mediates the polarizing activity of the ZPA | journal= Cell | volume= 75 | issue= 7 | pages= 1401–1416 | year= 1993 | doi= 10.1016/0092-8674(93)90626-2 | pmid=8269518| s2cid= 4973500 }}</ref> When ZPA cells,<ref name= Summerbell1977/><ref name= Saunders1968/> non-ZPA cells made to express shh,<ref name= Riddle1993/> or simply shh protein-soaked beads<ref name= López-Martínez1995>{{cite journal |vauthors=López-Martínez A, Chang DT, Chiang C, Porter JA, Ros MA, Simandl BK, Beachy PA, Fallon JF | title = Limb-patterning activity and restricted posterior localization of the amino-terminal product of Sonic hedgehog cleavage | journal = Curr. Biol. | volume = 5 | issue = 7 | pages = 791–6 |date=July 1995 | pmid = 7583126 | doi = 10.1016/S0960-9822(95)00156-4 | doi-access = free | bibcode = 1995CBio....5..791L }}</ref> are implanted in the anterior side of a limb bud, the end of the resulting limb is duplicated, as in diplopodia. The posterior autopod on that limb has the normal orientation, and the extra, anterior autopod has a reversed anterior-posterior axis.<ref name= Summerbell1977/><ref name= Saunders1968/> This is because the original ZPA and the added source of shh signaling each induce the formation of an autopod.<ref name= Saunders1968/>
==Diplopodia in humans== Diplopodia is often found in combination with aplasia or hypoplasia of the tibia.<ref name= Jones1978/><ref name=Karchinov1973/> Sometimes, the tibia is replaced by another fibula<ref name= Jones1978/><ref name= Laurin1964/><ref name=Narang1982>{{cite journal |vauthors=Narang IC, Mysorekar VR, Mathur BP |title=Diplopodia with double fibula and agenesis of tibia. A case report |journal=J Bone Joint Surg Br |volume=64 |issue=2 |pages=206–9 |year=1982 |pmid=7068742 |doi=10.1302/0301-620X.64B2.7068742 |doi-access=free }}</ref> The extra foot is almost always joined to the normal foot,<ref name=Karchinov1973/> though a case was described where a nearly complete extra foot joined to the back of the ankle.<ref name= Brower2003>{{cite journal |author1=Brower, Jason |author2=Sandra Wootton-Gorges |author3=John Costouros |author4=Jennette Boakes |author5=Adam Greenspan |name-list-style=amp | title= Congenital diplopodia | journal= Pediatric Radiology | volume= 33 | issue= 11 | pages= 797–799 | year= 2003 | pmid= 12961041 | doi= 10.1007/s00247-003-1017-3|s2cid=5954872 }}</ref>
==Diplopodia in chickens== People have identified five recessive lethal mutations in chickens that cause bilateral diplopodia.<ref name= Olympio1983/><ref name= Rodriguez1996>{{cite journal |vauthors=Rodriguez C, Kos R, Macias D, Abbott UK, Izpisúa Belmonte JC | title = Shh, HoxD, Bmp-2, and Fgf-4 gene expression during development of the polydactylous talpid2, diplopodia1, and diplopodia4 mutant chick limb buds | journal = Developmental Genetics | volume = 19 | issue = 1 | pages = 26–32 | year = 1996 | pmid = 8792606 | doi = 10.1002/(SICI)1520-6408(1996)19:1<26::AID-DVG3>3.0.CO;2-2 }}</ref> The genes are numbered in the order of their discoveries, with the symbols dp-1, dp-2, dp-3, dp-4, and dp-5.
Chickens normally have an anisodactyl toe arrangement, with one short toe pointing backwards and three long toes pointing forwards. In diplopodia, the feet usually lack the normal hind toe and instead develop two to four extra toes at various positions between the hock joint and the front toes.<ref name= Taylor1947/><ref name= Abbott1959/><ref name= Rodriguez1996/><ref name= Landauer1956/><ref name= Maccabe1975>{{cite journal | author= Maccabe, Jeffrey, Astrida Maccabe, Ursula Abbott, and John McCarrey | title= Limb development in Diplopodia4: a polydactylous mutation in the chicken | journal= Journal of Experimental Zoology | volume= 191 | issue= 3 | pages= 383–393 | year= 1975 | pmid= 1127402 | doi= 10.1002/jez.1401910309| bibcode= 1975JEZ...191..383M }}</ref> The toes are almost always connected to extra tarso-metatarsal bones,<ref name= Taylor1947/><ref name= Abbott1959/><ref name= Olympio1983/> though sometimes the toes do not contain any bone.<ref name= Abbott1959/> Embryos with diplopodia have been found with numbers of digits on one wing ranging from one to seven,<ref name= Abbott1959/><ref name= Maccabe1975/><ref name= Taylor1972>{{cite journal | author = Taylor LW | title = Further studies on diplopodia. V. Diplopodia-3 | journal = Can. J. Genet. Cytol. | volume = 14 | issue = 2 | pages = 417–22 |date=June 1972 | pmid = 4559559 | doi=10.1139/g72-052 }}</ref> while normal embryos have three digits per wing. Diplopod limb buds first differ visibly from normal limb buds by their abnormally thick and long apical ectodermal ridges.<ref name= Maccabe1975/><ref name= Coelho1992>{{cite journal |vauthors=Coelho CN, Upholt WB, Kosher RA | title = Role of the chicken homeobox-containing genes GHox-4.6 and GHox-8 in the specification of positional identities during the development of normal and polydactylous chick limb buds | journal = Development | volume = 115 | issue = 2 | pages = 629–37 |date=June 1992 | doi = 10.1242/dev.115.2.629 | pmid = 1358596 | url = http://dev.biologists.org/cgi/pmidlookup?view=long&pmid=1358596 | url-access = subscription }}</ref><ref name= Maccabe1974>{{cite journal |author1=Maccabe, Jeffrey |author2=Ursula Abbott | title= Polarizing and maintenance activities in two polydactylous mutants of the fowl: diplopodia1 and talpid2 | journal= Journal of Embryology and Experimental Morphology | volume= 31 | pages= 735–746 | year= 1974|issue=3 |pmid=4448948 }}</ref><ref name= Abbott1961>{{cite journal |author1=Abbott, Ursula |author2=M. Kieny | title= Sur la croissance in vitro du tibiotarse et du péroné de l'embryon de poulet "diplopode" | journal= Comptes rendus de l'Académie des Sciences | volume= 252 | pages= 1863–1865 | year= 1961}}</ref> Diplopodia usually delays the embryonic growth of cartilage, bone, and tendon by two days, particularly in the limbs.<ref name= Abbott1959/> Other characteristics frequently seen in diplopodia mutants are shortened wings and legs,<ref name= Olympio1983/><ref name= Taylor1972/> short upper beak,<ref name= Taylor1947/><ref name= Olympio1983/><ref name= Taylor1972/> and smaller embryo size.<ref name= Olympio1983/><ref name= Landauer1956/> Many embryos reach the final embryonic stage but then are unable to hatch,<ref name= Abbott1959/><ref name= Olympio1983/><ref name= Taylor1972/> though, diplopod embryos can occasionally hatch and mature.<ref name= Taylor1947/>
Single diplopodia mutations produce wide ranges of phenotypes sharing these general characteristics and can even affect individual chickens' left and right legs differently.<ref name= Landauer1956>{{cite journal | author= Landauer, Walter | title= A second diplopod mutation of the fowl | journal= Journal of Heredity | volume= 47 | issue= 2 | pages= 57–63 | year= 1956| doi= 10.1093/oxfordjournals.jhered.a106607 }}</ref> The ranges of phenotypes produced by the different mutations also overlap broadly, so diplopodia mutations sometimes need to be distinguished by their phenotype distributions.<ref name= Landauer1956/> Dr. Ursula Abbott has extensively studied the phenotypes and descriptions of the first four diplopodia mutations and has ranked them from least severe to most severe: dp-3, dp-1, dp-4, dp-2.<ref name= Taylor1972/>
'''Diplopodia-1'''
This autosomal mutation gives homozygotes duplicated wing tips and feet in front of the usual structures, as in the experimentally induced diplopodia described above.<ref name= Taylor1947/><ref name= Rodriguez1996/> However, unlike the experimentally manipulated embryos, these embryos show no change in shh expression.<ref name= Rodriguez1996/> The embryos express hoxd-11, hoxd-12, hoxd-13, Bmp-2, and Fgf-4 along the whole edge of each limb bud, even though these genes are normally only expressed at the posterior edge.<ref name= Rodriguez1996/>
'''Diplopodia-2'''
This is an autosomal trait that gives a very extreme diplopod phenotype, with up to eight toes on a foot.<ref name= Landauer1956/> In some embryos, the two outer front toes on each foot are joined together.<ref name= Landauer1956/> The trait is now extinct and was never fully characterized.<ref name= Taylor1972/>
'''Diplopodia-3'''
This is an autosomal trait that may be the least severe of the five.
'''Diplopodia-4'''
This sex-linked mutation is similar to the previous mutations, but causes the embryo to grow thicker wing bones.<ref name= Abbott1961/>
'''Diplopodia-5'''
This is an autosomal mutation that gives embryos webbing between the inner two front toes on each foot, in addition to the usual characteristics of diplopodia.<ref name= Olympio1983/> Almost all of the embryos survive to the end of incubation, but they are unable to clear the fluid from their lungs or absorb the blood from their extraembryonic vessels.<ref name= Olympio1983/> These problems always prevent them from hatching.<ref name= Olympio1983/> Almost all diplopodia-5 embryos have only one or two extra toes on each foot, so this mutation causes the least extreme foot malformation.<ref name= Olympio1983/>
==See also== * Limb development * Congenital abnormality * Dysmelia * Sonic hedgehog * Polydactyly
==References== {{reflist}}
{{Congenital malformations and deformations of musculoskeletal system}}
Category:Congenital disorders of musculoskeletal system Category:Supernumerary body parts