Donald R. Laub Jr. Editor Congenital Anomalies é the Upper sl ACO NL Managementache Aen Heh Ca ere Cess Ho {ety re Segre ek er rc emo pap Ses Me a 25 ‘strstr arr mpl ct ‘tot pe pre el rene Ch a ttheEmbryology and Classification ‘of Congenital Upper Limb Anomalies Carlos Garido-Allepuz Herrera, Michae! Tonkin, ‘and Kerby C. Oberg ‘Morphotogieal Overview Invented bad sts aan scam fle ston tet pie mesoderm (0 ean os “mate wa Thea coe [pecs Ia hus the upper ib bd apes ing ‘ge 2) sisted etc tes and 1256 a) [1S2} Tin cme ny coi ones feb ‘wn asin els The poston in el thug tote pes bya uiane a ula son th of Hox easton fos ee 1s By ay 3 eeopmens Care sage 19) etal peste thin ean te copie cn tne A he ‘Se time thee Is poresine mafema eniesation longterm te seit cement Se nega Ee ater se ope cer ey mea {ent Sn SSW 3 A SSA KC Ones MDP.) ‘ps Pol a i La inde the im By dy 6 te major mel tes of he Ti a com Umb initiation Afr hye in el he Men esi inn of limb es mia ete peters, wie nob elt {PM teint diese sony [5 Tals 0 ie fags oy ht te LPM bjt tefl hb ‘nae te dail FiO expen nes ees ‘hen eke Inchon the expense Te an Wh Indo of Ff th pesngine Fe 2) (6-8 Rec se sega Tbs expen canbe me ‘mpl by How ein acre sgn le for ow sees neh posting i ee ing lemon Ff10treughseepor Fore ‘town nbs Wat a Waa prgecive meses ‘ck in ccm. spetely Cnc. one Mainz Pein Brg sein ni vel e- ‘eo nda nner he pempne ‘etka ge AER) te deme bay TT0c1 ttm, Wa oe Wat es Fg 2 Wah sin pen mn nt prc lof AERIS. "Epoch een famed AER man ‘apres of Fn the mesma pst ‘Sy np th nas rox dtl pest 1) Inde of in bl agpess tbe etn i RA he ‘Sih male an Th a pro ‘hevombesft embry theme Raa 315 RA fetes the ely ees fF within the hear el. ‘hint, eis Be agssone TS intin eh ‘tie ln development [17 Batsmoe, RA hasteet shown eget exes of Ho ees bth SAERASESLAMe Eargasm, univ ich any cobs ind etter Son andor poston Gee i 12311 | A La Come nones of the er Ey: nn Met 2 "espe Sincere ssc aeDip pecfeaton —AnagenFamaton Dg Dereon 3 pt Tp Formston ——S S6G: ‘S ‘niet ht Mea tomig ge Hague A th Fig 18 stapes ring pt ep Ate bn Ss name ane SA pene ai ‘sity ae ne i eosin etl mesa ss DD) ths ey ine AE crag anasto ce weer nde ts hens gro Re mae re «inocu sie The PA cnet wn eA emis ath psio Te erp ae “entre Bg terms den peste Me AE nie ih aes tl rng a Soe elem Spe mei a nS nage on Oe) ToxS IN ToxlMox MM Hoxat3 IM Hoxd13 I Hoxd12 IM Shh IM GUSR 2338 Moles inion turner. The resin hm nai PT dey he vr cee TS ‘ha, Tee Fd mci fee 2) he eases mas preg is 2 ‘tem ton min as Hod ab ree ee epg pee gee os Oe [Sn eyo Oh me Lands Urty oxd0-13 amin fos within he developing its Intrtdcaly GL [0 However, the form of G3 ret atoch dit ani edo he Sirus GSR {is ctor coume grates [1]. nadton, Sides {Bp grin tht ko Kron to gle Sgt ore 5p [6,92 The signal etre dt merpolo are enveye tthe PF hough he afjacen Posteri taste (87.9 and hough Ft and Wat pris seed from the onryng AER [88 9-56). Change in he ne {igh BMP eels or swaping inert mesenchyme cn ‘earsform dg mpg 187,991 "The tha cin ert gin spe, poi in.an strate 97} is Shedependen and ss co pliion of gence expeesed within is domain hat Sx Aisin from ote dis Fg 9). Hwa sexes iti the cate handplae (75. 76) and ops the ‘epson of Th, whch extn ino the ctf od tah ‘Soins at ot nthe domain ofthe wna digit gts 2-803} Moreover. the thumb dri accente bythe Ihe of Skircpuined Houd10-12 expression [99]. The sence of dal House expres has Bee wed at 2 marker ‘of “thumbwess across species [100.101 Interestingly, he wit aoa zone wih ied Hox eo ‘win Hor? expression), Recent experiments with monse Imus that expess Tow els af How proteins showed {eamormatio of mac ones 0 cai mete [100 Ths, ToxS and ow eel of Ho ransrition fc {ors ay init these of he tb deal es, he the dnl Hoxd meri faster ae thous lomete sigs (75,98 103). "The mia planes dlferstsctraly om athera agg: thy are cone shaped ad associated witha suice ‘odie a he dap ale he unui nal, hh iene keane epitm that pet the pote igi Termal planes ao sie in heir evelopment1 krtnelear and Ceol ogee rome 5 re cree as ‘ere Saar stop wire sel clement th ume deve © thence pment gpd wie ea ‘Se ln frm: and 3) he ital segment espe be ‘te cals mera and iis form aero sng he PD ss ending inh na soit te oon oth NER, te ser he fsa deren! body afte developing ib ‘Tye ABE sce rts gon tors Fb) eae rma rouble P-D patria. F the isa ical ms ipo Fe ere om the ‘AER ag induct aed wat AER ‘eerues, when the raft he st panes formed ph Fahad Ff oe tat etal be one ‘AER sad xpd ater spect he in ce ps2] Casal crperinens incickembryensbowed AHN AER el td a ink ogroh deed {tte tht compel to he ing of AER ‘esoa: mote wor heater he AER rer he ne (isa esac nt were preset [2] Maver FO Sle pads mre ew rer in eto Interming afer AER rena inating ha a were he coasting cor te AER 2,29) “Ange Aro Fy expe. Fp sag he ste man AER snl ile Figs Feo eT aro ‘ced econo dnt [0 31} Tis eonce i sp rd tom experinens wth Ff Holcoat mice ‘Shower AFR dele in bp ass ‘tome let lems 28 3 la cota, Kent tice he Fal, Fig9 ane Fl? id ot dev esd ‘Sores Ieee Ffeapesson ie Fg kc nice was eprcpliesgesting that eat exes bs my tae lene te plete! he mt Ts ‘scoot eal of Bth Ft and Fy at Scapula Humerus corpatsPhalanges Metatarpals: Coe Stylopod Zeugopod —Autopod ened in mee pete with ty ale in tas 235 ‘See del hve Bon pope fo PD patering ‘Te pres one mel pos ht mesenchymal ss teint ye ng ate prune het Ineo uf the AER in pole fx cll he owes Zone (PZ) [4 5-Te ey secieaton mode [hepa tn he -D tit sedeyad tbe ist pogenior pols exp openly li owe The dle ot moll age hat he Sto he ib expand els tat oor ade ‘heintence of te AER dle [57 oweer he cml iene pro ers ie mel The to sgl dl [0] perpen tat ‘pyoung sigmlspatrne linha the PD an: RA, Fat fom the AER wl specif sal fae) (38, 59) sr, RL oie Retin frm RA tc ‘at et aly ie eimai hw poate ress of Mes a Mei Te exeston oes {kes the osm nb scent nd where te haere {Snopd) ei evcp. Dist. Ft sigling tnces SH gecs Ha Hvala ae il Mei 2 xpremin Alhogh th mecha fe epson tov rst Hin ha ening se {heexgeson of C720) i te dl esechyne a Te i the pet f i ee nes RA o 3 Fp 140 12 Some ne quested RA role rox Iaizing wet i al rer nein ae wartF Proximal Distal Patterning so S99 soi 016 Sioa q ‘Anterior Posteriv/Radial-Uinar Patterning F i) 5 sy sgt ay Fig 14 Mer puta eine posal at & ari rsh ten Frese cme ein sg he estat ous hen wom idem candy seg a Ou ‘em aren wae Me So re sop Hal ne sh ee oan Hts mas pe hua) Opps or of ee (GL) wl Sma al eng {St eh tes ms en ot ah i i) inn mney RE Ohm sas md ery Anterior Posteror/Radlal-Ulnar Patterning nthe upper limb, the stp forms a small atage (amu) endsston [23 0), whe th owe i, he atop sn of sno dg with wo pang (2.50) ‘Te im slong the ALPR-U ais is divided ino two seg-A-PIR-U polity and ebseqen Shhepresson i mets: th avo ada), compises the thu aad, ted by axa Hox gene sentation 51 lowed y = ‘Sethe ptr lu) with tl onda isso tr ha contrite 1 Sih ndacton andthe {wo though) [1 ‘stishneat of the ZPA Hun, expres in he poser Paterno dcvepmsat along the A-PIR-U as cone a al fhe i ds oie for Sb nd [3 tll ty the one af poling actity CZPA), leer af Sanda been showed nrc wih in spi ‘mesenchymal cell maniined fate dial potenoclar SH seplony region [Ss]. Sime, dal Mond spt ofthe developing lib sce Fig 4. Th ZPA nas (Hoxd1O13) vanscision txts aso intact wih the ‘conredin 968 though atingexperncns nck ib Mespecie Sh regulary tein, and evience suggests fe [2] I ese xperinent pra ram the Stal pote at initial phase of i bad expression help cae sna mescncyme wer exc mane group f chicks Shh expeson (Fi. |) 155. nd then ised it the tl terial spect of The tor iil phan of distal Mond expen in the ‘mote goup of ticks. Tein that develope re thse i bud ous ina ested linea (coresping thir falls dentate mir image dpaon of stucees_ gene oer fashion along the atenoe pst as with [Het]. Rh wafonto ee ist molecule thins Hon exthtng te brow sal exession domain "PA gratis when apd othe distal aetna spect af The expession ofeach teesinely moe dsl Hoe go ‘en ud 451) Lar it was shown tat Sth mu the is mste wii th previous gee’ expresson dol se mle espns forthe psp ince by RA] Fig 1) Hox, the terial tase facto ithe ‘St isc tthe comes developmental pate ofthe Head citer, fat the mont otic eapresion doe limb, particu forthe forearm t2eagopd) and and within the stl poste or ulnar aspect ofthe lin bat (autpe) This demoastaed ia Si knock-out mice, oveapig he ZPA. This seo distal Hox expres Imhich hae conmslydencoped ylood, single skeleton play aroein lain Sthexpesson a temporally slement ads) fr the Zend, nd minimal stood coeds to eis of the forearm o zeusFF cone = Hox Paaoge ) carnegie Stage 12 Embryo 6.12 Me patil nin Dei of Socal ari eh ee “thee. Mitre meer. Caney of KC Chery a etn nay ‘Signaling Centers eencen he fut nd ght wees of developmen te Ig hl ners rch a iereaation no iio fly pated nt Ths pes en be Ses ‘Steer pte ceria (A-PICU sd er Senta (D-¥) moda he sili centers (20), "Nog te P-D aa th ABR appease chee o> dam veyng the dal age of he in fad 21) The [AER te spa ener tht reels he P-D growth ‘Su Fat ar the signaling cer at sco ie Fens Excnon af fe AER schon cient ir ‘sal the esting taneaow (22) polusing atity (PA acter of moderna cls Fated a he dsl poser) sun Th ZPA des teed fanction. Both mice (Sth Kock oat) Eat ck Shinn or maa chicks (Olgas Oad are a of postr aan lens 2). ‘eral on AER std det D-Vpatrning wih Warangal rome doesn formation del src wih the etal asp oe ‘in 25 Patterned Development Along {Coordinate Axes Pater formation es sey which cel teste the toll src the lin os sexton we trl oss th Posen of utermig comp slong ach us red by th sealing cers he “sot okays een hth kt ‘img peter ie nein tne Proximal-Distal Patterning (P-0) “Th per inca edd ino te difeent segrntsInt he eatpery of ale of dfereniation Mia et 10a angel Seager nomen log ‘almechinim auerlf nd yar anc Seihattey set print ne tte ee of ‘nattow of iia ye. Casiingcngeial sence of ‘Syniay. symbachyacly (ypc lt aml and Te Schl say hab spopisa waco = Sterol omaton lng ea ane ye opotone wassup ac ender, The Sect, say showed + mache egeney of ener 2 ol Tre wn le spiny ge Sap ete (Ge cacpries of tmrvene amet and yates ‘mening nected sn ae aman. Oe dire {sls feguncie ae abo isl em the ill Epidemiologic les a mprta eha plt- eg detig sage incest ad ep {ng difeenes among regions Tes mo al popula steno CAUE ceo tl ince fuer Thee [opulatcn stolies ae slighy higher than he eximsid ‘lle2 Id micas of mei moma of be ‘pecan CALE app ase Sy ite sa cmy Seen Sem Gee 8) opine eening for weanent Table 23) 9, 10 17-01 ie fy nvr poet er reament png adesowin to dierent claniSesin states ad ‘Sitnons iin he HSSH slnteon For este ‘onto of CAUE a Eterg UKIZ, UT andwo ste ee apn, sh mek itr ree ‘qeny of idence of duplication: presmably sock a {tng otal aap oem ‘mastication oe Table 2) We ope at the ons (Beowti ofdeseaton pte for AU ane Ca) ‘sil are imprnement in gion td poplin “The gertic of an oration hve aleay been vied (Chop. Tee pene patenge we igily eed rough chick apd ose ass Gent ies ef aa ‘aloration and malerntioe somes ve aoe ‘ter mah Congenital and malonate carb ae ‘Sat cheme ue the rd desigmtoaf py iach. bachyccy and oleic or wdicion Porto ange ptien of mulermtion Aough here se ‘vera hunde ecognze syne with ad amas ‘lle22 lcd peri ey ones inl eon Sy Soe ones oom Tio fees am SS Kodi 5) Geeta 1] Kult 6] Regal li] Amel 7) Feserand a)® “e26 Gberckoal yirme aonctl phy ean OM Sylone te eral ees 7 Cayo eemee Feta iactontsyy mdse rata ALD Sh lchemy mmmnata RAS? Camila Gate pe Pet pera etx sme stnagagtons ——ABIITIO ‘Courvenesagh.2 (ee cpoptyeacyy Prats! Pea pple sy cnn, ADITSND ae een oor a Meme pracy fanaa mt at ADVISSIO eee eee cereal rar Ses as Sipe Gu Rae I Posisncestal Hyams henpehatoma pope pert ANEAS0