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ALSTRÖMOV SINDROM – PREGLED LITERATURE S PRIKAZOM PRIMERA
ALSTRÖM SYNDROME – LITERATURE REVIEW AND CASE PRESENTATION
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9SULVSHYNXSUHGVWDYOMDPR$OVWU|PRYVLQGURPNLMH]HORUHGNDGHGQDDYWRVRPQRUHFHVLYQDEROH]HQ3RY- ]URþDMRPXWDFLMDYJHQXALMS1NLNRGLUDEHOMDNRYLQRL]NDWHUHVHUD]YLMHSULPDUQDPLJHWDOND]DWRVLQGURP XYUãþDPR PHG FLOLRSDWLMH -H YHþVLVWHPVND EROH]HQ ]D NDWHUR VR ]QDþLOQL ]QDNL NRW VR ]JRGQMD GHEHORVW GLVWUR¿MDRþHVQLKSDOLþLFLQþHSNRYNLYRGLYVOHSRWRVHQ]RULQHYUDOQDQDJOXãQRVWGLODWDWLYQDNDUGLRPLRSD- WLMD]JRGQMDLQ]XOLQVNDRGSRUQRVWLQVODGNRUQDEROH]HQWLSD3ULGUXåHQHVRODKNRWXGLGUXJHEROH]QLåOH]]
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9SULVSHYNXSUHGVWDYOMDPRSULPHUOHWQHGHNOLFHNLVPRMRREUDYQDYDOL]DUDGLGLODWDWLYQHNDUGLRPLRSDWLMH .OLQLþQRVPRSRVWDYLOLVXPQD$OVWU|PRYVLQGURPNLVPRJDSRWUGLOL]RSUHGHOLWYLMRPXWDFLMHYJHQXALMS1.
.OMXþQH EHVHGH $OVWU|PRY VLQGURP VLQGURPVND GHEHORVW GLODWDWLYQD NDUGLRPLRSDWLMD LQ]XOLQVND RGSRUQRVWJHQALMS1
ABSTRACT
$OVWU|PV\QGURPHDYHU\UDUHKHUHGLWDU\DXWRVRPDOUHFHVVLYHGLVHDVHLVSUHVHQWHG,WLVFDXVHGE\DPXWDWLRQ in the ALMS1JHQHHQFRGLQJWKHSURWHLQLQYROYHGLQWKHGHYHORSPHQWRISULPDU\FLOLDDQGKHQFHWKHV\Q- GURPHLVFODVVL¿HGDVDFLOLRSDWK\,WLVDPXOWLV\VWHPLFGLVHDVH7KHNH\IHDWXUHVDUHHDUO\REHVLW\FRQHURG UHWLQDO G\VWURSK\ OHDGLQJ WR MXYHQLOH EOLQGQHVV VHQVRULQHXUDO KHDULQJ ORVV GLODWHG FDUGLRP\RSDWK\ HDUO\
LQVXOLQUHVLVWDQFHDQGW\SHGLDEHWHVPHOOLWXV$GGLWLRQDOIHDWXUHVPD\LQFOXGHHQGRFULQRSDWKLHVDQGUHQDO and liver disease.
7KHFDVHRIDQ\HDUROGJLUOGLDJQRVHGZLWKGLODWHGFDUGLRP\RSDWK\LVSUHVHQWHG7KHVXVSHFWHGFOLQLFDO GLDJQRVLVRI$OVWU|PV\QGURPHZDV¿QDOO\FRQ¿UPHGE\WKHGHWHUPLQDWLRQRIDPXWDWLRQLQWKHALMS1 gene.
.H\ZRUGV$OVWU|PV\QGURPHV\QGURPLFREHVLW\GLODWHGFDUGLRP\RSDWK\LQVXOLQUHVLVWDQFHALMS1JHQH 6ORY3HGLDWU
UVOD
ýH]PHUQD SUHKUDQMHQRVW SR VYHWX GRVHJD UD]VH- åQRVWL SDQGHPLMH 2E GHGQL SUHGLVSR]LFLML LPDMR SRPHPEQR YORJR WXGL YSOLYL RNROMD SUHGYVHP neustrezna prehrana in nezadostno telesno udej- VWYRYDQMH 6 WHJD YLGLND VR UHGNH REOLNH GHEH- losti pravzaprav majhen javnozdravstveni problem.
Po drugi strani pa je razumevanje vzrokov redkih oblik debelosti pomembno tudi z vidika poznavanja molekularnih osnov in mehanizmov uravnavanja WHND LQ KRPHRVWD]H HQHUJLMH NL QDP RPRJRþD GD EROMH UD]XPHPR UD]YRM YHþY]URþQR SRJRMHQH WL RELþDMQH GHEHORVWL LQ QDP SRPDJD SUL VQRYDQMX XþLQNRYLWLKVWUDWHJLM]GUDYOMHQMDGHEHORVWL
$OVWU|PRYVLQGURPVLQGURP$OVWURP6$MHUHGND avtosomno recesivna bolezen s pogostostjo manj NRW/HWDJDMHQDâYHGVNHPSUYLþ RSLVDO&DUO+HQU\$OVWU|P'RGDQHVMHRSLVD- QLKSULEOLåQRSULPHURYEROH]QL(QRJODYQLK meril je zgodnja debelost. Ob debelosti so najpo-
PHPEQHMãD PHULOD ãH L]UD]LWD REþXWOMLYRVW RþL ]D VYHWORERGLVWUR¿MDSDOLþQLFLQþHSQLFNLYRGLYVOH- SRWRLQVHQ]RULQHYUDOQDQDJOXãQRVW3RJRVWHMH LQEROM]JRGDMNRWYVSORãQLSRSXODFLMLVHSULEROQLNLK V6$SRMDYOMDMR]DSOHWLGHEHORVWLNRWVRLQ]XOLQVND RGSRUQRVW VODGNRUQD EROH]HQ WLSD KLSHUWULJOLFH- ULGHPLMD KLSRJRQDGL]HP LQ KLSRWLURLGL]HP í .DUGLRPLRSDWLMD.03WHUEROH]QLOHGYLFSOMXþLQ jeter so neposredni vzroki umrljivosti. Med mlaj- ãLPLEROQLNLMHSRJRVWDSUHGYVHPGLODWDWLYQD.03 PHGWHP NR MH SUL RGUDVOLK EROM SRJRVWD OHGYLþQD RGSRYHG=D6$MH]QDþLOQRGDMHL]UDåDQMH NOLþQLK PHULO þDVRYQR ]HOR YDULDELOQR LQ VH ODKNR ]HORUD]OLNXMHWXGL]QRWUDMLVWHGUXåLQH
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6XP QD 6$ SRVWDYLPR QD RVQRYL NOLQLþQLK PHULO 7DEHOD NL VH UD]OLNXMHMR JOHGH QD VWDURVW LQ VH s starostjo tudi spreminjajo. Glede na starost je za
7DEHOD'LDJQRVWLþQDPHULOD]D$OVWU|PRYVLQGURPSRY]HWRSR 7DEOH'LDJQRVWLFFULWHULDIRU$OVWU|PV\QGURPHDGDSWHGDFFRUGLQJWR
6WDURVW 3RWUGLWHYGLDJQR]H *ODYQDPHULOD 3RPRåQDPHULOD íOHWD • JODYQLPHULOLDOL
• JODYQRPHULORLQ SRPRåQLPHULOL
• mutacija ALMS1DOLGUXåLQVND DQDPQH]D6$
• PRWQMHYLGDQLVWDJPXVIRWRIRELMD
• debelost
• dilatativna kardiomiopatija in/ali NURQLþQRVUþQRSRSXãþDQMH íOHW • JODYQLPHULOLDOL
• JODYQRPHULORLQ SRPRåQDPHULOD
• mutacija ALMS1DOLGUXåLQVND DQDPQH]D6$
• PRWQMHYLGDQLVWDJPXVIRWRIRELMD GLVWURILMDþHSQLF
• debelost in/ali inzulinska odpornost in/
DOL7'
• dilatativna kardiomiopatija in/ali NURQLþQRVUþQRSRSXãþDQMH
• motnje sluha
• disfunkcija jeter
• OHGYLþQDRGSRYHG
• SRVSHãHQDNRVWQDVWDURVW 1DGOHW • JODYQLPHULOLLQ
SRPRåQLPHULOLDOL
• JODYQRPHULORLQ SRPRåQDPHULOD
• mutacija ALMS1DOLGUXåLQVND DQDPQH]D6$
• PRWQMHYLGDQLVWDJPXVIRWRIRELMD GLVWURILMDþHSQLFLQSDOLþQLF
• debelost in/ali inzulinska odpornost in/
DOL7'
• dilatativna kardiomiopatija in/ali NURQLþQRVUþQRSRSXãþDQMH
• nizka rast
• hipogonadizem pri fantih
• neredni menstrualni cikel ali hiperandrogenizem pri dekletih
• motnje sluha
• disfunkcija jeter
• OHGYLþQDRGSRYHG
• SRVSHãHQDNRVWQDVWDURVW
postavitev diagnoze potrebno izpolnjevanje raz- OLþQHJD ãWHYLOD PHULO =D SRVWDYLWHY GLDJQR]H MH pomembna tudi analiza gena ALMS1. Mutacija v JHQXMHQDPUHþRVQRYQRPHULORSULSRVWDYLWYLGLD- JQR]H6$7DEHOD
0RWQMHYLGD
Motnje vida so eno od dveh glavnih meril za posta- YLWHYGLDJQR]HLQVRSULVRWQHSULíEROQLNRY V6$7DEHOD1LVWDJPXVLQL]UD]LWDSUHREþXWOML- vost za svetlobo sta prva simptoma bolezni in se UD]YLMHWD åH Y SUYHP OHWX VWDURVWL ,]JXED IXQNFLMH SDOLþQLFLQþHSQLFSRVWRSQRYRGLYVOHSRWR3RJRVWH VR WXGL NDWDUDNWH RþHVQH OHþH LQ VSUHPHPEH åLOMD PUHåQLFH ýHSUDY SRVODEãHYDQMH YLGD QDSUHGXMH ] UD]OLþQRKLWURVWMRSDYGUXJHPGHVHWOHWMXåLYOMHQMD RVOHSLMRYVLEROQLNL
6SHFL¿þQHJD ]GUDYOMHQMD V NDWHULP EL SUHSUHþLOL L]JXERYLGDQL3RPHPEQDMH]JRGQMDUHKDELOLWDFLMD prizadetih otrok in mladostnikov.
0RWQMHVOXKD
9HþLQDEROQLNRYUD]YLMHSRþDVLQDSUHGXMRþR VHQ]RULQHYUDOQR QDJOXãQRVW9HþLQD UD]YLMH VUHGQMH WHåNR GR L]UD]LWR PRWQMR åH Y SUYHP GHVHWOHWMX åLYOMHQMD þHSUDY VR RSLVDQL WXGL SULPHUL SR]QHJD UD]YRMDYRGUDVOLGREL
'D EL XSRþDVQLOL UD]YRM QDJOXãQRVWL PRUDPR SUH- SUHþHYDWL SRQDYOMDMRþD VH YQHWMD VUHGQMHJD XãHVD 2EHWDYQRMH]GUDYOMHQMHVSROåNRYLPLYVDGNL 'HEHORVW LQ]XOLQVND RGSRUQRVW LQ VODGNRUQD EROH]HQWLSD
'HEHORVW MH HGHQ QDM]JRGQHMãLK LQ QDMSRJRVWHMãLK NOLQLþQLK ]QDNRY 3ULVRWQD MH SUL SUDNWLþQR YVHK bolnikih. Bolniki imajo ob rojstvu normalno telesno WHåRL]UD]LWRþH]PHUQRSULGRELYDQMHWHOHVQHWHåHSD VHSULþQHYGUXJHPOHWXåLYOMHQMD0DãþHYMHVHNRSLþL SUHGYVHPYLVFHUDOQR9]URNþH]PHUQHSUHKUDQMHQR- VWLMHGHOQRþH]PHUHQNDORULþQLYQRVPRWQMHWHND
GHOQRSDSUHPDORWHOHVQHGHMDYQRVWLNLMRRPHMXMHMR tudi motnje vida in sluha. Trenutno raziskujejo tudi YORJREHOMDNRYLQH$/06SULSRVSHãHQHPUD]YRMX PDãþREQLKFHOLFDGLSRJHQH]L=DQLPLYRMHGDVH þH]PHUQDSUHKUDQMHQRVWVVWDURVWMRL]EROMãXMH .OMXEWHPXVHQH]DGUåQRUD]YLMDãHHQDNRPSRQHQWD PHWDEROQHJD VLQGURPD í LQ]XOLQVND RGSRUQRVW V KLSHULQ]XOLQL]PRP 8JRWDYOMDPR MR ODKNR åH SUHG SRMDYRPL]UD]LWHGHEHORVWL.DUíEROQLNRY UD]YLMH VODGNRUQR EROH]HQ WLSD 7XGL LQ]XOLQVND RGSRUQRVWVHYUD]OLþQLKREGREMLKWMRGOHWDSD GRRGUDVOHGREHL]UDåDUD]OLþQR6UHGQMDVWDURVWRE SRVWDYLWYL GLDJQR]H MH OHW 3ULSRURþHQL QDþLQL ]GUDYOMHQMD VR SUHGYVHP PDQMãL NDORULþQL YQRV ]QLåHYDQMH WHOHVQH WHåH LQ ]GUDYOMHQMH ] ]GUDYLOL NL SRYHþXMHMR REþXWOMLYRVW WNLY QD LQ]XOLQ .OMXE WHPXSDMHSRL]þUSDQMXFHOLFEHWD/DQJHUKDQVRYLK RWRþNRYSRJRVWRSRWUHEQR]GUDYOMHQMH]LQ]XOLQRP
=DQLPLYR MH GD VR EROQLNL V 6$ ]DãþLWHQL SUHG UD]YRMHPGLDEHWLþQHVHQ]RUQHQHYURSDWLMH
1L]NDUDVWLQGUXJLHQGRNULQRORãNL]DSOHWL 'ROåLQDQRYRURMHQþNRYV6$MHQRUPDOQD'RSXEHU- WHWHRWURFLV6$UDVWHMRKLWUHMHSRGREQRNRWRWURFL ]RELþDMQRGHEHORVWMRLQVRYHþMLRGYUVWQLNRY2E WHP MH SRVSHãHQD WXGL NRVWQD VWDURVW 9 REGREMX SXEHUWHWH VH KLWURVW UDVWL XSRþDVQL LQ RGUDVOL V 6$
VR Y SRYSUHþMX QLåMH UDVWL NRW QMLKRYL YUVWQLNL 3R QDYHGEDKYOLWHUDWXULQDMELODQLåMDUDVW]ODVWLSRVOH- GLFDSRPDQMNOMLYHJDL]ORþDQMDUDVWQHJDKRUPRQDY VNORSX GLVIXQNFLMH KLSRWDODPXVD LQ PRWHQM Y VLV- temu inzulinu podobnega rastnega faktorja. Obsta- jajo tudi opisi primerov zdravljenja nizke rasti pri RVHEDKV6$]UDVWQLPKRUPRQRPí
3UL 6$ ODKNR XJRWDYOMDPR WXGL KLSRWLURLGL]HP KLSRJRQDGL]HP SUHGYVHP SUL PRãNLK FLVWH QD MDMþQLNLKLQKLU]XWL]HPSULåHQVNDK9OLWHUDWXULQL RSLVRYSRVDPH]QLNRYNLELLPHOLRWURNH
.DUGLRPLRSDWLMD
'LODWDWLYQD.03MHSULVRWQDSULíEROQLNRY V6$NLVRRSLVDQLYOLWHUDWXUL3RMDYLVHODKNRSUL NDWHUL NROL VWDURVWL QDMSRJRVWHMH Y YHþ NRW Y SUYLK PHVHFLK åLYOMHQMD LQIDQWLOQD REOLND 3UL PQRJLKRWURFLKVWRREOLNR.03VHVUþQDIXQNFLMD do 3. leta starosti popravi in ostane stabilna tudi YHþ OHW 1HQDGQR SRVODEãDQMH GLODWDWLYQH .03 VH SRMDYL RELþDMQR Y DGROHVFHQFL DOL Y ]JRGQMHP RGUDVOHP REGREMX 1DSUHGRYDOR VUþQR SRSXãþDQMH ]DUDGLNDUGLRPLRSDWLMHMHQDMSRJRVWHMãLY]URNVPUWL SULEROQLNLKV6$HGLQDWHUDSHYWVNDPRåQRVWSDMH SUHVDGLWHYVUFD=DSUHVDGLWHYVHRGORþLPRSULYVHK EROQLNLKNLQLPDMRQDSUHGRYDOHOHGYLþQHDOLMHWUQH LQVX¿FLHQFHLQVRSRSUHVDGLWYLVSRVREQLVDPLVNU- EHWL]D]GUDYOMHQMH
3VLKRPRWRUQLUD]YRM
9HþLQDRVHEV6$MHQRUPDOQRLQWHOLJHQWQLK7HåDYH ]YLGRPLQVOXKRPNLQDVWRSLMRåHSULGRMHQþNLKLQ QHNDMOHWQLK RWURFLK YHUMHWQR YSOLYDMR QD SRJRVWR EODJR XSRþDVQMHQ UD]YRM JURELK LQ ¿QLK PRWRULþ- QLK VSUHWQRVWL 2SLVDQH VR WXGL PRWQMH UDYQRWHåMD in koordinacije ter strukturne nepravilnosti malih PRåJDQRY
'XãHYQHEROH]QLSULEROQLNLKV6$QLVRSRJRVWHMãHNRW YVSORãQLSRSXODFLMLRSLVXMHMRSDSRVDPH]QHSULPHUH WHåMLKGXãHYQLKEROH]QLNRWVRWHåMDREOLNDGHSUHVLMH REVHVLYQRNRPSXO]LYQRYHGHQMHLQSVLKR]H 'UXJHPRWQMH
2VHEHV6$LPDMR]QDþLOQHREUD]QHSRWH]HNRWVR RNURJHO REUD] JORERNR SRORåHQH RþL ]DGHEHOMHQL XKOML UD]EDUYDQL ]REMH QRWUDQMD IURQWDOQD KLSHUR- VWR]D LQ SUH]JRGQMD IURQWDOQD SOHãDYRVW 3UVWL QD URNDK LQ QRJDK VR NUDWNL LQ þRNDWL QL SD RSLVDQLK SULPHURYSROLDOLVLQGDNWLOLMH6WRSDODVRãLURND9 ]JRGQMLKQDMVWQLãNLKOHWLKVHSRJRVWRSRMDYLWDWRUD- NDOQDLQDOLOXPEDOQDVNROLR]DLQDOLNLIR]D 3ULRVHEDKV6$RSLVXMHMRUD]OLþQHPRWQMHYGHORYD- QMXMHWHURGEODJRSRYLãDQLKYUHGQRVWLWUDQVDPLQD]
do steatoze ali celo ciroze jeter s portalno hiperten- ]LMR(GHQPRåQLKY]URNRYMHGHEHORVW /HGYLþQDLQVX¿FLHQFDVHSRMDYLSULEROQLNRY V 6$ 3RþDVL QDSUHGXMRþD QHIURSDWLMD QDSUHGXMRþD JORPHUXOR¿EUR]DLQSRVWRSQDGHVWUXNFLMDOHGYLFVR SUHGYVHP]QDþLOQRVWL6$SULRGUDVOLK+LVWRSDWROR- ãNHVSUHPHPEHYNOMXþXMHMRKLDOLQL]DFLMRWXEXORYLQ LQWHUVWLFLMVNR¿EUR]R
3ULíRVHEV6$VRSULVRWQLWXGL]DSOHWLQD SRGURþMX GLKDO NRW VR NURQLþQL EURQKLWLV DVWPD VLQX]LWLV DOYHROQD KLSRYHQWLODFLMD LQ SRQDYOMDMRþH VHSOMXþQLFH
GEN ALMS1 IN CILIOPATIJE
Gen ALMS1VHQDKDMDQDNUDWNLURþLFLGUXJHJDNUR- PRVRPDSLQYVHEXMHHNVRQRY,]UDåHQMHY ãWHYLOQLKWNLYLKIRWRUHFHSWRUMLK.RUWLMHYHPRUJDQX OHGYLþQLK WXEXOLK MHWULK RWRþNLK WUHEXãQH VOLQDYNH LQKLSRWDODPXVX9UD]OLþQLKWNLYLKMHSUHSLVJHQDY P51$UD]OLþHQ5D]OLþQHL]RIRUPHSURWHLQDLPDMR QDMYHUMHWQHMHWXGLUD]OLþQHIXQNFLMH
9HþLQDYDULDFLMJHQDVHQDKDMDYLQQDMSRJR- VWHMHYHNVRQX1HNDMPXWDFLMMHãHSRVH- bej pogostih. Pri bolnikih niso opredelili mutacij v HNVRQLKíNDUMHYHUMHWQRSRVOHGLFDGHMVWYDGDVR PXWDFLMHYWHPSUHGHOX]D]DURGHNVPUWQH
$6VHGHGXMHDYWRVRPQRUHFHVLYQR3UHQDãDOFL$6 (heterozigoti za mutacijo v genu ALMS1 QLPDMR VLPSWRPRYEROH]QL*HQYVHEXMHãWHYLOQHSROLPRU-
¿]PH NL VR JOHGH QD SRORåDM Y JHQX UD]SRUHMHQL SRGREQR NRW PXWDFLMH 3ROLPRU¿]HP UV MH ãLENRSRYH]DQ]QDJQMHQRVWMR]DPRWQMHYSUHVQRYL NUYQHJDVODGNRUMD
$6XYUãþDPRYVNXSLQRFLOLRSDWLMNLMLKSRY]URþDMR motnje v funkciji primarne migetalke. Primarna PLJHWDONDMHRUJDQHOSULVRWHQYVNRUDMYVHKFHOLFDK sesalcev. Pomembno vlogo igra pri mehanskem in kemijskem zaznavanju ter tudi pri razvoju in delo- YDQMXFHOLFLQWNLYYNDWHULKMHL]UDåHQ
%HOMDNRYLQD$/06MHXPHãþHQDYVWUXNWXULFHQWUR- VRPXL]NDWHUHVHUD]YLMHSULPDUQDPLJHWDOND0RWQMH YL]UDåDQMXLQGHORYDQMXEHOMDNRYLQH$/06VHRGUD-
åDMR Y PRWQMDK GHORYDQMD ãWHYLOQLK WNLY NDU NDåH QD SRPHPEQRYORJRWHEHOMDNRYLQHYUD]OLþQLKWNLYLK
DIFERENCIALNO DIAGNOSTICIRANJE 6$MHQDMEROMSRGREHQEROH]QLPSULNDWHULKVHSRMD- YOMDWD GHEHORVW WHU GLVWUR¿MD SDOLþQLF LQ þHSQLF 7R sta Laurence-Moonov in Bardet-Biedlov sindrom.
Od Bardet-Biedlovega sindroma se razlikuje po RGVRWQRVWLSROLR]VLQGDNWLOLMHRG/DXUHQFH0RR- QRYHJDVLQGURPDSRQDJOXãQRVWLLQRGVRWQRVWLVSD- VWLþQHSDUDSDUH]H97DEHOLSULND]XMHPRVNODGQR- VWLLQUD]OLNH6$JOHGHQDGUXJHVLQGURPH
35,.$=35,0(5$'(./,&$=
ALSTRÖMOVIM SINDROMOM
OHWQRGHNOLFRVRQDSRWLOLQDNDUGLRORãNLRGGH- OHN3HGLDWULþQHNOLQLNHY/MXEOMDQLQDåHOMRVWDUãHY
]DUDGLSULGRELWYHGRGDWQHJDNDUGLRORãNHJDPQHQMD 1HNDM PHVHFHY SUHG WHP MH ELOD QDPUHþ ]DUDGL PHVHFHWUDMDMRþLKWHåDYRWHNDQMHYQRJHXWUXMHQRVW LQEROHþLQHYWUHEXKXVSUHMHWDYEROQLãQLFRNMHUVR ugotovili dilatativno KMP in se po stabilizaciji odlo- þLOL]D]GUDYOMHQMHNURQLþQHJDVUþQHJDSRSXãþDQMD 9GUXåLQVNLDQDPQH]LUD]HQDVWPHSULPDWHULQLELOR NURQLþQLKDOLVUþQLKEROH]QL
Deklica je bila rojena po materini drugi in normalno SRWHNDMRþL QRVHþQRVWL NRW GUXJL RWURN Y GUXåLQL GRPDLPDVWDUHMãHJDEUDWDNLMH]GUDY3RURGVHMH SULþHOVSRQWDQRGQLSRSUHGYLGHQHPURNX5RMHQD MHELOD]QRUPDOQLPLWHOHVQLPLPHUDPL37J 3'FP2*FPRFHQDSR$SJDUMHYL3OR- GRYQLFDMHELODPHNRQLMVND=DUDGLQHRQDWDOQH]ODWH- QLFHMHSRWUHERYDODGQLLQWHUPLWHQWQHIRWRWHUDSLMH VLFHUSDMHELOSRSRURGQLSRWHNEUH]SRVHEQRVWL9 REGREMX GRMHQþND MH SUHEROHYDOD SRJRVWH EURQKL- WLVH3ULVWDURVWLPHVHFDVRSRSDGFXQDJODYR SUYLþRSD]LOLKRUL]RQWDOQLQLVWDJPXVWHUXWULSDQMH]
YHNDPL3ULPHVHFLKMHåHELODþH]PHUQRSUHKUD-
7DEHOD3ULPHUMDYDNOLQLþQLK]QDþLOQRVWL6$VSRGREQLPLEROH]QLPL
7DEOH &RPSDULVRQ RI WKH FOLQLFDO FKDUDFWHULVWLFV WR WKRVH RI GLVHDVHV PRVW UHVHPEOLQJ $OVWU|P V\QGURPH
0RWQMD 3RJRVWRVWPRWQMH
$OVWU|PRYVLQGURP %DUGHW%LHGORYVLQGURP VLQGURP0250 VWUXNWXUQD
vidna í í í
senzorna í /
endokrina í í í
SOMXþQD í / /
OHGYLþQD í í /
jetrna /
razvojna í í í
VUþQD í /
SUHVQRYQD
debelost í í
7' í /
UD]YRMQD
skeletna / /
polidaktilija / /
situs inversus / /
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