Razlika između verzija stranice "Sindrom Cornelije de Lange"

'''Sindrom Cornelije de Lange''' ('''CdLS''') je [[genetički poremećaj]]. Osobe s ovim sindromom doživljavaju niz fizičkih, kognitivnih i medicinskih izazova u rasponu od blagih do teških. Sindrom ima vrlo raznolik [[fenotip]], što znači da pogođeni imaju različite karakteristike i izazove. Tipska obilježja CdLS-a uključuju debele ili dugačke [[obrve]], mali [[nos]], [[nizak rast]], [[zaostajanje u razvoju]], dug ili gladak [[filtrum]], tanku gornju [[usna|usnu]] i spuštena [[usta]].<ref name="Kline et al 2018">{{cite journal |last1=Kline |first1=Antonie D. |last2=Moss |first2=Joanna F. |last3=Selicorni |first3=Angelo |last4=Bisgaard |first4=Anne-Marie |last5=Deardorff |first5=Matthew A. |last6=Gillett |first6=Peter M. |last7=Ishman |first7=Stacey L. |last8=Kerr |first8=Lynne M. |last9=Levin |first9=Alex V. |last10=Mulder |first10=Paul A. |last11=Ramos |first11=Feliciano J. |last12=Wierzba |first12=Jolanta |last13=Ajmone |first13=Paola Francesca |last14=Axtell |first14=David |last15=Blagowidow |first15=Natalie |last16=Cereda |first16=Anna |last17=Costantino |first17=Antonella |last18=Cormier-Daire |first18=Valerie |last19=FitzPatrick |first19=David |last20=Grados |first20=Marco |last21=Groves |first21=Laura |last22=Guthrie |first22=Whitney |last23=Huisman |first23=Sylvia |last24=Kaiser |first24=Frank J. |last25=Koekkoek |first25=Gerritjan |last26=Levis |first26=Mary |last27=Mariani |first27=Milena |last28=McCleery |first28=Joseph P. |last29=Menke |first29=Leonie A. |last30=Metrena |first30=Amy |last31=O’Connor |first31=Julia |last32=Oliver |first32=Chris |last33=Pie |first33=Juan |last34=Piening |first34=Sigrid |last35=Potter |first35=Carol J. |last36=Quaglio |first36=Ana L. |last37=Redeker |first37=Egbert |last38=Richman |first38=David |last39=Rigamonti |first39=Claudia |last40=Shi |first40=Angell |last41=Tümer |first41=Zeynep |last42=Van Balkom |first42=Ingrid D. C. |last43=Hennekam |first43=Raoul C. |title=Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement |journal=Nature Reviews Genetics |date=Octoberoktobar 2018 |volume=19 |issue=10 |pages=649–666 |doi=10.1038/s41576-018-0031-0 |pmid=29995837 |pmc=7136165 }}</ref>

Sindrom je dobio ime po nizozemskoj [[pedijatrija|pedijatrici]] [[Cornelia Catharina de Lange| Corneliji Catharini de Lange]], koja ga je opisala 1933. godine.

* Abnormalnosti vida (npr. [[ptoza]], [[nistagmus| patološki nistagmus]], visoka [[miopija]], [[hipertropija]])

Djeca s ovim sindromom često imaju duge [[trepavice]], guste [[obrve]] i [[sinofris]] (spojene obrve). [[tjelesna dlakavost|Dlake na tijelu]] mogu biti pretjerane, a pogođene osobe su često niže od članova svoje uže porodice. Imaju karakterističan [[fenotip]] [[lice (anatomija)|lica]]].<ref>{{cite journal|doi=10.1111/cge.12716|pmid=26663098|title=Recognition of the Cornelia de Lange syndrome phenotype with facial dysmorphology novel analysis|journal=Clinical Genetics|volume=89|issue=5|pages=557–563|year=2016|last1=Basel-Vanagaite|first1=L.|last2=Wolf|first2=L.|last3=Orin|first3=M.|last4=Larizza|first4=L.|last5=Gervasini|first5=C.|last6=Krantz|first6=I.D.|last7=Deardoff|first7=M.A.|s2cid=45748040}}</ref>

Smatra se da je velika većina slučajeva posljedica spontanih genetičkih [[mutacija]].<ref name="Kline et al 2018"/> Mogu biti povezani i sa mutacijama koje pogađaju [[kohezin]]ski kompleks.<ref name="pmid19793304">{{cite journal |last1=Liu |first1=J |last2=Krantz |first2=ID |title=Cornelia de Lange syndrome, cohesin, and beyond |journal=Clinical Genetics |date=Octoberoktobar 2009 |volume=76 |issue=4 |pages=303–314 |doi=10.1111/j.1399-0004.2009.01271.x |pmid=19793304 |pmc=2853897 }}</ref>

| Gen odgovoran za CdLS na [[hromosom 5|hromosomu 5]] otkriven je 2004. Godine, što su zajedno uradili istraživači u Children's Hospital of Philadelphia, [[SAD]] <ref>{{cite journal |last1=Krantz |first1=Ian D |last2=McCallum |first2=Jennifer |last3=DeScipio |first3=Cheryl |last4=Kaur |first4=Maninder |last5=Gillis |first5=Lynette A |last6=Yaeger |first6=Dinah |last7=Jukofsky |first7=Lori |last8=Wasserman |first8=Nora |last9=Bottani |first9=Armand |last10=Morris |first10=Colleen A |last11=Nowaczyk |first11=Malgorzata J M |last12=Toriello |first12=Helga |last13=Bamshad |first13=Michael J |last14=Carey |first14=John C |last15=Rappaport |first15=Eric |last16=Kawauchi |first16=Shimako |last17=Lander |first17=Arthur D |last18=Calof |first18=Anne L |last19=Li |first19=Hui-hua |last20=Devoto |first20=Marcella |last21=Jackson |first21=Laird G |title=Cornelia de Lange syndrome is caused by mutations in NIPBL, the human homolog of Drosophila melanogaster Nipped-B |journal=Nature Genetics |date=Junejuni 2004 |volume=36 |issue=6 |pages=631–635 |doi=10.1038/ng1364 |pmid=15146186 |pmc=4902017 }}</ref> i na Newcastle University, [[Ujedinjeno Kraljevstvo|UK]].<ref>{{cite journal |vauthors=Tonkin E, Wang TJ, Lisgo S, Bamshad MJ, Strachan T |title=NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome |journal=Nature Genetics |volume=36 |issue=6 |pages=636–641 |year=2004 |pmid=15146185 |doi=10.1038/ng1363 |doi-access=free }}</ref>

| Italijanski naučnici su 2006. godine pronašli drugi gen na [[hromosom X| hromosomu X]].

U 2004., istraživači iz Dječije bolnice u Filadelfiji ([[SAD|Sjedinjene Američke Države]]) i Univerziteta Newcastle upon Tyne ([[Engleska]]) identificirali su gen (NIPBL) na hromosomu 5 koji uzrokuje CdLS kada je mutiran. Od tada su pronađeni dodatni geni (SMC1A, SMC3 i HDAC8, RAD21) koji uzrokuju CdLS kada se promijene. U julu 2012. godine najavljen je četvrti "CdLS gen" — HDAC8. HDAC8 je X-vezani gen, što znači da se nalazi na [[hromosom X|hromosomu X]]. Osobe sa CdLS koji imaju promjenu gena u HDAC8 čine samo mali dio svih pogođenih CdLS-om.<ref name="CdLS Foundation - HDAC8 FAQ Sheet">{{cite web|title=HDAC8 FAQ Sheet|url=http://www.cdlsusa.org/docs/HDAC8-FAQ-Sheet.pdf|work=CdLS Foundation Web site|publisher=Cornelia de Lange Syndrome Foundation|access-date=12. February2. 2013|archive-url=https://web.archive.org/web/20130903173032/http://www.cdlsusa.org/docs/HDAC8-FAQ-Sheet.pdf|archive-date=3. September9. 2013|url-status=dead}}</ref> Dokazi o vezanosti za hromosomsku poziciju 3q26.3 su mješovi.<ref name="pmid11391654">{{cite journal |last1=Krantz |first1=Ian D. |last2=Tonkin |first2=Emma |last3=Smith |first3=Melanie |last4=Devoto |first4=Marcella |last5=Bottani |first5=Armand |last6=Simpson |first6=Claire |last7=Hofreiter |first7=Mary |last8=Abraham |first8=Vinod |last9=Jukofsky |first9=Lori |last10=Conti |first10=Brian P. |last11=Strachan |first11=Tom |last12=Jackson |first12=Laird |title=Exclusion of linkage to the CDL1 gene region on chromosome 3q26.3 in some familial cases of Cornelia de Lange syndrome |journal=American Journal of Medical Genetics |date=2001 |volume=101 |issue=2 |pages=120–129 |doi=10.1002/1096-8628(20010615)101:2<120::AID-AJMG1319>3.0.CO;2-G |pmid=11391654 |pmc=4896160 }}</ref>

Genetičke promjene povezane sa CdLS su identificirane u genima ''[[NIPBL]]'', ''[[SMC1A]]'' i ''[[SMC3]]'', kao i nedavno identificiranim genima ''[[RAD21]]'' i ''[[HDAC8]]''.<ref name="pmid25209348">{{cite journal |last1=Boyle |first1=M.I. |last2=Jespersgaard |first2=C. |last3=Brøndum-Nielsen |first3=K. |last4=Bisgaard |first4=A.-M. |last5=Tümer |first5=Z. |title=Cornelia de Lange syndrome |journal=Clinical Genetics |date=Julyjuli 2015 |volume=88 |issue=1 |pages=1–12 |doi=10.1111/cge.12499 |pmid=25209348 |s2cid=37580405 }}</ref> Sve ove genetičke promene koje se javljaju kod pacijenata sa CdLS utiču na proteine koji funkcionišu na [[kohezin]]skom putu.<ref name="pmid25209348"/> SMC1A, SMC3 i RAD21 proteini su strukturne komponente kompleksa kohezinskog prstena. NIPBL uključen je u punjenje kohezinskog prstena na [[hromosom]]ima, a HDAC8 deacilira SMC3, kako bi olakšao njegovu funkciju. Put kohezina uključen je u koheziju [[sestrinska hromatida|sestrinskih hromatida]] tokom [[mitoza|mitoze]], [[popravak DNK|popravka DNK]], [[segregacija hromosoma|segregacije hromosoma]] i regulacije razvojne [[ekspresije gena]]. Defekti u ovim funkcijama teoretizirani su da leže u osnovi nekih obilježja CdLS-a.<ref name="pmid20358602">{{cite journal |last1=Pié |first1=Juan |last2=Gil-Rodríguez |first2=María Concepción |last3=Ciero |first3=Milagros |last4=López-Viñas |first4=Eduardo |last5=Ribate |first5=María Pilar |last6=Arnedo |first6=María |last7=Deardorff |first7=Matthew A. |last8=Puisac |first8=Beatriz |last9=Legarreta |first9=Jesús |last10=de Karam |first10=Juan Carlos |last11=Rubio |first11=Encarnación |last12=Bueno |first12=Inés |last13=Baldellou |first13=Antonio |last14=Calvo |first14=Mª Teresa |last15=Casals |first15=Nuria |last16=Olivares |first16=José Luis |last17=Losada |first17=Ana |last18=Hegardt |first18=Fausto G. |last19=Krantz |first19=Ian D. |last20=Gómez-Puertas |first20=Paulino |last21=Ramos |first21=Feliciano J. |title=Mutations and variants in the cohesion factor genes NIPBL , SMC1A , and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome |journal=American Journal of Medical Genetics Part A |date=Aprilapril 2010 |volume=152A |issue=4 |pages=924–929 |doi=10.1002/ajmg.a.33348 |pmid=20358602 |pmc=2923429 }}</ref> Posebno, defektna popravka DNK može biti u osnovi znakova preranog starenja.<ref name="pmid17640042" />

Često se preporučuje interdisciplinarni pristup za liječenje problema povezanih s CdLS. Tim za podsticanje dobrobiti djeteta često uključuje [[Logopedija|govor]], [[radna terapija|radnu]] i [[fizioterapija|fizioterapiju]], nastavnike, [[ljekar]]e i roditelje.<ref name="CdLS Foundation">{{cite news|title=CdLS Foundation – Treatment Protocols|url=http://www.cdlsusa.org/what-is-cdls/treatment-protocols.htm|access-date=12. February2. 2013|date=12. February2. 2013}}</ref>

Prvi dokumentovani slučaj zabilježio je [[Winfried Robert Clemens Brachmann]] (1888–1969), 1916. njemački ljekar koji je pisao o različitim karakteristikama bolesti kod svog 19-godišnjeg pacijenta,<ref>{{cite journal |id={{NAID|10013330170}} | vauthors = Brachmann W | year = 1916 | title = Ein Fall von symmetrischer Monodaktylie durch Ulnadefekt, mit symmetrischer Flughautbildung in den Ellenbeugen, sowie anderen Abnormitaeten (Zwerghaftigkeit, Halsrippen, Behaarung) |trans-title=A case of symmetrical monodactyly, representing ulnar deficiency, with symmetrical antecubital webbing and other abnormalities, (dwarfism, cervical ribs, hirsutism) | journal = Jahrbuch für Kinderheilkunde und physische Erziehung | volume = 84 | pages = 225–235 |language=de }}</ref> a slijedi ga 1933. [[Cornelia Catharina de Lange]] (1871–1950),<ref>{{cite journal |id={{NAID|10013330169}} | vauthors = de Lange C | year = 1933 | title = Sur un type nouveau de degenerescence (typus Amstelodamensis) |trans-title=On a new type of degeneration (typus Amstelodamensis) |language=fr | journal = Arch. Med. Enfants | volume = 36 | pages = 713–719 }}</ref> [[nizozemska]] pedijatrica po kojoj je bolest dobila ime.<ref>{{Cite web | url=http://www.whonamedit.com/synd.cfm/1080.html |title = Brachmann-de Lange syndrome}}</ref> CdLS bio je poznat i kao Brachmann-de Langein sindrom.<ref name=AtoZ>{{cite book|last1=Aitken|first1=Kenneth J.|title=A-Z of Genetic Factors in Autism: A Handbook for Professionals|date=2009|publisher=Jessica Kingsley|location=London|isbn=9781843109761|pages=172–173|url=https://books.google.com/books?id=fSAQBQAAQBAJ&pg=PA173|access-date=December 10,. 12. 2015}}</ref>

[[Kategorija:Jedarne bolesti]]