Koolen–De Vriesov sindrom

Koolen–De Vriesov sindrom
(Sindrom mikrodelecije 17q21.31)
Koolen–De Vriesov sindrom; (Sindrom mikrodelecije 17q21.31)
Klasifikacija i vanjski resursi
OMIM	610443
GeneReviews	17q21.31 mikrodelecijski sindrom

Koolen–De Vriesov sindrom (KdVS), znan i kao sindrom mikrodelecije 17q21.31, je rijedak genetički poremećaj izazvan delecijom segmenta hromosoma 17 od šest gena. Ovaj delecijski sindrom otkrile su nezavisno tri različite istraživačke grupe, 2006.^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]

Ispoljavanje uredi

Simptomi povezani sa ovim sindromom su različiti, ali uobičajene karakteristike uključuju: niska porođajna težina, nizak tonus mišića novorođenih, loše hranjenje u dojenačkoj dobi čest potrebno hranjenje u sondi, tokom određenog perioda) i genetički poremećaj zvani oromotorna dispraksija, zajedno sa umjerenim kašnjenjem u razvoju i poteškoće u učenju, ali prijatno ponašanje. Ostale klinički važne karakteristike uključuju epilepsiju, srčane greške defekt pretkomorske komorske pregrade) i bubrežne/urološke anomalije. Srebrenasta depigmentacija pramenova kose zabilježena je kod nekoliko pacijenata. S godinama dolazi do očiglednog ogrubljavanja crta lica.

U 2006., tri nezavisne grupe istovremeno su prijavile mikrodeleciju 17q21.3, pri čemu je svaka grupa prijavila nekoliko pacijenata, a sada je prepoznato kao jedan od najčešćih recidiva sindroma mikrodelecije.^[1]^[2]^[3] U 2007. opisan je pacijent sa malom duplikacijom u istom segmentu DNK.^[10] Na osnovu pregleda kliničkih karakteristika sindroma kod 22 osobe s mikrodelecijom 17q21,31, procjenjuje da je poremećaj prisutan kod 1/16.000 ljudi.^[5]

Genetika uredi

Ponavljajuća delecija iznosi između 500 i 650 kilobaza (Kb) i obuhvata najmanje šest gena, među kojima je protein tau povezan s mikrotubulama (MAPT). Pregledom pet pacijenata, utvrđeno je da roditeljski hromosom iz kojeg potiče delecija nosi uobičajenih 900 kb hromodomskih inverzijskih polimorfizama.^[5] Orijentacija niskih kopija se ponavlja uz bok deletiranog segmenta, što sugerira da inverzija u roditeljskom hromosomu utiče na deleciju u hromosomu djeteta putem mehanizma nealelne homologne rekombinacije (NAHR).

Pogođeni geni uredi

Delecijom koja uzrokuje ovu bolest može se ukloniti do šest različitih gena. Oni uključuju:

Nekarakterizirani protein C17orf69 (poznat i kao FLJ25168).
Protein SPPL2c, navodna intramembranska proteaza, član presenilinskih homologa, SPP/SPPL-proteaza
Receptor hormona koji oslobađa kortikotropin 1 (CRHR1, poznat i kao CRF-R, CRF1)
Tau protein povezan sa mikrotubulama (MAPT)
Neokarakterizirani protein KIAA1267 (poznat i kao DKFZP727C091, KANSL1)

Dijagnoza uredi

Dijagnoza se uspostavlja analizom mikrorezova hromosoma. Simptomi Koolen–de Vreisovog sindroma mogu biti vrlo varijabilni i ne postoji jedan pouzdan klinički znak za uspostavljanje dijagnoze.^[11]

Liječenje uredi

Tretmani se usredsređuju na simptome kod svakog pcijenta i mogu uključivati: ranu fizioterapiju za probleme sa hranjenjem i motorikom, fizioterapiju za jačanje mišića, logopedsku terapiju, znakovni jezik, alternativne ili augmentativne komunikacijske uređaje, specijalno obrazovanje, rutinski antiepilepsijski lijekovi, ortopedska briga za skoliozu, iščašenje kuka i položajne deformacije stopala, liječenje srčanih, bubrežnih, uroloških bolesti i druga medicinska pitanja i operacija za kriptorhizam ako jeprisutan.

Historija uredi

Sindrom je dobio ime po holandskim genetičarima Davidu A. Koolenu i Bertu B. A. de Vriesu, koji su pomogli otkriti sindrom 2006. godine.^[3]

Reference uredi

^ ^a ^b Sharp AJ, Hansen S, Selzer RR, et al. (septembar 2006). "Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome". Nat. Genet. 38 (9): 1038–42. doi:10.1038/ng1862. PMID 16906162.
^ ^a ^b Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L, Gribble S, Curley R, Cumming S, Dunn C, Kalaitzopoulos D, Porter K, Prigmore E, Krepischi-Santos AC, Varela MC, Koiffmann CP, Lees AJ, Rosenberg C, Firth HV, de Silva R, Carter NP (2006). "Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability". Nat Genet. 38 (9): 1032–7. doi:10.1038/ng1858. PMID 16906163.
^ ^a ^b ^c Koolen DA, Vissers LE, Pfundt R, de Leeuw N, Knight SJ, Regan R, Kooy RF, Reyniers E, Romano C, Fichera M, Schinzel A, Baumer A, Anderlid BM, Schoumans J, Knoers NV, van Kessel AG, Sistermans EA, Veltman JA, Brunner HG, De Vries BB (2006). "A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism". Nat Genet. 38 (9): 999–1001. doi:10.1038/ng1853. PMID 16906164.
^ Lupski JR (2006). "Genome structural variation and sporadic disease traits". Nat Genet. 38 (9): 974–6. doi:10.1038/ng0906-974. PMID 16941003.
^ ^a ^b ^c Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ, Goldenberg A, Saugier-Veber P, Pfundt R, Vissers LE, Destrée A, Grisart B, Rooms L, Van der Aa N, Field M, Hackett A, Bell K, Nowaczyk MJ, Mancini GM, Poddighe PJ, Schwartz CE, Rossi E, De Gregori M, Antonacci-Fulton LL, McLellan MD, Garrett JM, Wiechert MA, Miner TL, Crosby S, Ciccone R, Willatt L, Rauch A, Zenker M, Aradhya S, Manning MA, Strom TM, Wagenstaller J, Krepischi-Santos AC, Vianna-Morgante AM, Rosenberg C, Price SM, Stewart H, Shaw-Smith C, Brunner HG, Wilkie AO, Veltman JA, Zuffardi O, Eichler EE, De Vries BB (2008). "Clinical and molecular delineation of the 17q21.31 microdeletion syndrome". J Med Genet. 45 (11): 710–20. doi:10.1136/jmg.2008.058701. PMC 3071570. PMID 18628315.
^ Tan TY, Aftimos S, Worgan L, Susman R, Wilson M, Ghedia S, Kirk EP, Love D, Ronan A, Darmanian A, Slavotinek A, Hogue J, Moeschler JB, Ozmore J, Widmer R, Bruno D, Savarirayan R, Peters G (2009). "Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome". J Med Genet. 46 (7): 480–9. doi:10.1136/jmg.2008.065391. PMID 19447831.
^ Varela MC, Krepischi-Santos AC, Paz JA, Knijnenburg J, Szuhai K, Rosenberg C, Koiffmann CP (2006). "A 17q21.31 microdeletion encompassing the MAPT gene in a mentally impaired patient". Cytogenet Genome Res. 114 (1): 89–92. doi:10.1159/000091934. PMID 16717456.
^ Zody MC, Jiang Z, Fung HC, Antonacci F, Hillier LW, Cardone MF, Graves TA, Kidd JM, Cheng Z, Abouelleil A, Chen L, Wallis J, Glasscock J, Wilson RK, Reily AD, Duckworth J, Ventura M, Hardy J, Warren WC, Eichler EE (2008). "Evolutionary toggling of the MAPT 17q21.31 inversion region". Nat Genet. 40 (9): 1076–83. doi:10.1038/ng.193. PMC 2684794. PMID 19165922.
^ Sharkey FH, Morrison N, Murray R, Iremonger J, Stephen J, Maher E, Tolmie J, Jackson AP (2009). "17q21.31 microdeletion syndrome: further expanding the clinical phenotype". Cytogenet Genome Res. 127 (1): 61–6. doi:10.1159/000279260. PMID 20110647.
^ Kirchhoff M, Bisgaard AM, Duno M, Hansen FJ, Schwartz M (2007). "A 17q21.31 microduplication, reciprocal to the newly described 17q21.31 microdeletion, in a girl with severe psychomotor developmental delay and dysmorphic craniofacial features". Eur J Med Genet. 50 (4): 256–63. doi:10.1016/j.ejmg.2007.05.001. PMID 17576104.
^ "Koolen de Vries syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov (jezik: engleski). Pristupljeno 11. 3. 2018.

Dopunska literatura uredi

Tan TY, Aftimos S, Worgan L, Susman R, Wilson M, Ghedia S, et al. (2009). "Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome". J Med Genet. 46 (7): 480–9. doi:10.1136/jmg.2008.065391. PMID 19447831.
Sharkey FH, Morrison N, Murray R, Iremonger J, Stephen J, Maher E, et al. (2009). "17q21.31 microdeletion syndrome: further expanding the clinical phenotype". Cytogenet Genome Res. 127 (1): 61–6. doi:10.1159/000279260. PMID 20110647.
Wright EB, Donnai D, Johnson D, Clayton-Smith J (2011). "Cutaneous features in 17q21.31 deletion syndrome: a differential diagnosis for cardio-facio-cutaneous syndrome". Clin Dysmorphol. 20 (1): 15–20. doi:10.1097/MCD.0b013e32833e8f1e. PMC 3000393. PMID 21084979.
Rao PN, Li W, Vissers LE, Veltman JA, Ophoff RA (2010). "Recurrent inversion events at 17q21.31 microdeletion locus are linked to the MAPT H2 haplotype". Cytogenet Genome Res. 129 (4): 275–9. doi:10.1159/000315901. PMC 3202913. PMID 20606400.

Vanjski linkovi uredi

Šablon:DECIPHER
Orphanet entry for 17q21.31 microdeletion syndrome

Šablon:Hromosomske nenormalnosti

[pmid16906162-1] Sharp AJ, Hansen S, Selzer RR, et al. (septembar 2006). "Discovery of previously unidentified genomic disorders from the duplication architecture of the human genome". Nat. Genet. 38 (9): 1038–42. doi:10.1038/ng1862. PMID 16906162.

[pmid16906163-2] Shaw-Smith C, Pittman AM, Willatt L, Martin H, Rickman L, Gribble S, Curley R, Cumming S, Dunn C, Kalaitzopoulos D, Porter K, Prigmore E, Krepischi-Santos AC, Varela MC, Koiffmann CP, Lees AJ, Rosenberg C, Firth HV, de Silva R, Carter NP (2006). "Microdeletion encompassing MAPT at chromosome 17q21.3 is associated with developmental delay and learning disability". Nat Genet. 38 (9): 1032–7. doi:10.1038/ng1858. PMID 16906163.

[pmid16906164-3] Koolen DA, Vissers LE, Pfundt R, de Leeuw N, Knight SJ, Regan R, Kooy RF, Reyniers E, Romano C, Fichera M, Schinzel A, Baumer A, Anderlid BM, Schoumans J, Knoers NV, van Kessel AG, Sistermans EA, Veltman JA, Brunner HG, De Vries BB (2006). "A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism". Nat Genet. 38 (9): 999–1001. doi:10.1038/ng1853. PMID 16906164.

[pmid16941003-4] Lupski JR (2006). "Genome structural variation and sporadic disease traits". Nat Genet. 38 (9): 974–6. doi:10.1038/ng0906-974. PMID 16941003.

[pmid18628315-5] Koolen DA, Sharp AJ, Hurst JA, Firth HV, Knight SJ, Goldenberg A, Saugier-Veber P, Pfundt R, Vissers LE, Destrée A, Grisart B, Rooms L, Van der Aa N, Field M, Hackett A, Bell K, Nowaczyk MJ, Mancini GM, Poddighe PJ, Schwartz CE, Rossi E, De Gregori M, Antonacci-Fulton LL, McLellan MD, Garrett JM, Wiechert MA, Miner TL, Crosby S, Ciccone R, Willatt L, Rauch A, Zenker M, Aradhya S, Manning MA, Strom TM, Wagenstaller J, Krepischi-Santos AC, Vianna-Morgante AM, Rosenberg C, Price SM, Stewart H, Shaw-Smith C, Brunner HG, Wilkie AO, Veltman JA, Zuffardi O, Eichler EE, De Vries BB (2008). "Clinical and molecular delineation of the 17q21.31 microdeletion syndrome". J Med Genet. 45 (11): 710–20. doi:10.1136/jmg.2008.058701. PMC 3071570. PMID 18628315.

[pmid19447831-6] Tan TY, Aftimos S, Worgan L, Susman R, Wilson M, Ghedia S, Kirk EP, Love D, Ronan A, Darmanian A, Slavotinek A, Hogue J, Moeschler JB, Ozmore J, Widmer R, Bruno D, Savarirayan R, Peters G (2009). "Phenotypic expansion and further characterisation of the 17q21.31 microdeletion syndrome". J Med Genet. 46 (7): 480–9. doi:10.1136/jmg.2008.065391. PMID 19447831.

[pmid16717456-7] Varela MC, Krepischi-Santos AC, Paz JA, Knijnenburg J, Szuhai K, Rosenberg C, Koiffmann CP (2006). "A 17q21.31 microdeletion encompassing the MAPT gene in a mentally impaired patient". Cytogenet Genome Res. 114 (1): 89–92. doi:10.1159/000091934. PMID 16717456.

[pmid19165922-8] Zody MC, Jiang Z, Fung HC, Antonacci F, Hillier LW, Cardone MF, Graves TA, Kidd JM, Cheng Z, Abouelleil A, Chen L, Wallis J, Glasscock J, Wilson RK, Reily AD, Duckworth J, Ventura M, Hardy J, Warren WC, Eichler EE (2008). "Evolutionary toggling of the MAPT 17q21.31 inversion region". Nat Genet. 40 (9): 1076–83. doi:10.1038/ng.193. PMC 2684794. PMID 19165922.

[pmid20110647-9] Sharkey FH, Morrison N, Murray R, Iremonger J, Stephen J, Maher E, Tolmie J, Jackson AP (2009). "17q21.31 microdeletion syndrome: further expanding the clinical phenotype". Cytogenet Genome Res. 127 (1): 61–6. doi:10.1159/000279260. PMID 20110647.

[pmid17576104-10] Kirchhoff M, Bisgaard AM, Duno M, Hansen FJ, Schwartz M (2007). "A 17q21.31 microduplication, reciprocal to the newly described 17q21.31 microdeletion, in a girl with severe psychomotor developmental delay and dysmorphic craniofacial features". Eur J Med Genet. 50 (4): 256–63. doi:10.1016/j.ejmg.2007.05.001. PMID 17576104.

[:0-11] "Koolen de Vries syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov (jezik: engleski). Pristupljeno 11. 3. 2018.

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