Nörogenetik Hastalıklarda Klinik Yaklaşım ve Yönetim
Özet
Genetik bozukluklar; zihinsel yetersizlik ve yaygın gelişimsel gerilik gibi nörolojik tabloların etyolojisinde merkezi bir rol oynamaktadır. Hastaların klinik değerlendirmesi, ayrıntılı öykü ve muayene ile başlayıp, kromozom analizi ve mikrodizin gibi geleneksel yöntemlerden tüm ekzom dizileme gibi ileri moleküler tekniklere kadar uzanan kapsamlı bir tanısal süreci gerektirir. Down, Patau ve Klinefelter sendromları gibi çeşitli kromozomal anomaliler ve mikrodelesyon/duplikasyon sendromları, farklı fenotipik özelliklerle karakterize olup, tanısal süreçte çok disiplinli bir yaklaşımı zorunlu kılar. Güncel moleküler genetik analizler, önceki yöntemlerle tanımlanamayan vakaların aydınlatılmasında kritik bir öneme sahiptir.
Genetic disorders play a central role in the etiology of neurological conditions such as intellectual disability and global developmental delay. Clinical assessment requires a comprehensive diagnostic process starting with detailed history and physical examination, followed by advanced molecular techniques ranging from traditional chromosomal analysis to whole-exome sequencing. Various chromosomal anomalies, such as Down, Patau, and Klinefelter syndromes, along with diverse microdeletion and duplication syndromes, present unique phenotypic characteristics that demand a multidisciplinary diagnostic approach. Modern molecular genetic tools are increasingly vital for identifying the underlying genetic causes in cases that remain undiagnosed by standard testing.
Referanslar
Schalock R.L, Luckasson R.A, Shogren K.A, et al. The renaming of mental retardation: understanding the change to the term intellectual disability. Intellect Dev Disabil. 2007;45(2):116–124.
Shevell M, Ashwal S, Donley D, et al. Practice parameter: evaluation of the child with global developmental delay: report of the quality standards subcommittee of the American Academy of neurology and the practice cof the child neurology society. Neurology. 2003;60(3):367–380.
Moeschler J.B, Shevell M. Clinical genetic evaluation of the child with mental retardation or developmental delays. Pediatrics. 2006;117(6):2304– 2316.
Kliegmann MRM, St Geme JW, et al. Nelson Textbook of Pediatrics. 21th ed. Philadelphia, PA: Elsevier; 2020.
Thuline, H. C., Pueschel, S. M. Cytogenetics in Down syndrome. In: Pueschel, S. M.; Rynders, J. E.: Down Syndrome. Advances in Biomedicine and the Behavioral Sciences. Cambridge: Ware Press (pub.) 1982. P. 133.
Hook, E. G. Epidemiology of Down syndrome. In: Pueschel, S. M.; Rynders, J. E. (eds.): Down Syndrome. Advances in Biomedicine and the Behavioral Sciences. Cambridge: Ware Press (pub.) 1982. P. 11 only.
Mikkelsen, M. Down's syndrome cytogenetic epidemiology. Hereditas 86: 45-59, 1977. [PubMed: 143464, related citations] [Full Text]
Lakovschek IC, Streubel B, Ulm B. Natural outcome of trisomy 13, trisomy 18, and triploidy after prenatal diagnosis. Am J Med Genet A 2011; 155A:2626.
Ratcliffe SG, Jenkins J, Teague P. Cognitive and behavioural development of the 47,XYY child. In: Berch DB, Bender BG, editors. Sex chromosome abnormalities and behavior: psychological studies. Boulder, CO, USA: Westview Press; 1990. pp. 161–84.
Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A, Klinefelter ItaliaN Group (KING) (2016) Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Invest Sep 19 [Epub ahead of print] Review. doi:10.1007/s40618-016-0541-6
Nussbaum RL, McInnes RR, Willard HF. Thompson & Thompson Genetics in Medicine. 8th edition. Elsevier: Philadelphia, PA, 2007.
Weise A, Mrasek K, Klein E, Mulatinho MV, Llerena Jr JC, Hardekopf D, et al (2012) Microdeletion and microduplication syndromes. J Histochem Cytochem 60:346-58
Du Q, de la Morena MT and van Oers NSC (2020) The Genetics and Epigenetics of 22q11.2 Deletion Syndrome. Front. Genet. 10:1365.
Guna, A., Butcher, N. J., Bassett, A. S. (2015). Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms. J. Neurodev. Disord. 7, 1–16.
Mcdonald-Mcginn, D. M., Fahiminiya, S., Revil, T., Nowakowska, B. A., Suhl, J., Bailey, A., et al. (2013). Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS. J. Med. Genet. 50, 80–90.
Edelmann L, Pandita RK, Morrow BE. Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome. Am. J. Hum. Genet. 1999; 64:1076–1086.
McDonald-McGinn DM, et al. Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net! Genet. Med. 2001; 3:23–29.
Carelle-Calmels, N., Saugier-Veber, P., Girard-Lemaire, F., Rudolf, G., Doray, B., Guerin, E., et al. Genetic compensation in a human genomic disorder. New Eng. J. Med. 360: 1211-1216, 2009.
Butler, M. G. Prader-Willi syndrome: current understanding of cause and diagnosis. Am. J. Med. Genet. 35: 319-332, 1990.
Bird LM. Angelman syndrome: a review of clinical and molecular aspects. Appl Clin Genet. 2014; 7:93–104.
Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 1997; 15:70.
Matsuura T, Sutcliffe JS, Fang P, et al. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet 1997; 15:74.
Sahoo T, Peters SU, Madduri NS, et al. Microarray based comparative genomic hybridization testing in deletion bearing patients with Angelman syndrome: genotype-phenotype correlations. J Med Genet 2006; 43:512.
Saitoh S, Buiting K, Cassidy SB, et al. Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation. Am J Med Genet 1997; 68:195.
Malcolm S, Clayton-Smith J, Nichols M, et al. Uniparental paternal disomy in Angelman's syndrome. Lancet 1991; 337:694.
Buiting K, Gross S, Lich C, et al. Epimutations in Prader-Willi and Angelman syndromes: a molecular study of 136 patients with an imprinting defect. Am J Hum Genet 2003; 72:571.
Buiting K, Lich C, Cottrell S, et al. A 5-kb imprinting center deletion in a family with Angelman syndrome reduces the shortest region of deletion overlap to 880 bp. Hum Genet 1999; 105:665.
Abaied L, Trabelsi M, Chaabouni M, et al. A novel UBE3A truncating mutation in large Tunisian Angelman syndrome pedigree. Am J Med Genet A 2010; 152A:141.
vanTuinen P, Dobyns WB, Rich DC, et al. Molecular detection of microscopic and submicroscopic deletions associated with Miller-Dieker syndrome. Am J Hum Genet 1988; 43:587.
Jones KL, Gilbert EF, Kaveggia EG, Opitz JM. The MIller-Dieker syndrome. Pediatrics 1980; 66:277.
Dhellemmes C, Girard S, Dulac O, et al. Agyria--pachygyria and Miller-Dieker syndrome: clinical, genetic and chromosome studies. Hum Genet 1988; 79:163.
Oostra BA, de Rijk-van Andel JF, Eussen HJ, et al. DNA analysis in patients with lissencephaly type I and other cortical dysplasias. Am J Med Genet 1991; 40:383.
Dobyns WB, Curry CJ, Hoyme HE, Turlington L, Ledbetter DH. Clinical and molecular diagnosis of Miller-Dieker syndrome. Am J Hum Genet. 1991;48:584–94.
Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991; 65:905.
Rooms L, Kooy RF. Advances in understanding fragile X syndrome and related disorders. Curr Opin Pediatr 2011; 23:601.
Hagerman RJ, Berry-Kravis E, Kaufmann WE, et al. Advances in the treatment of fragile X syndrome. Pediatrics 2009; 123:378.
De Boulle K, Verkerk AJ, Reyniers E, et al. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet 1993; 3:31.
Coffee B, Ikeda M, Budimirovic DB, et al. Mosaic FMR1 deletion causes fragile X syndrome and can lead to molecular misdiagnosis: a case report and review of the literature. Am J Med Genet A 2008; 146A:1358.
Latham GJ, Coppinger J, Hadd AG, Nolin SL. The role of AGG interruptions in fragile X repeat expansions: a twenty-year perspective. Front Genet 2014; 5:244.
Hunter, J., Berry-Kravis, E., Hipp, H., Todd, P., 2019. FMR1 disorders. In: Adam,M.P.A.H., Pagon, R.A. (Eds.), GeneReviews®[Internet]. University of Washington,Seattle, Seattle (WA).
Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol 2010; 68:944.
Zappella M. The Rett girls with preserved speech. Brain Dev 1992; 14:98.
Russo S, Marchi M, Cogliati F, et al. Novel mutations in the CDKL5 gene, predicted effects and associated phenotypes. Neurogenetics 2009; 10:241.
Epperson MV, Haws ME, Standridge SM, Gilbert DL. An Atypical Rett Syndrome Phenotype Due to a Novel Missense Mutation in CACNA1A. J Child Neurol 2018; 33:286.
Ariani F, Hayek G, Rondinella D, et al. FOXG1 is responsible for the congenital variant of Rett syndrome. Am J Hum Genet 2008; 83:89.
Anazi S, Maddirevula S, Faqeih E, et al. Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. Mol Psychiatry. 2017;22(4):615–624.
