Dismorfik Yenidoğan ve Genetik Yaklaşımlar
Özet
Bu bölüm, dismorfik yenidoğanın değerlendirilmesinde temel kavramları, konjenital anomalilerin sınıflandırılmasını ve modern genetik tanı yaklaşımlarını kapsamlı şekilde ele almaktadır. Dismorfoloji; majör ve minör anomalilerin tanımlanması, embriyolojik gelişim dönemlerinin anlaşılması ve teratojen maruziyetinin etkilerinin değerlendirilmesi açısından yenidoğan pratiğinde kritik öneme sahiptir. Konjenital anomaliler malformasyon, deformasyon, disrupsiyon ve displazi başlıkları altında incelenirken; çoklu yapısal bozukluklar sendrom, sekans, asosiasyon ve kompleks olarak sınıflandırılmaktadır. Dismorfik yenidoğana yaklaşımda ayrıntılı gebelik, aile ve yenidoğan öyküsü, üç kuşak aile ağacı, kapsamlı fizik muayene ve uygun görüntüleme yöntemleri tanısal sürecin temelini oluşturur. Günümüzde klasik sitogenetik yöntemler, FISH, kromozomal mikroarray ve yeni nesil dizileme teknolojileri genetik etiyolojinin belirlenmesinde önemli araçlar sunmaktadır. Bununla birlikte, doğru tanı için genetik testlerin dikkatli fenotipleme ve klinik değerlendirme ile birlikte yorumlanması gereklidir. Kesin tanı; tedavi, prognoz, izlem ve aileye sunulacak genetik danışmanlık açısından büyük önem taşımaktadır.
This chapter comprehensively reviews the fundamental concepts, classification systems, and modern genetic diagnostic approaches in the evaluation of the dysmorphic neonate. Dysmorphology plays a critical role in neonatal practice through the identification of major and minor anomalies, understanding embryological developmental stages, and assessing the impact of teratogenic exposures. Congenital anomalies are classified as malformations, deformations, disruptions, and dysplasias, while multiple structural abnormalities are further categorized into syndromes, sequences, associations, and complexes. A systematic approach to the dysmorphic neonate includes detailed prenatal, family, and neonatal history, three-generation pedigree analysis, thorough physical examination, and targeted imaging studies. Modern diagnostic strategies incorporate conventional cytogenetics, FISH, chromosomal microarray analysis, and next-generation sequencing technologies. Although these genomic tools significantly improve diagnostic precision, accurate diagnosis still depends on careful phenotypic assessment and comprehensive clinical interpretation. Establishing a definitive diagnosis is essential for appropriate treatment, prognosis, long-term follow-up, and genetic counseling for affected families.
Referanslar
Smith DW. Recognizable patterns of human malformation. Major problems in clinical pediatrics. 1976;7:1-497.
Jones KL, Jones MC, Del Campo M. Smith's recognizable patterns of human malformation-E-book: Elsevier Health Sciences; 2021.
Kinsner-Ovaskainen A, Lanzoni M, Garne E, et al. A sustainable solution for the activities of the European network for surveillance of congenital anomalies: EUROCAT as part of the EU Platform on Rare Diseases Registration. European Journal of Medical Genetics. 2018;61(9):513-7.
Keçeci R, Keçeci HN, Başdemirci M. Microarray Application in Newborns With Multiple Congenital Anomalies: Genotype–Phenotype Correlation. Birth Defects Research. 2025;117(7):e2509.
Elder JS, Kliegman R, Stanton B, Geme J, Schor N, Behrman R. Nelson textbook of pediatrics. Saunders; 2011.
Hoffman JI, Kaplan S. The incidence of congenital heart disease. Journal of the American college of cardiology. 2002;39(12):1890-900.
Marden PM, Smith DW, McDonald MJ. Congenital anomalies in the newborninfant, including minor variations: A study of 4,412 babies by surface examination for anomalies and buccal smear for sex chromatin. The Journal of pediatrics. 1964;64(3):357-71.
Brent RL. Environmental causes of human congenital malformations: the pediatrician’s role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics. 2004;113(Supplement_3):957-68.
Srivastava G. BOOK review: langman's medical embryology by tw sadler. Era's Journal of Medical Research. 2018;5(1):86-.
Stevenson RE, Hall JG. Human malformations and related anomalies. (No Title). 2006.
Moore KL, Persaud TVN, Torchia MG. The developing Human-E-Book: the developing human-E-Book: Elsevier Health Sciences; 2018.
Strachan T, Read AP. Human molecular genetics/Tom Strachan and Andrew Read. New York: Garland Science; 2011.
Willard HF. Thompson & Thompson genetics in medicine: Saunders; 2001.
McKusick V. OMIM™: Online Mendelian Inheritance in Man™[database]. Johns Hopkins University. 2003.
Carey JC, Allanson JE, Hennekam RC, Biesecker LG. Standard terminology for phenotypic variations: the elements of morphology project, its current progress, and future directions. Human Mutation. 2012;33(5):781-6.
Solomon BD. Vacterl/vater association. Orphanet journal of rare diseases. 2011;6(1):56.
Basel D. Dysmorphology in a genomic era. Clinics in perinatology. 2020;47(1):15-23.
Kim AY, Bodurtha JN. Dysmorphology. Pediatrics in review. 2019;40(12):609-18.
Clayton-Smith J. Assessment of the dysmorphic infant. Infant. 2008;4(6):206-10.
Gurovich Y, Hanani Y, Bar O, et al. Identifying facial phenotypes of genetic disorders using deep learning. Nature medicine. 2019;25(1):60-4.
Hsieh T-C, Bar-Haim A, Moosa S, et al. GestaltMatcher facilitates rare disease matching using facial phenotype descriptors. Nature genetics. 2022;54(3):349-57.
Echeverry-Quiceno LM, Candelo E, Gómez E, et al. Population-specific facial traits and diagnosis accuracy of genetic and rare diseases in an admixed Colombian population. Scientific Reports. 2023;13(1):6869.
Corrin S. “Gardner and Sutherland’s chromosome abnormalities and genetic counseling” by RJ McKinlay Gardner, David J. Amor. Oxford University Press. Springer; 2018.
McGowan-Jordan J, Hastings RJ, Moore S. Iscn 2020: An International System for Human Cytogenomic Nomenclature (2020). Reprint of'Cytogenetic and Genome Research 2020, Vol. 160, No. 7-8': Karger Medical and Scientific Publishers; 2020.
Liehr T, Starke H, Weise A, Lehrer H, Claussen U. Multicolor FISH probe sets and their applications. Histology and histopathology. 2004;19(1):229-37.
Restriction FG. ACOG Practice Bulletin. Obstet Gynecol. 2021;137:16-28.
Speicher MR, Carter NP. The new cytogenetics: blurring the boundaries with molecular biology. Nature reviews genetics. 2005;6(10):782-92.
Flint J, Wilkie AO, Buckle VJ, Winter RM, Holland AJ, McDermid HE. The detection of subtelomeric chromosomal rearrangements in idiopathic mental retardation. Nature genetics. 1995;9(2):132-40.
de Vries BB, White S, Knight S, et al. Clinical studies on submicroscopic subtelomeric rearrangements: a checklist. Journal of medical genetics. 2001;38(3):145-50.
Miller DT, Adam MP, Aradhya S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. The American Journal of Human Genetics. 2010;86(5):749-64.
Pinkel D, Albertson DG. Array comparative genomic hybridization and its applications in cancer. Nature genetics. 2005;37(Suppl 6):S11-S7.
Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in medicine. 2015;17(5):405-23.
Riggs ER, Andersen EF, Cherry AM, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Elsevier; 2020.
Metzker ML. Sequencing technologies—the next generation. Nature reviews genetics. 2010;11(1):31-46.
Goodwin S, McPherson JD, McCombie WR. Coming of age: ten years of next-generation sequencing technologies. Nature reviews genetics. 2016;17(6):333-51.
Yang M, Kim JA, Jo HS, et al. Diagnostic utility of whole genome sequencing after negative karyotyping/chromosomal microarray in infants born with multiple congenital anomalies. Journal of Korean Medical Science. 2024;39(36).
Kingsmore SF, Cakici JA, Clark MM, et al. A randomized, controlled trial of the analytic and diagnostic performance of singleton and trio, rapid genome and exome sequencing in ill infants. The American Journal of Human Genetics. 2019;105(4):719-33.
Rehm HL, Bale SJ, Bayrak-Toydemir P, et al. ACMG clinical laboratory standards for next-generation sequencing. Genetics in medicine. 2013;15(9):733-47.
Collins FS, Morgan M, Patrinos A. The Human Genome Project: lessons from large-scale biology. Science. 2003;300(5617):286-90.
Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proceedings of the national academy of sciences. 1977;74(12):5463-7.
