Der Gynäkologe

, Volume 45, Issue 1, pp 35–40 | Cite as

Pränataldiagnostik

Erweiterung durch genetische Erkenntnisse
Leitthema

Zusammenfassung

Die pränatale Diagnostik ist als verbindendes Spezialgebiet sowohl der Frauenheilkunde und Geburtshilfe als auch der Humangenetik zu sehen. Sie stützt sich einserseits auf die detaillierte sonographische Diagnostik im ersten und zweiten Trimenon (einschließlich der individualisierten Risikostratifizierung) mittels modernster Technik (wie hochauflösende Ultraschallsysteme mit Farbdoppler, 3D/4D-Technologie mit Volumendarstellung fetaler Strukturen),andererseits auf die spezielle vorgeburtliche genetische Untersuchung und Beratung bei entsprechenden Fragestellungen den Feten bzw. ratsuchende Paare betreffend. Dabei ist der Stellenwert der konventionellen Zytogenetik als Goldstandard im Rahmen der Chromosomenanalyse unstrittig. Neuere Techniken, wie molekulargenetische Untersuchungen zur Abklärung bestimmter genetischer Erkrankungen (z. B. Stoffwechselstörungen wie Mukoviszidose), die Untersuchung von Markerchromosomen, Array-CGH bei unklaren Krankheitsbildern (z. B. fetale Retardierung) oder Methylierungsstörungen bei Imprinting-Syndromen spielen dabei zunehmend eine Rolle für eine optimale individuelle Beratung in Bezug auf die Prognose bei auffälligem Befund nach pränataler Diagnostik.

Schlüsselwörter

Konventionelle Zytogenetik Chordozentese Methylierungsstörung Molekulargenetische Untersuchungen Zellfreie fetale DNA 

Prenatal diagnostics

Enhancement through genetic findings

Abstract

Prenatal diagnosis as a link between obstetrics/gynecology and human genetics is based on targeted sonographic diagnosis during the first and second trimester (including customized risk assessment) by using modern ultrasound equipment (color Doppler, volume rendering via 3D/4D technology) and antenatal genetic testing and counseling pertaining to distinct problems of either the fetus or concerned couples. Undoubtedly, conventional cytogenetics remains the first-line diagnostic tool for chromosomal analyses. Recent advances, such as molecular genetics for the targeted diagnosis of metabolic disorders (e.g., cystic fibrosis), the presence of marker chromosomes, array-based CGH to identify chromosomal imbalances in cases of unknown fetal abnormalities, or methylation disorders (imprinting syndromes), are gaining more and more importance for optimized individual counseling of the patient with regard to the prognosis following an abnormal prenatal diagnosis.

Keywords

Conventional cytogenetics Cordozentesis Methylation disorders Molecular genetic analyses Cell-free fetal DNA 

Literatur

  1. 1.
    BAQ (2010) www.BAQ-Bayern.deGoogle Scholar
  2. 2.
    Snijders RJ et al (1998) UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group. Lancet 352(9125):343–346PubMedCrossRefGoogle Scholar
  3. 3.
    Geipel A et al (2007) Changing attitudes towards non-invasive aneuploidy screening at advanced maternal age in a German tertiary care center. Ultraschall Med 28(1):67–70PubMedCrossRefGoogle Scholar
  4. 4.
    Abele H et al (2011) Impact of the maternal age-related risk in first-trimester combined screening for trisomy 21. Fetal Diagn Ther 30(2):135–140PubMedCrossRefGoogle Scholar
  5. 5.
    Luthgens K et al (2011) Cross-validation of the first trimester screening algorithm of the FMF London on 38,700 pregnancies in Germany. Ultraschall Med 32(4):367–372PubMedCrossRefGoogle Scholar
  6. 6.
    Viot G (2002) Confined placental mosaicism: definition, consequences and outcome. J Gynecol Obstet Biol Reprod (Paris) 31(Suppl 1):270–274Google Scholar
  7. 7.
    Tabor A, Alfirevic Z (2010) Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther 27(1):1–7PubMedCrossRefGoogle Scholar
  8. 8.
    Miny P et al (2003) Genetic testing in pregnancy. Ther Umsch 60(8):455–461PubMedCrossRefGoogle Scholar
  9. 9.
    Srebniak M et al (2011) Application of SNP array for rapid prenatal diagnosis: implementation, genetic counselling and diagnostic flow. Eur J Hum Genet 19(12):1230−1237PubMedCrossRefGoogle Scholar
  10. 10.
    Gagnon A et al (2009) Evaluation of prenatally diagnosed structural congenital anomalies. J Obstet Gynaecol Can 31(9):875–881, 882–889PubMedGoogle Scholar
  11. 11.
    Choufani S, Shuman C, Weksberg R (2010) Beckwith-Wiedemann syndrome. Am J Med Genet C Semin Med Genet 154C(3):343–354PubMedCrossRefGoogle Scholar
  12. 12.
    Reish O et al (2002) Wiedemann-Beckwith syndrome: further prenatal characterization of the condition. Am J Med Genet 107(3):209–213PubMedCrossRefGoogle Scholar
  13. 13.
    Kotzot D (2008) Prenatal testing for uniparental disomy: indications and clinical relevance. Ultrasound Obstet Gynecol 31(1):100–105PubMedCrossRefGoogle Scholar
  14. 14.
    Hirasawa R, Feil R (2010) Genomic imprinting and human disease. Essays Biochem 48(1):187–200PubMedCrossRefGoogle Scholar
  15. 15.
    Amor DJ, Halliday J (2008) A review of known imprinting syndromes and their association with assisted reproduction technologies. Hum Reprod 23(12):2826–2834PubMedCrossRefGoogle Scholar
  16. 16.
    Eckmann-Scholz C et al (2011) Normal prenatal ultrasound findings in a case with de novo mosaic small supernumerary marker chromosome 18 – how to counsel? J Matern Fetal Neonatal MedGoogle Scholar
  17. 17.
    Liehr T, Weise A (2007) Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics. Int J Mol Med 19(5):719–731PubMedGoogle Scholar
  18. 18.
    Aagaard-Tillery KM, Malone FD, Nyberg DA et al (2009) First and second trimester evaluation of risk research consortium. Role of second-trimester genetic sonography after Down syndrome screening. Obstet Gynecol 114:1189–1196PubMedCrossRefGoogle Scholar
  19. 19.
    American College of Obstetricians and Gynecologists (2009) ACOG Committee Opinion No. 446: array comparative genomic hybridization in prenatal diagnosis. Obstet Gynecol 114:1161–1163CrossRefGoogle Scholar
  20. 20.
    Bartholdi D (2008) Medizinische Genetik: Copy number variants (CNV). Schweiz Med Forum 8:1007–1008Google Scholar
  21. 21.
    Boyd PA, DeVigan C, Khoshnood B et al (2008) Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down’s syndrome. BJOG 115:689–696PubMedCrossRefGoogle Scholar
  22. 22.
    D’Amours G, Kibar Z, Mathonnet G et al (2011) Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype. Clin Genet doi:10.1111/j.1399-0004.2011.01687.x.Google Scholar
  23. 23.
    DeVore GR (2010) Genetic sonography: the historical and clinical role of fetal echocardiography. Ultrasound Obstet Gynecol 35:509–521PubMedCrossRefGoogle Scholar
  24. 24.
    DeVore GR, Romero R (2003) Genetic sonography: an option for women of advanced maternal age with negative triple-marker maternal serum screening results. J Ultrasound Med 22:1191–1119PubMedGoogle Scholar
  25. 25.
    Friedman JM (2009) High-resolution array genomic hybridization in prenatal diagnosis. Prenat Diagn 29:20–28PubMedCrossRefGoogle Scholar
  26. 26.
    Hahn S, Lapaire O, Tercanli S et al (2011) Determination of fetal chromosome aberrations from fetal DNA in maternal blood: has the challenge finally been met? Expert Rev Mol Med 13:e16PubMedCrossRefGoogle Scholar
  27. 27.
  28. 28.
    Lapaire O, Hahn S, Holzgreve W et al (2005) Die nichtinvasive Pränataldiagnostik aus dem mütterlichen Blut: schrittweiser Einzug in den klinischen Alltag. J Reproduktionsmed Endokrinol 2:272–277Google Scholar
  29. 29.
    Lo YM, Corbetta N, Chamberlain PF et al (1997) Presence of fetal DNA in maternal plasma and serum. Lancet 350:485–487PubMedCrossRefGoogle Scholar
  30. 30.
    Maya I, Davidov B, Gershovitz L et al (2010) Diagnostic utility of array-based comparative genomic hybridization (aCGH) in a prenatal setting. Prenat Diagn 30:1131–1137PubMedCrossRefGoogle Scholar
  31. 31.
    Maymon R, Zimerman AL, Weinraub Z et al (2008) Correlation between nuchal translucency and nuchal skin-fold measurements in Down syndrome and unaffected fetuses. Ultrasound Obstet Gynecol 32:501–505PubMedCrossRefGoogle Scholar
  32. 32.
    Merz E, Eichhorn KH, Hansmann M et al (2002) Qualitätsanforderungen an die weiterführende differenzialdiagnostische Ultraschalluntersuchung in der pränatalen Diagnostik (= DEGUM-Stufe II) im Zeitraum 18 bis 22 Schwangerschaftswochen. Ultraschall Med 23:11–12PubMedCrossRefGoogle Scholar
  33. 33.
    Nyberg DA, Souter VL, El-Bastawissi A et al (2001) Isolated sonographic markers for detection of fetal Down syndrome in the second trimester of pregnancy. J Ultrasound Med 20:1053–1063PubMedGoogle Scholar
  34. 34.
    Papageorgiou EA, Karagrigoriou A, Tsaliki E et al (2011) Fetal-specific DNA methylation ratio permits noninvasive prenatal diagnosis of trisomy 21. Nat Med 17:510–513PubMedCrossRefGoogle Scholar
  35. 35.
    Rozenberg P, Bussières L, Chevret S et al (2006) Screening for Down syndrome using first-trimester combined screening followed by second-trimester ultrasound examination in an unselected population. Am J Obstet Gynecol 195:1379–1387PubMedCrossRefGoogle Scholar
  36. 36.
    Salomon LJ, Alfirevic Z, Berghella V et al (2011) Practice guidelines for performance of the routine mid-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol 37:116–126PubMedCrossRefGoogle Scholar
  37. 37.
    Schwerdtfeger R (2011) Probleme der vorgeburtlichen Diagnostik. In: Duttge G, Engel W, Zoll B (Hrsg) Das Gendiagnostikgesetz im Spannungsfeld von Humangenetik und Recht. Göttinger Schriften zum Medizinrecht, Bd. 11, Universitätsverlag, Göttingen, S 53–39Google Scholar
  38. 38.
    Shaffer LG, Bui TH (2007) Molecular cytogenetic and rapid aneuploidy detection methods in prenatal diagnosis. Am J Med Genet C Semin Med Genet 145C:87–98PubMedCrossRefGoogle Scholar
  39. 39.
    Smith-Bindman R, Hosmer WD, Feldstein VA et al (2001) Second trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis. JAMA 285:1044–1055PubMedCrossRefGoogle Scholar
  40. 40.
    Solinas-Toldo S, Lampel S, Stilgenbauer S et al (1997) Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer 20:399–407PubMedCrossRefGoogle Scholar
  41. 41.
    Van den Veyver IB, Patel A, Shaw CA et al (2009) Clinical use of array comparative genomic hybridization (aCGH) for prenatal diagnosis in 300 cases. Prenat Diagn 29:29–39CrossRefGoogle Scholar
  42. 42.
    Vissers LE, Veltman JA, Kessel AG van et al (2005) Identification of disease genes by whole genome CGH arrays. Hum Mol Genet 14:R215–R223PubMedCrossRefGoogle Scholar
  43. 43.
    Weise A, Liehr T (2008) Fluorescence in situ hybridization for prenatal screening of chromosomal aneuploidies. Expert Rev Mol Diagn 8:355–357PubMedCrossRefGoogle Scholar
  44. 44.
    Wieacker D, Steinhard P (2010) The prenatal diagnosis of genetic diseases. Dtsch Arztebl 107 (48):857−862Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Bereich Pränatalmedizin und Spezielle Geburtshilfe, Klinik für Frauenheilkunde und GeburtshilfeUniversitätsklinikum Schleswig-Holstein, Campus LübeckLübeckDeutschland
  2. 2.Bereich Pränatale Diagnostik, Klinik für Gynäkologie und Geburtshilfe, FrauenklinikUniversitätsklinikum Schleswig-Holstein, Campus KielKielDeutschland

Personalised recommendations