Skip to main content
SpringerLink
Log in

Pränataldiagnostik bei fetaler Mikrozephalie

Prenatal diagnosis of fetal microcephaly

  • Schwerpunktthema: Mikrozephalie
  • Published:
medizinische genetik

Zusammenfassung

Diese Übersichtsarbeit behandelt die Mikrozephalie (MZ) aus der Perspektive der pränatalen Diagnostik. Eine MZ wird bei einem Kopfumfang unter der dritten Standardabweichung für das Gestationsalter vermutet. Diese Verdachtsdiagnose kann aus einem falschen Gestationsalter oder einer falsche Messung resultieren oder infolge einer Reihe häufiger Ätiologien wie offene Spina bifida, Enzephalozele, Holoprosenzephalie, Infektion, Aneuploidie, seltener auch Ursachen wie einer primären oder syndromalen MZ entstehen. Typische Ultraschallzeichen einer fetalen MZ sind die flache Stirn, der kleine Frontallappen, das reduzierte Gyrierungsmuster mit einem kurzen Balken, eine Pseudo-Kraniosynostose, ein dilatierter Subarachnoidalraum und oft eine Diskrepanz zwischen Kopf- und Bauchumfang. Mitunter kann eine schwere MZ schon in der Mitte der Schwangerschaft entdeckt werden, aber die meisten Formen fallen erst im III. Trimenon bzw. nach der Geburt auf. Die diagnostische Abklärung sollte auch das Angebot genetischer Untersuchungen einschließen, um monogen vererbte Formen mit hohem Wiederholungsrisiko z. B. bei autosomal-rezessiver Vererbung zu identifizieren. Die Arbeit diskutiert pränatalmedizinische und genetisch-diagnostische Abklärungsschritte bei fetaler MZ, die in Kombination mit den neuen genetischen Untersuchungstechniken hoffentlich in Zukunft zu einer höheren Aufklärungsrate führen werden.

Abstract

This review article discusses microcephaly (MC) from the perspective of prenatal diagnosis. MC is defined as a head circumference measurement below the − 3 standard deviation for gestational age. Suspected MC may inadvertently result from an incorrect fetal age or measurement, but may also be due to common etiologies such as open spina bifida, encephalocele, holoprosencephaly, infection, aneuploidy or one of the rare true or syndromic microcephalies. Typical ultrasound signs of fetal MC are the flat forehead, the small anterior lobe, the reduced gyral pattern with a short corpus callosum, pseudo-craniosynostosis, dilated subarachnoid space, and often a discrepant head to abdominal circumference. Some forms of severe MC may be evident in midtrimester, while most cases of MC are not detectable until the third trimester or after birth. Diagnostic assessment should include the offer of a genetic workup to identify monogenic forms with a high risk of recurrence, e.g., due to autosomal recessive inheritance. The paper discusses prenatal and genetic diagnostic algorithms in pregnancies with fetal MC, which, in combination with new genetic tools, will hopefully also increase the yield of the diagnostic genetic workup.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6

Literatur

  1. Abuelo D (2007) Microcephaly syndromes. Semin Pediatr Neurol 14:118–127

    Article  PubMed  Google Scholar 

  2. Adachi Y, Poduri A, Kawaguch A, Yoon G, Salih MA, Yamashita F, Walsh CA, Barkovich AJ (2011) Congenital microcephaly with a simplified gyral pattern: associated findings and their significance. AJNR Am J Neuroradiol 32:1123–1129

    Article  PubMed  CAS  Google Scholar 

  3. Bahlmann F, Reinhard I, Schramm T, Geipel A, Gembruch U, von Kaisenberg CS, Schmitz R, Stupin J, Chaoui R, Karl K, Kalache K, Faschingbauer F, Ponnath M, Rempen A, Kozlowski P (2015) Cranial and cerebral signs in the diagnosis of spina bifida between 18 and 22 weeks of gestation: a German multicentre study. Prenat Diagn 35:228–235

    Article  PubMed  CAS  Google Scholar 

  4. Barkovich AJ, Guerrini R, Kuzniecky RI, Jackson GD, Dobyns WB (2012) A developmental and genetic classification for malformations of cortical development: update 2012. Brain 135:1348–1369

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bromley B, Benacerraf BR (1995) Difficulties in the prenatal diagnosis of microcephaly. J Ultrasound Med 14:303–306

    PubMed  CAS  Google Scholar 

  6. Chaoui R, Heling KS, Kainer F, Karl K (2012) [Fetal neurosonography using 3-dimensional multiplanar sonography]. Z Geburtshilfe Neonatol 216:54–62

    Article  PubMed  CAS  Google Scholar 

  7. Fallet-Bianco C, Laquerriere A, Poirier K, Razavi F, Guimiot F, Dias P, Loeuillet L, Lascelles K, Beldjord C, Carion N, Toussaint A, Revencu N, Addor MC, Lhermitte B, Gonzales M, Martinovich J, Bessieres B, Marcy-Bonniere M, Jossic F, Marcorelles P, Loget P, Chelly J, Bahi-Buisson N (2014) Mutations in tubulin genes are frequent causes of various foetal malformations of cortical development including microlissencephaly. Acta Neuropathol Commun 2:69

    Article  PubMed  PubMed Central  Google Scholar 

  8. Goldstein I, Reece EA, Pilu G, O’Connor TZ, Lockwood CJ, Hobbins JC (1988) Sonographic assessment of the fetal frontal lobe: a potential tool for prenatal diagnosis of microcephaly. Am J Obstet Gynecol 158:1057–1062

    Article  PubMed  CAS  Google Scholar 

  9. von der Hagen M, Pivarcsi M, Liebe J, von Bernuth H, Didonato N, Hennermann JB, Buhrer C, Wieczorek D, Kaindl AM (2014) Diagnostic approach to microcephaly in childhood: a two-center study and review of the literature. Dev Med Child Neurol 56:732–741

    Article  PubMed  Google Scholar 

  10. den Hollander NS, Wessels MW, Los FJ, Ursem NT, Niermeijer MF, Wladimiroff JW (2000) Congenital microcephaly detected by prenatal ultrasound: genetic aspects and clinical significance. Ultrasound Obstet Gynecol 15:282–287

    Article  Google Scholar 

  11. ISUOG (2007) Sonographic examination of the fetal central nervous system: guidelines for performing the ‘basic examination’ and the ‘fetal neurosonogram’. Ultrasound Obstet Gynecol 29:109–116

    Article  Google Scholar 

  12. Jaffe M, Tirosh E, Oren S (1987) The dilemma in prenatal diagnosis of idiopathic microcephaly. Dev Med Child Neurol 29:187–189

    Article  PubMed  CAS  Google Scholar 

  13. Johnsen SL, Wilsgaard T, Rasmussen S, Sollien R, Kiserud T (2006) Longitudinal reference charts for growth of the fetal head, abdomen and femur. Eur J Obstet Gynecol Reprod Biol 127(2):172–185

    Article  PubMed  Google Scholar 

  14. Kaindl AM (2014) Autosomal recessive primary microcephalies (MCPH). Eur J Paediatr Neurol 18:547–548

    Article  PubMed  Google Scholar 

  15. Karl K, Kainer F, Heling KS, Chaoui R (2011) Fetal neurosonography: extended examination of the CNS in the fetus. Ultraschall Med 32:342–361

    Article  PubMed  CAS  Google Scholar 

  16. Karl K, Benoit B, Entezami M, Heling KS, Chaoui R (2012) Small biparietal diameter in fetuses with spina bifida on 11–13-week and mid-gestation ultrasound. Ultrasound Obstet Gynecol 40:140–144

    Article  PubMed  CAS  Google Scholar 

  17. Karl K, Heling KS, Chaoui R (2015) Ultrasound of the Fetal Veins Part 3: the Fetal Intracerebral Venous System. Ultraschall Med. doi:10.1055/s-0035-1553284

  18. Kurmanavicius J, Wright EM, Royston P, Wisser J, Huch R, Huch A, Zimmermann R (1999) Fetal ultrasound biometry: 1. Head reference values. Br J Obstet Gynaecol 106(2):126–135

    Article  PubMed  CAS  Google Scholar 

  19. Malinger G, Lerman-Sagie T, Watemberg N, Rotmensch S, Lev D, Glezerman M (2002) A normal second-trimester ultrasound does not exclude intracranial structural pathology. Ultrasound Obstet Gynecol 20:51–56

    Article  PubMed  CAS  Google Scholar 

  20. Mercier S, Dubourg C, Belleguic M, Pasquier L, Loget P, Lucas J, Bendavid C, Odent S (2010) Genetic counseling and „molecular“ prenatal diagnosis of holoprosencephaly (HPE). Am J Med Genet C Semin Med Genet 154C:191–196

    Article  PubMed  Google Scholar 

  21. Napolitano R, Maruotti GM, Quarantelli M, Martinelli P, Paladini D (2009) Prenatal diagnosis of Seckel Syndrome on 3-dimensional sonography and magnetic resonance imaging. J Ultrasound Med 28:369–374

    PubMed  Google Scholar 

  22. Online Mendelian Inheritance in Man O (2014) Seckel Syndrome 1; SCKL1. Johns Hopkins University, Baltimore. http://omim.org/

  23. Persutte WH (1998) Microcephaly‐no small deal. Ultrasound Obstet Gynecol 11:317–318

    Article  PubMed  CAS  Google Scholar 

  24. Pilu G, Malinger G (2013) Microcephaly. In: Visual Encyclopedia of Ultrasound in Obstetrics and Gynecology. http://www.visuog.com

  25. Pilu G, Falco P, Milano V, Perolo A, Bovicelli L (1998) Prenatal diagnosis of microcephaly assisted by vaginal sonography and power Doppler. Ultrasound Obstet Gynecol 11:357–360

    Article  PubMed  CAS  Google Scholar 

  26. Pilu G, Ghi T, Carletti A, Segata M, Perolo A, Rizzo N (2007) Three-dimensional ultrasound examination of the fetal central nervous system. Ultrasound Obstet Gynecol 30:233–245

    Article  PubMed  CAS  Google Scholar 

  27. Poulton CJ, Schot R, Seufert K, Lequin MH, Accogli A, Annunzio GD, Villard L, Philip N, de Coo R, Catsman-Berrevoets C, Grasshoff U, Kattentidt-Mouravieva A, Calf H, de Vreugt-Gronloh E, van Unen L, Verheijen FW, Galjart N, Morris-Rosendahl DJ, Mancini GM (2014) Severe presentation of WDR62 mutation: is there a role for modifying genetic factors? Am J Med Genet A 164A:2161–2171

    Article  PubMed  Google Scholar 

  28. Roberts AB, Campbell S (1980) Small biparietal diameter of fetuses with spina bifida: implications for antenatal screening. Br J Obstet Gynaecol 87:927–928

    Article  PubMed  CAS  Google Scholar 

  29. Schwarzler P, Homfray T, Bernard JP, Bland JM, Ville Y (2003) Late onset microcephaly: failure of prenatal diagnosis. Ultrasound Obstet Gynecol 22:640–642

    Article  PubMed  CAS  Google Scholar 

  30. Shaffer LG, Rosenfeld JA, Dabell MP, Coppinger J, Bandholz AM, Ellison JW, Ravnan JB, Torchia BS, Ballif BC, Fisher AJ (2012) Detection rates of clinically significant genomic alterations by microarray analysis for specific anomalies detected by ultrasound. Prenat Diagn 32:986–995

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Stoler-Poria S, Lev D, Schweiger A, Lerman-Sagie T, Malinger G (2010) Developmental outcome of isolated fetal microcephaly. Ultrasound Obstet Gynecol 36:154–158

    Article  Google Scholar 

  32. Szabo N, Pap C, Kobor J, Svekus A, Turi S, Sztriha L (2010) Primary microcephaly in Hungary: epidemiology and clinical features. Acta Paediatr 99:690–693

  33. Verloes A, Drunat S, Gressens P, Passemard S (1993) Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders. In: Pagon RA, Adam MP, Ardinger HH et al (Hrsg) GeneReviews(R). University of Washington, Seattle

    Google Scholar 

  34. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L (2012) Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med 367:2175–2184

  35. Weisstanner C, Kasprian G, Gruber GM, Brugger PC, Prayer D (2015) MRI, of the Fetal Brain. Clin Neuroradiol. doi:10.1007/s00062-015-0413-z

Download references

Author information

Authors and Affiliations

  1. Praxis für Pränataldiagnostik Berlin-Friedrichstraße, Friedrichstraße 147, 10117, Berlin, Deutschland

    Rabih Chaoui

  2. Zentrum und Institut für Humangenetik, Universität Regensburg, Regensburg, Deutschland

    Ute Hehr

Authors
  1. Rabih Chaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ute Hehr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rabih Chaoui.

Ethics declarations

Interessenkonflikt

R. Chaoui und U. Hehr geben an, dass kein Interessenkonflikt vorliegt.

Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligen Patienten liegt eine Einverständniserklärung vor.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chaoui, R., Hehr, U. Pränataldiagnostik bei fetaler Mikrozephalie. medgen 27, 351–361 (2015). https://doi.org/10.1007/s11825-015-0074-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11825-015-0074-y

Schlüsselwörter

Keywords

Search

Navigation