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Klinik und Genetik syndromaler und nichtsyndromaler Kraniosynostosen

Clinical course and genetics of syndromic and non-syndromic craniosynostosis

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medizinische genetik

Zusammenfassung

Kraniosynostosen gehören mit einer Inzidenz von 1:2000 bis 1:3000 Geburten zu den häufigsten kraniofazialen Anomalien. Die durch die vorzeitige Verknöcherung einer oder mehrerer Schädelnähte verursachte Wachstumshemmung kann zu schweren Deformitäten des Schädel- und Gesichtsskeletts führen. Dies sorgt nicht nur für eine große ästhetische Beeinträchtigung, sondern hat auch funktionelle Auswirkungen für die Patienten. Hierzu können u. a. gehören: intrakranielle Drucksteigerung, Atrophie des N. opticus, Atem-, Hör- und Entwicklungsstörungen. Trotz großer Anstrengungen konnten bisher nur für einen Teil der autosomal-dominanten syndromalen Kraniosynostosen die ursächlichen Gene, z. B „fibroblast growth factor receptor 1-3“ (FGFR1-3), „twist basic helix-loop-helix transcription factor 1“ (TWIST1) etc., gefunden werden. Die Ätiologie der nichtsyndromalen Kraniosynostosen bleibt weiterhin ungeklärt. Aufgrund der verbreiteten Anwendung neuer Sequenziertechnologien zur Identifizierung neuer kausaler Gene bei Patienten mit Kraniosynostose kann in den nächsten Jahren mit der Entschlüsselung vieler weiterer krankheitsverursachender Gene gerechnet werden. Insbesondere die syndromalen Formen der Kraniosynostose bedürfen aufgrund ihrer klinischen Komplexität einer interdisziplinären Betreuung. Die einzige Therapieoption besteht derzeit in der kraniofazialen Chirurgie, welche aber die genetisch determinierten pathologischen Wachstumsmuster der komplexen syndromalen Kraniosynostosen langfristig oft nicht beheben kann.

Abstract

With an incidence of 1:2000–1:3000 births, craniosynostoses are among the most common craniofacial anomalies. Growth inhibition caused by premature fusion of one or more cranial sutures can lead to severe deformities of the skull and facial skeleton. Besides the severe aesthetic problems for the patient, it also has important clinical consequences. These may include raised intracranial pressure, optic nerve atrophy, respiratory, and developmental disorders. Despite major efforts, causative genes (e.g., FGFR1-3, TWIST1) have been detected for only a portion of the autosomal dominantly inherited craniosynostosis syndromes. The etiology of non-syndromic craniosynostosis still remains unclear. The application of next generation sequencing technologies will probably lead to the identification of additional causative genes underlying at the least syndromic forms of craniosynostosis in upcoming years. Due to their clinical complexity, particularly the syndromic forms of craniosynostosis require interdisciplinary care. The only treatment option currently available is craniofacial surgery, which in the long term often fails to remedy the genetically determined pathological growth pattern of complex syndromic craniosynostoses.

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Danksagung

Die Autoren danken Karin Boss für ihre kritischen Ergänzungen beim Schreiben dieses Artikels.

Einhaltung ethischer Richtlinien

Interessenkonflikt. B. Wollnik wird durch die BMBF-geförderten Netzwerke für seltene Erkrankungen CRANIRARE-2 (E-RARE-Programm) mit dem Förderkennzeichen 01GM1211A und FACE (Forschungsverbund ausgewählter craniofacialer Entwicklungsstörungen) mit dem Förderkennzeichen 01GM1109C unterstützt. M. Rachwalski und W. Kress geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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  1. Institut für Humangenetik, Uniklinik Köln, Kerpener Str. 34, 50931, Köln, Deutschland

    M. Rachwalski &  B. Wollnik

  2. Institut für Humangenetik, Universität Würzburg, Würzburg, Deutschland

    W. Kress

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  1. M. Rachwalski
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Correspondence to B. Wollnik.

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Rachwalski, M., Wollnik, B. & Kress, W. Klinik und Genetik syndromaler und nichtsyndromaler Kraniosynostosen. medgen 25, 373–387 (2013). https://doi.org/10.1007/s11825-013-0412-x

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