Zusammenfassung
Das Ausmaß der ursächlichen Wirkung genetischer Faktoren bei der Entstehung von orofazialen Spaltbildungen hängt von der Art der Fehlbildung ab und setzt eine Unterscheidung in vier verschiedene Gruppen voraus. Zum einen muss unterschieden werden zwischen isolierten und syndromalen Spaltbildungen, zum anderen muss differenziert werden zwischen Lippen-Kiefer-Gaumenspalten und Gaumenspalten. Handelt es sich bei der orofazialen Spaltbildung um ein Teilsymptom eines übergeordneten Syndroms, richtet sich die Erblichkeit nach der des Syndroms. Hierbei kann es sich um Chromosomenstörungen, monogene Krankheiten oder auch nicht mendelnde Syndrome handeln. Die isolierte Spaltbildung ist sehr wahrscheinlich multifaktoriell bedingt. Bei multifaktoriell bedingten Erkrankungen führt die kumulative Wirkung von genetischen Varianten an mehreren Genorten zu einer genetischen Prädisposition und bedingt eine „Empfänglichkeit“ für die Entstehung einer Fehlbildung. Es müssen jedoch bestimmte Umwelteinflüsse hinzukommen, so dass das Zusammenwirken von genetischen und umweltbedingten Faktoren zur Entwicklung der Fehlbildung führen kann. Durch Kopplungsanalysen ergaben sich Hinweise auf mehrere Chromosomenregionen, die eine Rolle bei der Entwicklung von orofazialen Spalten spielen könnten. Kandidaten-Gene, von denen ein Teil in diesen chromosomalen Bereichen liegen, sind zur Zeit Gegenstand der Forschung.
Genetical Aspects of Cleft Lip with or without
Cleft Palate and Cleft Palate
The causative role of genetic factors in clefting depends on type of orofacial clefts. They can be divided in non-syndromic and syndromic clefts, and in cleft lip with or without cleft palate and cleft palate only. When the cleft occurs as one component of a multiple congenital anomaly syndrome, the heredity depends on the syndrome's cause. Syndromes have chromosomal, monogenic or non-mendelian origins. Non-syndromic clefts are very likely to be multifactorial. In multifactorial diseases a genetic predisposition reflects the cumulative effect of genetic variation at multiple loci and leads to susceptibility to disease. Environmental triggers must be present to bring out the disease by gene-environmental interactions. Linkage studies found suggestions of several chromosomal loci to play a role in clefting. Candidate genes, some of them mapping to these regions, are currently under investigation.
Schlüsselwörter
Lippen-Kiefer-Gaumenspalte - Gaumenspalte - multifaktoriell - isoliert - syndromal
Key words
Cleft Lip and Palate - Cleft Palate - Multifactorial - Isolated - Syndromic
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Dr. med. Mine Arslan-Kirchner
Institut für Humangenetik
Medizinische Hochschule Hannover
Carl-Neuberg-Straße 1
30625 Hannover
