Genetische Aspekte von Urogenitalfehlbildungen

Zusammenfassung

Urogenitale Malformationen sind häufig. Pränatal werden bereits 30% diagnostiziert. 60–80% der Patienten mit einer chronischen Niereninsuffizienz leiden an einer urogenitalen Malformation. In 5–9% der Fälle sind chromosomale Anomalien zu finden. Isolierte als auch syndromale Hypospadien sind relativ häufig. 30% der Hypospadien weisen monogenetische Ursachen auf, 70% sind als idiopathisch zu betrachten. Vaginale und uterine Fehlbildungen zeigen eine relativ hohe Inzidenz. Die Ursache von einigen syndromalen Formen ist bekannt. Defekte für isolierte Formen sind nicht beschrieben. Für den seltenen, meist spontan und isoliert auftretenden Blasenekstrophie-Epispadie-Komplex ist bislang kein Gendefekt beschrieben. Zur genetischen Evaluation einer urogenitalen Malformation ist vorab ein abgestimmtes Panel aus Anamnese, klinischer Untersuchung, laborchemischer Diagnostik und apparativer Untersuchung wichtig. Es muss auf minimale Stigmata, wie genitale Fehlbildungen, Auffälligkeiten der distalen Extremitäten und andere Dysmorphiezeichen geachtet werden. Je nach Malformation, ist eine interdisziplinäre Abklärung notwendig. Das isolierte oder syndromale bzw. sporadische oder familiär gehäufte Auftreten einer Erkrankung ist für eine genetische Abklärung von Bedeutung. In der Mehrzahl der Fälle findet sich keine kausale Ursache. Bei unklaren Syndromen ist zumindest die Durchführung eines Karyogramms zu empfehlen.

Summary

Urogenital malformations are common. Prenatally 30% can be identified. 60–80% of the patients with chronic renal insufficiency have urogenital malformations. 5–9% show chromosomal anomalies. Isolated and syndromal forms of hypospadias are relatively common. 30% show known monogenetic causes, whereas 70% remain idiopathic. Mullerian duct malformations show a relatively high incidence. No defects are reported for isolated forms, whereas for various syndromic forms genetic defects are known. The rare bladder exstrophy-epispadias complex appears mostly isolated and spontaneously. No gene defects are reported so far. The genetic evaluation of urogenital malformations requires a coordinated work-up comprising patient’s history, clinical examination, laboratory examination, and imaging evaluation. Minimal stigmata as genital malformations, remarkable patterns of the distal limbs as well as other dysmorphic signs have to be recognized. Depending on the pattern of malformations interdisciplinary cooperation is required. In most cases no genetic cause will be identified. Therefore, at least in the case of an unknown syndromic patient a karyogram should be performed.

Schlüsselwörter

Blasenekstrophie-Epispadie-Komplex (BEEK) - Hypospadie - Disorders of Sex Development (DSD) - Uterusfehlbildungen

Keywords

Bladder exstrophy-epispadias complex (BEEK) and Mullerian duct malformations - Hypospadias - Disorders of Sex Development (DSD) - uterine anomalies

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