Unilaterale pulmonale Agenesie, Aplasie und Dysplasie

Zusammenfassung

Unilaterale pulmonale Fehlbildungen sind seltene, ätiologisch ungeklärte Ereignisse mit grosser klinischer Variabilität. Neonatale Symptomatik und Diagnostik lassen keine sichere Prognose zu. Das interdisziplinäre Management schließt Pränataldiagnostik und Geburtshilfe, Humangenetik, Neonatologie, Kinderkardiologie, Kinderchirurgie und – Orthopädie ein. Wir beschreiben die neonatale Symptomatik und den Langzeitverlauf bei drei Patienten, Pränataldiagnostik sowie embryologisch-genetische Grundlagen. Bei drei Patienten wurde die Diagnose einseitige pulmonale Agenesie, Aplasie bzw. Dysplasie mithilfe der Angiografie, MRT und Bronchoskopie in der Neonatalperiode gestellt. Verlauf in der Neonatalperiode und Langzeit-follow-up werden vor dem Hintergrund einer Literaturübersicht dargestellt. Die akute klinische Symptomatik reichte von milder Dyspnoe bis zur schweren pulmnonalen Insuffizienz, in einem Fall entwickelte sich eine Skoliose. Eine kardiale Insuffizienz oder pulmonale Hyertonie zeigte sich bei keinem Patienten. In einem Fall fand sich eine VACTER-Assoziation. Unilaterale Lungenfehlbildungen sind häufig mit anderen, singulären und komplexen Fehlbildungen (v. a. renale und vaskuläre) assoziiert. Ein Zusammenhang mit Störungen der Regulation der an der – asymmetrischen – embryonalen Lungenentwicklung beteiligten T-box-Genen, dem Homöobox-Gen Pitx2 bzw. Wachstumsfaktoren (FGF10) wird diskutiert. Unilaterale pulmonale Fehlbildungen könnten damit Modellcharakter haben für die embryonale Differenzierung der Lungenanlagen und die Ätiologie anderer, einseitiger Lungenfehlbildungen. Pränatal ist die einseitige Hyperchogenität des Lungenparenchyms der entscheidende Hinweis, die akute Symptomatik wird vom Ausmass einer Mediastinalverlagerung bestimmt, welche die Implantation eines Expanders erfordern kann. Assoziierte Fehlbildungen sollten Anlass für Karyotypisierung bzw. Sequenzierung bekannter Mutationen sein. Im Langzeitverlauf sind Echokardiografie, Lungenfunktionsdiagnostik und kinder-orthopädische Verlaufskontrollen unverzichtbar.

Abstract

Unilateral pulmonary anomalies are rare events of unknown etiology and large clinical variability. Neonatal history does not allow for a reliable prognosis. Interdisciplinary mangament includes prenatal diagnostics and obstetrics, genetics, neonatology, pediatric cardiology and surgery as well as pediatric orthopedics. Neonatal history and long-term follow-up in three patients are presented here including a discussion of prenatal diagnostics and the embryo-genetic basics of lung development. In three term neonates the diagnoses of unilateral pulmonary agenesis, aplasia and dysplasia, respectively, were based on angiography, MRI and bronchoscopy. Neonatal presentation and long-term consequences were studied in the context of the current literature. Neonatal complications ranged from mild repiratory distress to pulmonary failure requiring mechanical ventilation. One patient developed scoliosis on long-term follow-up. Cardiac failure or pulmonary hypertension did not occur during follow-up, in one case lung malformation was accompanied by VACTER-association. Unilateral lung malformation is frequently associated with other, singular or complex anomalies (e.g., renal and vascular). A possible relationship to disrupted regulation of embryo-genetic factors such as T-box genes, Pitx2 and growth factors (FGF10), which regulate asymmetrical pulmonary morphogenesis is discussed. Disruptive unilateral pulmonary malformations may serve as a model for embryological lung development and other anomalies (e.g., congenital diaphragmatic hernia, unilateral hypoplasia and CCAM). Prenatal diagnosis is characterized by unilateral hyperechogenicity of the affected lung. Neonatal presentation is determined by mediastinal shift which may be corrected by tissue-expander implantation. Associated anomalies require cytogenetic analysis and sequencing of currently known mutations. Long-term follow-up by echocardiography and pulmonary function testing is mandatory in these patients.

Schlüsselwörter

pulmonale Fehlbildungen - Embryologie - T-box-Gene - Pitx2 - FGF 10

Key words

lung malformation - embryology - T-box genes - Pitx2 - FGF 10

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