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DOI: 10.1055/s-0038-1628985
Der Tuberöse-Sklerose-Komplex
Tuberous sclerosis complexPublication History
Eingegangen am:
09 April 2010
angenommen am:
28 April 2010
Publication Date:
29 January 2018 (online)
Zusammenfassung
Die tuberöse Sklerose (TS; Synonyme: tuberöse Hirnsklerose, Morbus Bourneville-Pringle, Tuberöse-Sklerose-Komplex [TSC]) ist nach der Neurofibromatose Typ 1 die zweithäufigste Form der Phakomatosen, wobei sie seltener diagnostiziert wird als die Inzidenz vermuten lässt (hohe Dunkelziffer). Während die Penetranz dieser neuroektodermalen Dysplasie bei Mutationen im TSC1- oder TSC2-Gen nahezu vollständig ist, variiert die Expressivität von Merkmalen stark und folgt keiner strikten Genotyp-Phänotyp-Korrelation. Das breite Spektrum klinischer Manifestationen stellt in Hinblick auf Diagnostik und Therapie eine inter-disziplinäre Herausforderung dar. Um eine frühzeitige, evidenzbasierte Betreuung und Therapie durchzuführen, sollten lange Latenzzeiten zwischen Erstmanifestation und einer definitiven klinischen und/oder humangenetischen Diagnose vermieden werden. Dazu dienen die revidierten diagnostischen Major- und Minorkriterien der Tuberous Sclerosis Complex Consensus Conference, auf deren Grundlage die Diagnose einer TS gestellt wird. Typische kutane Manifestationen sind kutane hypomelanotische Makulae, faziale Angiofibrome oder fibröse Plaques, Chagrin-Lederflecken und Koenen-Tumoren. Im ZNS sind es kortikale und subkortikale Tubera, radiale Migrationslinien der Substantia alba, subependymale Noduli und Riesenzellastrozytome, neurologisch funktionelle Krampfanfälle, neuropsychologisch kognitive Dysfunktion, Gedächtnisstörungen, Aufmerksamkeitsdefizite, Verhaltensauffälligkeiten, Lernschwierigkeiten und autistische Störungen. Weitere Organmanifestationen sind renale Angiomyolipome sowie Nierenzysten, kardiale Rhabdomyome, die pulmonale Lymphangioleiomyomatose sowie retinale Hamartome. Seltener diagnostizierte Merkmale sind extrarenale Hamartome von Leber, Milz, Darm und Zunge oder Café-au-laitFlecken und Strabismus. Einzelne Manifestationen sind nicht beweisend für eine TS, sie können jedoch eine oligosymptomatische Verlaufs-form (Minorform) der TS anzeigen. Bei Verdacht auf eine TS gibt die Tuberous Sclerosis Alliance Leitlinien zu Diagnostik, Verlaufskontrolle und Screening. Dabei werden einige Manifestationen wie extrarenale Hamartome nicht berücksichtigt, obwohl diesen eine diagnostische Relevanz zukommt. Neben der klinischen Diagnostik post partum besteht im Einzelfall die Möglichkeit einer pränatalen Diagnostik mittels Sonografie, MRT oder genetischer Pränataldiagnostik. Die Therapie der tuberösen Skle-rose ist bislang symptomatisch, in Form von pharmakologischer und chirurgischer antikonvulsiver Therapie sowie frühzeitiger Erkennung und Verhütung von Komplikationen. Neuerdings gibt es Erfolg versprechende Ansätze für eine kausale Pharmakotherapie der TS.
Summary
Secondary to neurofibromatosis type 1 tuberous sclerosis complex (TSC; tuberous sclerosis, Bourneville-Pringle disease) is the most common phakomatosis. TSC is less often diagnosed than the incidence indicates. Penetrance of the autosomal-dominant multisystem neurocutaneous disorder is almost complete, but expressivity varies widely and studies failed to show a strict genotype-phenotype correlation. The diagnosis, clinical follow-up and therapy of the widespread manifestations are an interdisciplinary challenge. It is important to prevent a long latency period between first manifestations and a definitive clinical or genetic diagnosis. The diagnosis of TSC is based on the revised clinical diagnostic criteria of the Tuberous Sclerosis Complex Consensus Conference. Typical manifestations of skin are hypomelanotic macules, facial angiofibromas, shagreen patches and ungual fibromas. Classic criteria of the central nervous system are cortical or subcortical tubers, white-matter radial migration lines, subependymal nodules or giant cell astrocytomas. Neurological complications are seizures, cognitive dysfunction, impairment of memory, attention, learning and behaviour up to autistic spectrum disorders. Other organs are involved with renal angiomyolipomas and cysts, cardiac rhabdomyomas, pulmonary lymphangiomatosis and retinal hamartomas. Atypical manifestations are extrarenal hamartomas of liver, spleen, gut and tongue, café-au-lait spots and strabism. Isolated organ manifestations are not pathognomic, but can indicate a minor variant. The Tuberous Sclerosis Alliance provides guidelines for diagnostic and surveillance screening in TSC of affected individuals and their families. Apart from the clinical diagnosis, TSC can be diagnosed prenatally by ultrasonography or genetic screening. Therapy of TSC is symptomatically with priority of pharmacological or surgical seizure control and early recognition and prevention of complications. Recently promising results of a causal therapy of TSC were reported.
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