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Fibrodysplasia ossificans progressiva

Klinische und molekulargenetische Daten von 25 Patienten, Literaturübersicht, Genotyp-Phänotyp-Korrelation

Fibrodysplasia ossificans progressiva

Clinical and molecular genetic data of 25 patients, literature review, and genotype-phenotype correlation

Zusammenfassung

Bei der Fibrodysplasia ossificans progressiva (FOP) handelt es sich um eine sehr seltene, autosomal-dominant vererbbare Erkrankung, die durch Ausbildung von heterotopen Ossifikationen charakterisiert ist, welche zu einer ausgeprägten Mobilitätseinschränkung führen. Angeborene Fehlbildungen von Großzehen im Sinne von Hypoplasie und fibularer Deviation werden bei den meisten Patienten beschrieben. Eine Hypoplasie der Daumen besteht bei etwa der Hälfte der Patienten. Als genetische Ursache der FOP wurden heterozygote Mutationen im ACVR1-Gen identifiziert. Wir berichten über die klinischen und molekulargenetischen Daten von 25 eigenen Patienten (3 bereits veröffentlicht) und weiteren 47 Patienten aus der Literatur mit bekannten Mutationen, bei denen klinische Daten vorlagen und stellen eine Genotyp-Phänotyp-Korrelation dar.

Abstract

Fibrodysplasia ossificans progressiva is a rare autosomal dominant genetic disorder and the most disabling condition of heterotopic ossification in humans. Congenital malformation of the great toes in terms of hypoplasia or aplasia and fibular deviation is noted in almost all patients, and a hypoplasia of the thumbs in about half of the patients. Mutations in the ACVR1 gene were identified as a genetic cause of FOP. We summarize the clinical and molecular data of 25 patients from our cohort as well as of 47 patients with known mutations, and the clinical information described in the literature so far. We discuss these summarized data in terms of genotype-phenotype correlation.

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Danksagung

Wir bedanken uns bei allen Patienten, die an dieser Studie teilgenommen haben, bei ihren Familien sowie beim Förderverein für Fibrodysplasia Ossificans Progressiva-Erkrankte FOP e. V. Weiterhin geht unser Dank an die betreuenden Ärzte für die Zuweisung der Patienten sowie an Prof. Stefan Mundlos und Prof. Frederick Kaplan, die die molekulargenetische Diagnostik im ACVR1-Gen durchgeführt haben.

Interessenkonflikt

Die korrespondierende Autorin gibt für sich und ihre Koautoren an, dass kein Interessenkonflikt besteht.

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Correspondence to I. Stefanova.

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Stefanova, I., Grünberg, C. & Gillessen-Kaesbach, G. Fibrodysplasia ossificans progressiva. medgen 24, 20–32 (2012). https://doi.org/10.1007/s11825-012-0315-2

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Schlüsselwörter

  • Fibrodysplasia ossificans progressiva
  • Ossifikation, heterotope
  • Großzehenfehlbildungen
  • Fibulare Deviation

Keywords

  • Fibrodysplasia ossificans progressiva
  • Ossification, heterotopic
  • Monophalangism of the great toes
  • Fibular deviation