Epilepsie und Morbus Darier - erhöht die Dermatose das Epilepsierisiko?

Morbus Darier ist eine autosomal-dominant vererbte Hautkrankheit aufgrund von Mutationen in dem Gen ATP2A2, das für eine Ca2+-ATPase (SERCA2) kodiert. Es kommt zu einer Zerstörung des Zellverbandes sowie zu einer hyperkeratotischen Bildung von Papeln. Bei Patienten mit Morbus Darier wurde das gehäuf...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
1. Verfasser: Nolting, Julia Kathinka
Beteiligte: Klein, Karl Martin (Prof. Dr. Ph.D.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Deutsch
Veröffentlicht: Philipps-Universität Marburg 2019
Schlagworte:
Online-Zugang:PDF-Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!

Darier's disease is an autosomal dominant inherited skin disease due to mutations in the ATP2A2 gene that encodes for a Ca 2+ -ATPase (SERCA2). As a consequence of the mutation there is a destruction of the cell structure and a hyperkeratotic formation of papules. In patients with Darier's disease, the incidence of neuropsychiatric disorders, including epilepsy, has been described to be elevated (Stoffels et al 2014, Gordon-Smith et al., 2010b), which may be related to the ATP2A2 mutation. A systematic epilepsy-specific investigation of patients with Darier's disease and their relatives with regard to the occurrence of possible seizure symptoms has not yet been performed. The aim of this study was to identify families with possible cosegregation of Darier's disease and epilepsy and to subsequently describe the associated epilepsy syndrome. The study aimed at clarifying if there is an accumulation of epilepsy in patients with Darier's disease and their relatives compared to the general population. Patients with known Darier’s disease were recruited in a multi-centre trial design. Included were patients who were registrated at the Departments of Dermatology of the University of Frankfurt, Mainz and Marburg as well as at the Department of Neurology of the University of Marburg. Patients and their close relatives were interviewed on the phone. This interview was oriented on a validated questionnaire for epilepsy [Reutens et al. 1992]. Twelve patients with Darier's disease and twelve close relatives consented to participate in the study and were questioned by telephone. Consequently, twelve family pedigrees with a total of 410 family members were generated. The phenotype of 353 family members was devised by personal or foreign anamnesis. In five families additional relatives suspected to have Darier’s disease were identified (in total 9 family members). None of the 21 probands with Darier’s disease were diagnosed with epilepsy. One of the 21 index patients had a symptomatic seizure after intracerebral haemorrhage. None of the first-degree relatives of the probands with Darier's disease had epilepsy (0/24). No more distantly related family members with epilepsy could be identified. There is no evidence of a significantly higher prevalence of epilepsy in Darier patients despite the very high sensitivity, specificity and reliability in our study design. Possible reasons for the discrepancy in comparison with previous studies are on the one hand the less specific data collection of previous studies, which was based only on medical databases, and on the other hand the erroneous interpretation of the results. Previous studies may have overestimated the risk of epilepsy by choosing the point prevalence in the normal population rather than the cumulative incidence as a comparison parameter. In order to clarify a possible association of epilepsy and Darier’s disease and draw a firm conclusion, a much more complex study design would be required. This cannot be justified on the background of our results and the unexpected negative findings.