Neuropediatrics 2012; 43 - PS13_09
DOI: 10.1055/s-0032-1307096

Sleepless flies – Clinical and molecular genetic characterization of sleep disturbances in neurofibromatosis

T Rosenbaum 1, A Wiater 2, V Stahn 3, A Jeibmann 3, A Harder 3
  • 1Klinik für Kinder- u. Jugendmedizin, Klinikum Duisburg, Duisburg, Germany
  • 2Kinderklinik, Krankenhaus Porz am Rhein, Köln, Germany
  • 3Institut für Neuropathologie, Universitätsklinikum Münster, Münster, Germany

Aims: Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene (17q22.1) and is mainly characterized by hyperpigmented macules of the skin (café-au-lait spots) and tumors of the perpheral nervous system (neurofibromas). However, in childhood behavioral problems can dominate the clinical picture. Sleep disturbances can play a key role and become a heavy burden for affected families. In drosophila NF1 mutations result in abnormalities of circadian rhythms. Therefore, we propose that sleep disturbances in children with NF1 might be caused by mutations of the human NF1 gene and are part of the phenotypic spectrum of the disease.

Methods: In the medical part of our project we will identify children with NF1-associated sleep disturbances in our NF clinic, clinically characterize these patients and analyze the sleep disorder following a standardized protocol. We will investigate if NF1-associated sleep disturbances show a characteristic pattern and are connected to abnormalites of circadian rhythms. Furthermore, we will assess the therapeutic effects of melatonin. In the scientific part of our project we will recapitulate the circadian phenotype in the NF animal model drosophila. We will analyze which NF mutants show abnormalities of circadian behavior and if differences between various mutants can be attributed to specific domains involved in the regulation of circadian rhythms. Therapeutic effects of melatonin will be studied in drosophila, too, and we plan to analyze if melatonin affects the cAMP-metabolism in these animals.

Results: This research project will provide a first detailed clinical characterization of NF1-associated sleep disturbances and will generate important data in order to elucidate the molecular basis of these sleep disturbances.

Conclusion: Sleep disturbances are part of the phenotypic spectrum of NF1 and can be described as biochemical processes which are disturbed due to NF1 mutations. Our results can help to develop new therapies for sleep disorders in NF1.

NF1 - sleep disturbances - melatonin - drosophila - circadian rhythm