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Boucher-Neuhäuser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature

Tarnutzer, A. ; Gerth-Kahlert, C. ; Timmann, D. ; Chang, D. ; Harmuth, F. ; Bauer, P. ; Straumann, D. ; Synofzik, M.

In: Journal of Neurology, 2015, vol. 262, no. 1, p. 194-202

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    Titel
    • Boucher-Neuhäuser syndrome: cerebellar degeneration, chorioretinal dystrophy and hypogonadotropic hypogonadism: two novel cases and a review of 40 cases from the literature
    Autor
    • Tarnutzer, A.. Department of Neurology, University Hospital Zurich, Frauenklinikstr. 26, 8091, Zurich, Switzerland
    • Gerth-Kahlert, C.. Department of Ophthalmology, University Hospital Zurich, Zurich, Switzerland
    • Timmann, D.. Department of Neurology, University of Duisburg-Essen, Essen, Germany
    • Chang, D.. Department of Neurology, University of Duisburg-Essen, Essen, Germany
    • Harmuth, F.. Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
    • Bauer, P.. Institute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen, Germany
    • Straumann, D.. Department of Neurology, University Hospital Zurich, Frauenklinikstr. 26, 8091, Zurich, Switzerland
    • Synofzik, M.. Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Journal of Neurology, 2015, vol. 262, no. 1, p. 194-202. Springer Berlin Heidelberg
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:332500
    Summary
    The combination of progressive cerebellar degeneration, hypogonadotropic hypogonadism and chorioretinal dystrophy defines the rare Boucher-Neuhäuser syndrome (BNS), which has recently been linked to autosomal-recessive mutations in the PNPLA6 gene in four index patients. Here we present two novel unrelated patients with BNS, where we identified four recessive PNPLA6 mutations (3 of them novel) as the genetic cause, using a targeted high-throughput approach. This finding provides the first replication from independent families that BNS is caused by PNPLA6 and, moreover, highlights PNPLA6 as the major gene leading to BNS. Given the fact that the major gene causing BNS has thus now been identified, we summarize the spectrum of clinical presentations and phenotype evolution of BNS based on a systematic in-depth review of the literature of previously published cases (n=40). Both the two cases presented here and our review of the literature propose that the clinical presentation of BNS can be variable regarding both the age (ranging from 1 to 40years) and the clinical symptoms at onset (cerebellar ataxia in 38%; vision loss in 36%; delayed puberty in 26%). A substantial fraction of BNS cases may present with relatively selective atrophy of the superior and dorsal parts of the cerebellar vermis along with atrophy of the cerebellar hemispheres on MRI, while brainstem or cortical changes on MRI seem to be present only in small fractions. Also in the literature, no other major genetic causes of BNS other than PNPLA6 mutations were identified.