Neuropediatrics 2019; 50(S 02): S1-S55
DOI: 10.1055/s-0039-1698252
Poster Presentations
Poster Area GNP Neuromuscular Diseases/Varia 2
Georg Thieme Verlag KG Stuttgart · New York

Dyneinopathies - Phenotypic Insights in DYNC1H1 Related Neurodevelopmental Disorders

Authors

  • Jens Schallner

    1   Neuropädiatrie, Dresden, Germany

  • Lena Becker

    2   Charité - Universitätsmedizin Berlin, Departement of Pediatric Neurology, Abteilung Neuropädiatrie, Berlin, Germany

  • Nataliya Di Donato

    3   Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Institut für Klinische Genetik, Dresden, Germany

  • Maja von der Hagen

    4   Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Abteilung Neuropädiatrie, Dresden, Germany
Further Information

Publication History

Publication Date:
11 September 2019 (online)

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Problem: Cytopasmic dynein 1 heavy chain 1 (DYNC1H1; MIM_600112) encodes the heavy chain of cytoplasmic dynein complex 1, a 1.4-MDa motor complex that traffics organelles, vesicles, and macromolecules toward microtubule minus ends. First described in 2010, mutations in DYNC1H1 gene were detected in association with rare neuropathies: spinal muscular atrophy with lower extremity predominant (SMA-LED; OMIM_158600) and axonal Charcot-Marie Tooth Disease (CMT20; OMIM_614228), autosomal dominant intellectual disability with neuronal migration defects (MRD13; OMIM_614563) and malformations of cortical development (MCD). However, the clinical course even in one affected family appears highly variable.

Material and Methods: We report on four children (P1 – P4) with neurodevelopmental disorders associated with novel mutations in the DYNC1H1 gene, affecting not only the peripheral (PNS) but also the central (CNS) nervous system.

Results: All patients can be placed within the group of DYNC1H1-related disorders with CNS involvement and demonstrate the full severity spectrum.

Discussion: Due to rapid advances in next-generation sequencing (NGS) technologies, an increasing number of mutations in DYNC1H1 are identified, associated with an expanding spectrum of rare neurodevelopmental disorders. Accurate genotype–phenotype correlation have been difficult to delineate.

Conclusion: As an orphan disease, DYNC1H1 related disorders are probably underdiagnosed. The four patients reported here, represent the different ends (“PNS” versus “CNS” phenotype) of the clinical spectrum and display a marked disease overlap.


No conflict of interest has been declared by the author(s).