Session Information
Date: Tuesday, September 24, 2019
Session Title: Classification of Movement Disorders
Session Time: 1:45pm-3:15pm
Location: Les Muses Terrace, Level 3
Objective: To better delineate the genetic landscape and key clinical characteristics that define complex early onset monogenic hyperkinetic movement disorders (HMD).
Background: Hyperkinetic movement disorders (HMD) encompass a broad spectrum of both inherited and acquired conditions that are frequently associated with significant childhood motor disability. Accurate terminology for different hyperkinetic movements in children is essential, not only to facilitate communication between professionals, but also to aid identification of the underlying aetiology, and selection of appropriate medical therapies.
Method: Fourteen internationally-based neuropediatric centres contributed patients with genetic complex childhood-onset HMD. Participating clinicians completed standardised research proformas capturing demographic, clinical and genetic data. Two pediatric movement disorder experts reviewed available video footage and classified hyperkinetic movements according to established criteria.
Results: 143 patients with seventeen genetic defects causing HMDs, both recessive (DDC, DHPR, PTPS, SLC6A3, SPR, TH, MICU1 and PDE10A) and dominant genes (ADCY5, ATP1A3, FOXG1, GCH1, GNAO1, KMT2B, NKX2-1, SGCE, SLC2A1) were identified. In the majority, HMD were generalized (111/143, 78%) with most patients manifesting more than one type of HMD (108/143, 75%). Parkinsonism-dystonia was characteristic of neurotransmitter defects; chorea predominated in ADCY5, ATP1A3, FOXG1, NKX2-1, SLC2A1, GNAO1 and PDE10A-related disorders; stereotypies were prominent in FOXG1 and GNAO1-related disease. Patients with generalized hyperkinesia and developmental delay had a significantly earlier onset than those with focal/segmental distribution (4.7±0.7 vs. 2.4±0.3 years, p=0,001) and normal neurodevelopment ((1.5±2.9 vs 4.7±3.8 years, p<0.001), respectively. Gene-specific effective treatments included dopaminergic agents (neurotransmitters disorders), ketogenic diet (Glut1) flunarizine (ATP1A3) tetrabenazine (GNAO1) and deep brain stimualtion (SGCE, KMT2B and GNAO1-related HMD).
Conclusion: This study delineates the complex movement disorder phenotype and associated features of children with HMD of genetic origin. We propose a pragmatic decision-making algorithm to guide physicians in the rational genetic investigation of patients with suspected genetic HMD, to facilitate prompt diagnosis, precise treatment and future genetic counselling.
To cite this abstract in AMA style:
M. Kurian, V. Leuzzi, K. Peall, R. Pons, R. Dale, E. de Grandis, S. Yilmaz, J. Cobben, R. Guerrini, E. Sheridan, P. Vieira, J. Uusimaa, P. Munot, F. Muntoni, M. Smith, S. Mohammed, E. Meyer, J. Ng, A. Papandreou, H. Baide, F. Danti, A. Macaya, J. Ortigoza, K. Gorman, B. Perez Duenas. The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders [abstract]. Mov Disord. 2019; 34 (suppl 2). https://www.mdsabstracts.org/abstract/the-genetic-landscape-of-complex-childhood-onset-hyperkinetic-movement-disorders/. Accessed June 14, 2025.« Back to 2019 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-genetic-landscape-of-complex-childhood-onset-hyperkinetic-movement-disorders/