Cerebral palsy in the genomic era

Administrator: Brahim Tabarki Melaiki , Saudi Arabia/Tunisia

Professor Clara van Karnebeek
Radboud University Medical Center, Nijmegen, the Netherlands
clara.vankarnebeek@radboudumc.nl
Atypical cerebral palsy: can we translate big data into better outcomes?
The presentation and etiology of cerebral palsy (CP) are heterogeneous. Diagnostic evaluation can be a prolonged and expensive process that might remain inconclusive. Here we will present on the results of study applying genomic and/or metabolomics analyses in >100 individuals with atypical CP. Previous assessment by a neurologist and/or clinical geneticist, including biochemical testing, neuroimaging, and chromosomal microarray, did not yield an etiologic diagnosis. In more than 50% of cases -omics analyses enabled a molecular diagnosis, ending the diagnostic odyssey, improving genetic counseling, and in a subset allowing a test of targeted intervention. I will discuss the strengths and limitations of big data analyses, its translation into tailored care as well as the potential enhance precision medicine practices.

Professor BRAHIM TABARKI MELAIKI
Prince Sultan Military Medical City, Riyadh, Saudi Arabia and university of Sousse, Tunisia
btabarki@hotmail.com
Metabolic/genetic movement disorders mimicking cerebral palsy
Inherited metabolic/genetic diseases that present with movement disorders are an important and evolving group of disorders. Their clinical presentation can mimic cerebral palsy particularly at early age. These diseases include Segawa disease, neurotransmitters disorders, neurodegeneration with brain iron accumulation, GNAO1-related movement disorders, and many others. Early detection of treatable inborn error of metabolism allows for timely interventions to prevent disease progression and irreversible CNS damage and, in some cases, to improve neurological functioning. Detection of an inherited metabolic/genetic disease for which no treatment currently exists allows for counseling of the affected families, improved management of comorbidities, and provides the essential stepping stone for future research.

Dr Darius Ebrahimi-Fakhari
Department of Neurology, The F.M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
darius.ebrahimi-fakhari@childrens.harvard.edu
Childhood-onset Hereditary Spastic Paraplegia: Update on the Clinical and Molecular Spectrum
The hereditary spastic paraplegias (HSP) are a group of more than 80 neurodegenerative diseases that lead to progressive neurological decline. Collectively the HSPs present the most common cause of inherited spasticity and associated disability in children. Early-onset forms of hereditary spastic paraplegia and inborn errors of metabolism that present with spastic diplegia are among the most common "mimics" of cerebral palsy. Early detection of these heterogenous genetic disorders can inform genetic counseling, anticipatory guidance, and improve outcomes, particularly where specific treatments existIn this lecture, we will be discussing the evolving spectrum of childhood-onset HSP. This will include an overview of the clinical spectrum, including a discussion of HSP as a “mimic of cerebral palsy”. We will review the molecular spectrum and pathways implicated in common forms of HSP. To this end, we will highlight an approach to developing new targeted therapies by the example of SPG47, a complex form of HSP associated with defective protein trafficking.

Dr Wejdan Hakami
Prince Sultan Military Medical City, Riyadh, Saudi Arabia
wejdanhakami@hotmail.com
Precision medicine in pediatric movement disorders
Precision medicine for genetic childhood movement disorders is developing rapidly. Increasingly effective targeted precision medicine is either already available or in development for a number of genetic childhood movement disorders. Patient-centred, personalized approaches include the repurposing of existing treatments for specific conditions and the development of novel therapies that target the underlying genetic defect or disease mechanism. Reduction of accumulating toxic molecules (as in Wilson disease), dietary intervention (as in SLC2A1), target drugs with known mechanisms of action (as in Dopa-responsive dystonia), DBS, gene therapy, and many others. Accurate diagnosis, disease-specific outcome measures, and collaborative multidisciplinary work will accelerate the progress of such strategies.