A diagnostic approach for cerebral palsy in the genomic era

Neuromolecular Med. 2014 Dec;16(4):821-44. doi: 10.1007/s12017-014-8331-9. Epub 2014 Oct 4.


An ongoing challenge in children presenting with motor delay/impairment early in life is to identify neurogenetic disorders with a clinical phenotype, which can be misdiagnosed as cerebral palsy (CP). To help distinguish patients in these two groups, conventional magnetic resonance imaging of the brain has been of great benefit in "unmasking" many of these genetic etiologies and has provided important clues to differential diagnosis in others. Recent advances in molecular genetics such as chromosomal microarray and next-generation sequencing have further revolutionized the understanding of etiology by more precisely classifying these disorders with a molecular cause. In this paper, we present a review of neurogenetic disorders masquerading as cerebral palsy evaluated at one institution. We have included representative case examples children presenting with dyskinetic, spastic, and ataxic phenotypes, with the intent to highlight the time-honored approach of using clinical tools of history and examination to focus the subsequent etiologic search with advanced neuroimaging modalities and molecular genetic tools. A precise diagnosis of these masqueraders and their differentiation from CP is important in terms of therapy, prognosis, and family counseling. In summary, this review serves as a continued call to remain vigilant for current and other to-be-discovered neurogenetic masqueraders of cerebral palsy, thereby optimizing care for patients and their families.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Asphyxia Neonatorum / diagnosis
  • Asphyxia Neonatorum / genetics
  • Birth Injuries / diagnosis
  • Birth Injuries / genetics
  • Brain / embryology
  • Brain Diseases, Metabolic / diagnosis
  • Brain Diseases, Metabolic / genetics
  • Cell Movement
  • Cerebral Palsy / diagnosis*
  • Cerebral Palsy / genetics
  • Child
  • Child, Preschool
  • Chromosome Disorders / diagnosis
  • Chromosome Disorders / genetics
  • Developmental Disabilities / diagnosis*
  • Developmental Disabilities / genetics
  • Diagnosis, Differential
  • Diagnostic Errors*
  • Exome
  • Female
  • Genetic Diseases, Inborn / diagnosis*
  • Genetic Diseases, Inborn / genetics
  • Genome-Wide Association Study
  • Genomics
  • Globus Pallidus / pathology
  • Humans
  • Hypoxia, Brain / diagnosis
  • Hypoxia, Brain / genetics
  • Infant, Newborn
  • Leukoencephalopathies / diagnosis
  • Leukoencephalopathies / genetics
  • Leukoencephalopathies / metabolism
  • Lysosomal Storage Diseases, Nervous System / diagnosis
  • Lysosomal Storage Diseases, Nervous System / genetics
  • Male
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / genetics
  • Molecular Diagnostic Techniques*
  • Movement Disorders / diagnosis
  • Movement Disorders / genetics
  • Muscle Spasticity / diagnosis
  • Muscle Spasticity / genetics
  • Nervous System Diseases / diagnosis*
  • Nervous System Diseases / genetics
  • Neurotransmitter Agents / metabolism
  • Stroke / congenital
  • Stroke / diagnosis
  • Tissue Array Analysis


  • Neurotransmitter Agents