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A Diagnostic Approach for Cerebral Palsy in the Genomic Era

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Abstract

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.

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Acknowledgments

The authors would like to thank the patients and their families and the Kennedy Krieger nursing staff and therapists for their ongoing support.

Conflict of interest

The corresponding author is a paid member of the drug monitoring committee for BlueBirdBio, Inc. There are no other conflicts of interest.

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Authors and Affiliations

  1. Department of Pediatrics, Shriners Hospitals for Children – Honolulu, University of Hawaii, Honolulu, HI, USA

    Ryan W. Lee

  2. Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Andrea Poretti

  3. Divisions of Neurogenetics and Neuroscience, Kennedy Krieger Institute, 707 North Broadway Street 500I, Baltimore, MD, 21205, USA

    Julie S. Cohen & Ali Fatemi

  4. Phelps Center for Cerebral Palsy and Neurodevelopmental Medicine, Kennedy Krieger Institute, Baltimore, MD, USA

    Eric Levey, Hilary Gwynn & Alexander H. Hoon

  5. Department of Neurology, Johns Hopkins University, Baltimore, MD, USA

    Michael V. Johnston & Ali Fatemi

  6. The Hugo W. Moser Research Institute, Kennedy Krieger Institute, Johns Hopkins University, Baltimore, MD, USA

    Michael V. Johnston & Ali Fatemi

  7. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Alexander H. Hoon

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  1. Ryan W. Lee
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Correspondence to Ali Fatemi.

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Lee, R.W., Poretti, A., Cohen, J.S. et al. A Diagnostic Approach for Cerebral Palsy in the Genomic Era. Neuromol Med 16, 821–844 (2014). https://doi.org/10.1007/s12017-014-8331-9

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  • DOI: https://doi.org/10.1007/s12017-014-8331-9

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