Mar 15, 2019 Unmasking genetic diseases masquerading as cerebral palsy

Genomic analysis reveals rare inherited diseases in patients originally diagnosed with cerebral palsy

Cerebral palsy is one of the most common neurological disorders, yet some cases might be misdiagnosed

© Jaren Jai Wicklund/ Shutterstock

Advances in genetic testing are increasing the evidence that some cases diagnosed as cerebral palsy may actually be genetic diseases. Research in Japan now indicates there may be more genetic diseases posing as cerebral palsy than previously thought.

Cerebral palsy is one of the most common neurological disorders, affecting around 17 million people worldwide. Usually diagnosed in childhood, this disorder impairs the body’s ability to control movement and posture. It often occurs as a result of damage or disruption of blood supply to the developing brain of the foetus during pregnancy.

Magnetic resonance imaging (MRI) is crucial to accurate disease diagnosis. Non-specific findings, such as the ones shown here, can exclude environmental causes and other particular disorders.

Reproduced from reference one under Creative Commons License © 2018 Takezawa et al.

The researchers examined 897 cases of cerebral palsy at the Takuto Rehabilitation Center for Children in Sendai, Japan. Patients were categorised according to two criteria: firstly, they had to be full-term children (born at 37 weeks or more) and secondly, they had to have brain MRI scans that did not show specific findings. The first criteria effectively removed pre-term infants, known to be vulnerable to external factors and therefore at an increased risk of cerebral palsy, while the second criteria excluded environmental causes or other disorders.

From a shortlist of 107 patients, 17 were available for in-depth genetic testing. In 9 out of these 17 cases, the researchers detected causative variants for genetic disorders including hereditary spastic paraplegia and infantile epileptic encephalopathy.

The high proportion of genetic-based disorders in this relatively small subset implies that broader testing is warranted for cerebral palsy patients.

First author of this research Yusuke Takezawa of the Department of Pediatrics, Tohoku University School of Medicine points out that the extent of the problem is still unknown. “For example, the Japan Council for Quality Health Care has reported that around 40 per cent of cerebral palsy cases in Japan are not yet linked to a certain aetiology or cause,” he says. “Some of these cases might have genetic aetiologies. However, we don’t know enough yet about how many and what kind of patients should undergo further genetic investigation. These are still problems to be solved.”

Reflecting on the present study, Takezawa says that genomic analysis techniques, such as trio whole exome sequencing (WES) and array comparative genomic hybridization (aCGH), provided an efficient way of detecting candidate variants, even in genes not yet associated with cerebral palsy. “Thanks to trio WES, we were able to identify more pathogenic variants compared to gene-panel sequencing,” he says.

As a key outcome, Takezawa observes that distinguishing masquerading diseases from cerebral palsy “will expand basic knowledge of genetic diseases and facilitate the development of novel gene therapies.”

The program-affiliated researchers contributing to this research are from the Department of Pediatrics, Tohoku University School of Medicine, Japan.


  1. Takezawa, Y. Atsuo Kikuchi, A., Haginoya, K., Niihori, T., Numata-Uematsu, Y. et al. Genomic analysis identifies masqueraders of full-term cerebral palsy. Annals of Clinical and Translational Neurology 5, 538–551 (2018).| Article

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