Ann Rehabil Med.  2024 Dec;48(6):369-376. 10.5535/arm.240081.

Genetics of Cerebral Palsy: Diagnosis, Differential Diagnosis, and Beyond

• Jang DH
• Kim J
• Schwabe AL
• Lotze TE

• KMID: 2562967
• DOI: http://doi.org/10.5535/arm.240081

Abstract

Cerebral palsy (CP) is the most common motor disability in children, characterized by diverse clinical manifestations and often uncertain etiology, which has spurred increasing interest in genetic diagnostics. This review synthesizes findings from various studies to enhance understanding of CP’s genetic underpinnings. The discussion is structured around five key areas: monogenic causes and copy number variants directly linked to CP, differential genetic disorders including atypical CP and mimics, ambiguous genetic influences, co-occurrence with other neurodevelopmental disorders, and polygenic risk factors. Case studies illustrate the clinical application of these genetic insights, underscoring the complexity of diagnosing CP due to the phenotypic overlap with other conditions and the potential for misdiagnosis. The review highlights the significant role of advanced genetic testing in distinguishing CP from similar neurodevelopmental disorders and assessing cases with unclear clinical presentations. Furthermore, it addresses the ongoing challenges in establishing a consensus on genetic contributors to CP, the need for comprehensive patient phenotyping, and the integration of rigorous genetic and functional studies to validate findings. This comprehensive examination of CP genetics aims to pave the way for more precise diagnostics and personalized treatment plans, urging continued research to overcome the current limitations and refine diagnostic criteria within this field.

Keyword

Cerebral palsy; Genetic testing; Neurodevelopmental disorder; Differential diagnosis

Figure

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  Fig. 1. Axial and coronal T2-weighted brain magnetic resonance images of the patient show periventricular nodular heterotopia (arrows).

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  Fig. 2. Sagittal T1-weighted brain magnetic resonance images of the patient show interval development of atrophy in the cerebellar vermis and hemispheres at ages 1 year (A), 5 years (B), and 7 years (C).

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  Fig. 3. Axial T2-fluid attenuated inversion recovery brain magnetic resonance images of the patient show posthemorrhagic ventricular enlargement.

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