Linking autism spectrum disorders and parkinsonism: clinical and genetic association
Abstract Background Autism spectrum disorders (ASD) comprise many complex and clinically distinct neurodevelopmental conditions, with increasing evidence linking them to parkinsonism. Methods We searched Medline and Embase from inception to 21 March 2022 and reviewed the bibliographies of relevant a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.51736 |
| _version_ | 1797845245557211136 |
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| author | Aaron Shengting Mai Chun En Yau Fan Shuen Tseng Qi Xuan Joel Foo Dennis Qing Wang Eng‐King Tan |
| author_facet | Aaron Shengting Mai Chun En Yau Fan Shuen Tseng Qi Xuan Joel Foo Dennis Qing Wang Eng‐King Tan |
| author_sort | Aaron Shengting Mai |
| collection | DOAJ |
| description | Abstract Background Autism spectrum disorders (ASD) comprise many complex and clinically distinct neurodevelopmental conditions, with increasing evidence linking them to parkinsonism. Methods We searched Medline and Embase from inception to 21 March 2022 and reviewed the bibliographies of relevant articles. Studies were screened and reviewed comprehensively by two independent authors. Results Of 863 references from our search, we included eight clinical studies, nine genetic studies, and five case reports. Regardless of age group, Parkinson's disease (PD) and parkinsonian syndromes were more frequently observed in patients with ASD, though the evidence for increased rates of parkinsonism is less clear for children and adolescents. Parkinsonian features and hypokinetic behavior were common in Rett syndrome, with prevalence estimates ranging from 40% to 80%. Frequently observed parkinsonian features include bradykinesia, rigidity, hypomimia, and gait freezing. PD gene PARK2 copy number variations appear more frequently in ASD cases than controls. Evidence suggests that RIT2 and CD157/BST1 are implicated in ASD and PD, while the evidence for other PD‐related genes (DRD2, GPCR37, the SLC gene family, and SMPD1) is less clear. Rare mutations, such as ATP13A2, CLN3, and WDR45, could result in autistic behavior and concomitant parkinsonism. Conclusion The prevalence of parkinsonism in ASD is substantially greater than in the general population or matched controls. Various PD‐associated gene loci, especially PARK2, could confer susceptibility to ASD as well. Important future directions include conducting prospective cohort studies to understand how parkinsonian symptoms may progress, genetic studies to reveal relevant gene loci, and pathophysiologic studies to identify potential therapeutic targets. |
| first_indexed | 2024-04-09T17:35:40Z |
| format | Article |
| id | doaj.art-18e2b562fa2c4cb0acfb3e75d21508d3 |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-04-09T17:35:40Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-18e2b562fa2c4cb0acfb3e75d21508d32023-04-17T16:16:03ZengWileyAnnals of Clinical and Translational Neurology2328-95032023-04-0110448449610.1002/acn3.51736Linking autism spectrum disorders and parkinsonism: clinical and genetic associationAaron Shengting Mai0Chun En Yau1Fan Shuen Tseng2Qi Xuan Joel Foo3Dennis Qing Wang4Eng‐King Tan5Yong Loo Lin School of Medicine National University of Singapore Singapore SingaporeYong Loo Lin School of Medicine National University of Singapore Singapore SingaporeDepartment of Neurology, Singapore General Hospital Campus National Neuroscience Institute Singapore SingaporeDepartment of Neurology, Singapore General Hospital Campus National Neuroscience Institute Singapore SingaporeDepartment of Neurology Zhujiang Hospital of Southern Medical University, Southern Medical University Guangzhou ChinaDepartment of Neurology, Singapore General Hospital Campus National Neuroscience Institute Singapore SingaporeAbstract Background Autism spectrum disorders (ASD) comprise many complex and clinically distinct neurodevelopmental conditions, with increasing evidence linking them to parkinsonism. Methods We searched Medline and Embase from inception to 21 March 2022 and reviewed the bibliographies of relevant articles. Studies were screened and reviewed comprehensively by two independent authors. Results Of 863 references from our search, we included eight clinical studies, nine genetic studies, and five case reports. Regardless of age group, Parkinson's disease (PD) and parkinsonian syndromes were more frequently observed in patients with ASD, though the evidence for increased rates of parkinsonism is less clear for children and adolescents. Parkinsonian features and hypokinetic behavior were common in Rett syndrome, with prevalence estimates ranging from 40% to 80%. Frequently observed parkinsonian features include bradykinesia, rigidity, hypomimia, and gait freezing. PD gene PARK2 copy number variations appear more frequently in ASD cases than controls. Evidence suggests that RIT2 and CD157/BST1 are implicated in ASD and PD, while the evidence for other PD‐related genes (DRD2, GPCR37, the SLC gene family, and SMPD1) is less clear. Rare mutations, such as ATP13A2, CLN3, and WDR45, could result in autistic behavior and concomitant parkinsonism. Conclusion The prevalence of parkinsonism in ASD is substantially greater than in the general population or matched controls. Various PD‐associated gene loci, especially PARK2, could confer susceptibility to ASD as well. Important future directions include conducting prospective cohort studies to understand how parkinsonian symptoms may progress, genetic studies to reveal relevant gene loci, and pathophysiologic studies to identify potential therapeutic targets.https://doi.org/10.1002/acn3.51736 |
| spellingShingle | Aaron Shengting Mai Chun En Yau Fan Shuen Tseng Qi Xuan Joel Foo Dennis Qing Wang Eng‐King Tan Linking autism spectrum disorders and parkinsonism: clinical and genetic association Annals of Clinical and Translational Neurology |
| title | Linking autism spectrum disorders and parkinsonism: clinical and genetic association |
| title_full | Linking autism spectrum disorders and parkinsonism: clinical and genetic association |
| title_fullStr | Linking autism spectrum disorders and parkinsonism: clinical and genetic association |
| title_full_unstemmed | Linking autism spectrum disorders and parkinsonism: clinical and genetic association |
| title_short | Linking autism spectrum disorders and parkinsonism: clinical and genetic association |
| title_sort | linking autism spectrum disorders and parkinsonism clinical and genetic association |
| url | https://doi.org/10.1002/acn3.51736 |
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