Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification

Vicente Martinez Cardenas

doi:doi:10.11648/j.frontiers.20250504.11

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Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification

Vicente Martinez Cardenas^*

Published in Frontiers (Volume 5, Issue 4)

Received: 2 October 2025 Accepted: 13 October 2025 Published: 30 October 2025

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Abstract

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by substantial phenotypic and genetic heterogeneity. The recent application of person-centered computational models has allowed the identification of novel clinical subtypes with distinct genetic underpinnings. Objective: To review recent literature on the classification of ASD subtypes through integrative approaches combining clinical, phenotypic, and genomic data, with emphasis on diagnostic, prognostic, and therapeutic implications. Methods: A narrative review of articles published between 2018 and 2024 was conducted in PubMed, Scopus, and Web of Science, using search terms such as “autism subtypes,” “phenotypic clustering,” “genetic architecture in ASD,” and “precision medicine in autism.” Eligible studies included original research, systematic reviews, and meta-analyses. Results: Recent studies have identified at least four robust clinical-biological ASD subtypes using finite mixture modeling and person-centered analyses: (1) social and behavioral challenges, (2) mixed ASD with developmental delay, (3) moderate challenges, and (4) broadly affected subtype. Each group presents distinctive patterns in symptoms, comorbidities, developmental trajectories, and genetic architecture. Both de novo mutations and inherited variants play key roles in molecular differentiation among subtypes. Conclusions: The identification of more homogeneous subgroups within the autism spectrum represents a crucial step toward personalized medicine in ASD. Emerging clinical tools derived from these classifications may enhance prognosis prediction and guide tailored interventions.

Published in	Frontiers (Volume 5, Issue 4)
DOI	10.11648/j.frontiers.20250504.11
Page(s)	159-165
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Autism Spectrum Disorder, Clinical Subtypes, Phenotypic Clustering, Genetic Variants, Personalized Medicine

References

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Cardenas, V. M. (2025). Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification. Frontiers, 5(4), 159-165. https://doi.org/10.11648/j.frontiers.20250504.11

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ACS Style

Cardenas, V. M. Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification. Frontiers. 2025, 5(4), 159-165. doi: 10.11648/j.frontiers.20250504.11

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AMA Style

Cardenas VM. Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification. Frontiers. 2025;5(4):159-165. doi: 10.11648/j.frontiers.20250504.11

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@article{10.11648/j.frontiers.20250504.11,
  author = {Vicente Martinez Cardenas},
  title = {Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification
},
  journal = {Frontiers},
  volume = {5},
  number = {4},
  pages = {159-165},
  doi = {10.11648/j.frontiers.20250504.11},
  url = {https://doi.org/10.11648/j.frontiers.20250504.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.frontiers.20250504.11},
  abstract = {Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by substantial phenotypic and genetic heterogeneity. The recent application of person-centered computational models has allowed the identification of novel clinical subtypes with distinct genetic underpinnings. Objective: To review recent literature on the classification of ASD subtypes through integrative approaches combining clinical, phenotypic, and genomic data, with emphasis on diagnostic, prognostic, and therapeutic implications. Methods: A narrative review of articles published between 2018 and 2024 was conducted in PubMed, Scopus, and Web of Science, using search terms such as “autism subtypes,” “phenotypic clustering,” “genetic architecture in ASD,” and “precision medicine in autism.” Eligible studies included original research, systematic reviews, and meta-analyses. Results: Recent studies have identified at least four robust clinical-biological ASD subtypes using finite mixture modeling and person-centered analyses: (1) social and behavioral challenges, (2) mixed ASD with developmental delay, (3) moderate challenges, and (4) broadly affected subtype. Each group presents distinctive patterns in symptoms, comorbidities, developmental trajectories, and genetic architecture. Both de novo mutations and inherited variants play key roles in molecular differentiation among subtypes. Conclusions: The identification of more homogeneous subgroups within the autism spectrum represents a crucial step toward personalized medicine in ASD. Emerging clinical tools derived from these classifications may enhance prognosis prediction and guide tailored interventions.
},
 year = {2025}
}

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TY  - JOUR
T1  - Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification

AU  - Vicente Martinez Cardenas
Y1  - 2025/10/30
PY  - 2025
N1  - https://doi.org/10.11648/j.frontiers.20250504.11
DO  - 10.11648/j.frontiers.20250504.11
T2  - Frontiers
JF  - Frontiers
JO  - Frontiers
SP  - 159
EP  - 165
PB  - Science Publishing Group
SN  - 2994-7197
UR  - https://doi.org/10.11648/j.frontiers.20250504.11
AB  - Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by substantial phenotypic and genetic heterogeneity. The recent application of person-centered computational models has allowed the identification of novel clinical subtypes with distinct genetic underpinnings. Objective: To review recent literature on the classification of ASD subtypes through integrative approaches combining clinical, phenotypic, and genomic data, with emphasis on diagnostic, prognostic, and therapeutic implications. Methods: A narrative review of articles published between 2018 and 2024 was conducted in PubMed, Scopus, and Web of Science, using search terms such as “autism subtypes,” “phenotypic clustering,” “genetic architecture in ASD,” and “precision medicine in autism.” Eligible studies included original research, systematic reviews, and meta-analyses. Results: Recent studies have identified at least four robust clinical-biological ASD subtypes using finite mixture modeling and person-centered analyses: (1) social and behavioral challenges, (2) mixed ASD with developmental delay, (3) moderate challenges, and (4) broadly affected subtype. Each group presents distinctive patterns in symptoms, comorbidities, developmental trajectories, and genetic architecture. Both de novo mutations and inherited variants play key roles in molecular differentiation among subtypes. Conclusions: The identification of more homogeneous subgroups within the autism spectrum represents a crucial step toward personalized medicine in ASD. Emerging clinical tools derived from these classifications may enhance prognosis prediction and guide tailored interventions.

VL  - 5
IS  - 4
ER  -

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Author Information

Vicente Martinez Cardenas

Department of Pediatrics, Lake City Medical Center, Lake City, the United States

Contact Email

http://orcid.org/0000-0002-6273-2501

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APA Style

Cardenas, V. M. (2025). Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification. Frontiers, 5(4), 159-165. https://doi.org/10.11648/j.frontiers.20250504.11

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ACS Style

Cardenas, V. M. Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification. Frontiers. 2025, 5(4), 159-165. doi: 10.11648/j.frontiers.20250504.11

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AMA Style

Cardenas VM. Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification. Frontiers. 2025;5(4):159-165. doi: 10.11648/j.frontiers.20250504.11

Copy | Download

@article{10.11648/j.frontiers.20250504.11,
  author = {Vicente Martinez Cardenas},
  title = {Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification
},
  journal = {Frontiers},
  volume = {5},
  number = {4},
  pages = {159-165},
  doi = {10.11648/j.frontiers.20250504.11},
  url = {https://doi.org/10.11648/j.frontiers.20250504.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.frontiers.20250504.11},
  abstract = {Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by substantial phenotypic and genetic heterogeneity. The recent application of person-centered computational models has allowed the identification of novel clinical subtypes with distinct genetic underpinnings. Objective: To review recent literature on the classification of ASD subtypes through integrative approaches combining clinical, phenotypic, and genomic data, with emphasis on diagnostic, prognostic, and therapeutic implications. Methods: A narrative review of articles published between 2018 and 2024 was conducted in PubMed, Scopus, and Web of Science, using search terms such as “autism subtypes,” “phenotypic clustering,” “genetic architecture in ASD,” and “precision medicine in autism.” Eligible studies included original research, systematic reviews, and meta-analyses. Results: Recent studies have identified at least four robust clinical-biological ASD subtypes using finite mixture modeling and person-centered analyses: (1) social and behavioral challenges, (2) mixed ASD with developmental delay, (3) moderate challenges, and (4) broadly affected subtype. Each group presents distinctive patterns in symptoms, comorbidities, developmental trajectories, and genetic architecture. Both de novo mutations and inherited variants play key roles in molecular differentiation among subtypes. Conclusions: The identification of more homogeneous subgroups within the autism spectrum represents a crucial step toward personalized medicine in ASD. Emerging clinical tools derived from these classifications may enhance prognosis prediction and guide tailored interventions.
},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Biological and Clinical Subtypes in Autism Spectrum Disorder: A Review of Recent Advances in Phenotypic and Genetic Classification

AU  - Vicente Martinez Cardenas
Y1  - 2025/10/30
PY  - 2025
N1  - https://doi.org/10.11648/j.frontiers.20250504.11
DO  - 10.11648/j.frontiers.20250504.11
T2  - Frontiers
JF  - Frontiers
JO  - Frontiers
SP  - 159
EP  - 165
PB  - Science Publishing Group
SN  - 2994-7197
UR  - https://doi.org/10.11648/j.frontiers.20250504.11
AB  - Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by substantial phenotypic and genetic heterogeneity. The recent application of person-centered computational models has allowed the identification of novel clinical subtypes with distinct genetic underpinnings. Objective: To review recent literature on the classification of ASD subtypes through integrative approaches combining clinical, phenotypic, and genomic data, with emphasis on diagnostic, prognostic, and therapeutic implications. Methods: A narrative review of articles published between 2018 and 2024 was conducted in PubMed, Scopus, and Web of Science, using search terms such as “autism subtypes,” “phenotypic clustering,” “genetic architecture in ASD,” and “precision medicine in autism.” Eligible studies included original research, systematic reviews, and meta-analyses. Results: Recent studies have identified at least four robust clinical-biological ASD subtypes using finite mixture modeling and person-centered analyses: (1) social and behavioral challenges, (2) mixed ASD with developmental delay, (3) moderate challenges, and (4) broadly affected subtype. Each group presents distinctive patterns in symptoms, comorbidities, developmental trajectories, and genetic architecture. Both de novo mutations and inherited variants play key roles in molecular differentiation among subtypes. Conclusions: The identification of more homogeneous subgroups within the autism spectrum represents a crucial step toward personalized medicine in ASD. Emerging clinical tools derived from these classifications may enhance prognosis prediction and guide tailored interventions.

VL  - 5
IS  - 4
ER  -

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