Biomarker Predictors of Rehabilitation Response in Hypotonic Cerebral Palsy: A Scoping Review

Background: Hypotonic cerebral palsy (HCP) represents a clinically distinct and underresearched subtype of cerebral palsy characterized by reduced muscle tone, delayed motor milestones, and highly variable rehabilitation outcomes. Despite growing interest in precision rehabilitation, no systematic synthesis has examined which biomarkers predict individual response to rehabilitation interventions in this population. Objective: This scoping review maps the current evidence on candidate biomarkers—neuroimaging, neurophysiological, genetic, and fluid-based—that may predict or correlate with rehabilitation outcomes in children and adolescents with hypotonic cerebral palsy. Methods: A structured literature search was conducted across PubMed/MEDLINE and Semantic Scholar using Boolean queries combining terms for hypotonic cerebral palsy, muscle tone, biomarkers, and rehabilitation. Studies were screened for relevance to the HCP population and biomarker-outcome relationships. Evidence was synthesized narratively given the heterogeneity of included sources. Results: Evidence directly addressing biomarker predictors in HCP is sparse. Related literature from broader CP populations identifies structural MRI connectivity measures, EEG coherence patterns, BDNF Val66Met polymorphism, and serum BDNF levels as promising candidates. Functional near-infrared spectroscopy and corticospinal tract integrity metrics have shown preliminary associations with motor learning in hypotonic presentations. A critical evidence gap exists: no prospective study has validated a biomarker panel specifically for predicting HCP rehabilitation response. Conclusions: Hypotonic cerebral palsy remains a neglected area within CP biomarker research. This review identifies key candidate biomarkers and frames a research agenda for future prospective cohort studies. Validated predictive biomarkers could enable individualized, evidence-based rehabilitation planning for children with HCP. Correspondence: david.sarlak1@gmail.com