ASD in Children with SMA Type I: Diagnostic Challenges in a Multifactorial Context

As children with spinal muscular atrophy (SMA) type I increasingly benefit from early diagnosis and advanced therapies, new challenges are emerging in understanding their neurodevelopmental and behavioral profiles.

A 2025 cross-sectional study published in Scientific Reports has raised critical questions about neurodevelopmental and mental health profiles in children with SMA type I. Conducted at the Nemo Pediatric Medical Center in Rome, the study evaluated 31 children aged 2 to 10 years, all of whom had received disease-modifying therapies. Researchers assessed the prevalence of autism spectrum disorder (ASD) and other behavioral conditions while examining the suitability of standard diagnostic tools for children with severe motor impairment.

An Elevated ASD Prevalence

Three children—approximately 10 percent of the cohort—were diagnosed with ASD based on DSM-5 criteria, with confirmation from the Childhood Autism Rating Scale (CARS2) and structured neurobehavioral observation. This figure is notably higher than the reported 1.3 percent ASD prevalence in the general pediatric population in Italy.

Additional diagnoses included three cases of oppositional defiant disorder (ODD), one of anxiety disorder, and one of attention deficit and hyperactivity disorder (ADHD). Cognitive assessments indicated a broad distribution, with 51 percent of children scoring in the normal range and 29 percent meeting criteria for intellectual disability.

Notably, no consistent association was observed between the severity of motor impairment and likelihood of neurodevelopmental diagnosis. Children meeting criteria for ASD included both those with profound physical limitations and those with milder or presymptomatic presentations. This suggests that behavioral profiles cannot be attributed solely to physical constraints.

The prevalence of other behavioral conditions remained comparable to or below population averages. ODD was found in ten percent of the cohort, while anxiety and ADHD were each observed in one child, or three percent. These outcomes are notable considering contributing risk factors such as high social vulnerability, frequent hospitalization, and elevated caregiver burden.

Challenges with Standard Diagnostic Tools

The study found limitations in the use of conventional screening instruments. Fourteen children had borderline or abnormal scores on the SDQ prosocial subscale—an area associated with ASD risk—but only three of these were ultimately diagnosed. The SCQ identified six borderline scores, but no child met the threshold for a positive screen.

Meanwhile, 87 percent of parents indicated that at least 80 percent of the items in the Sensory Profile 2 (SP2) were compromised by their child’s motor limitations. Several SCQ items, such as nodding, pointing, or engaging in pretend play, were also noted as physically unfeasible, further complicating interpretation.

Clinical Implications and Future Directions

The findings underscore the need for diagnostic pathways adapted to children with neuromuscular disorders. Tools that rely on gross motor behaviors may inflate false positives or overlook symptoms masked by physical limitations. The authors recommend combining structured observations with selected questionnaires and DSM-5-based evaluations, supported by multidisciplinary clinical judgment.

The elevated rate of ASD observed may reflect multifactorial influences. Hypotheses include central nervous system involvement related to reduced SMN protein expression, early sensory and social deprivation, and cumulative stress within the family environment. Further research, including longitudinal and genomic studies, is needed to clarify these associations and develop better-suited diagnostic frameworks.

As children with SMA live longer and acquire previously unobserved developmental milestones, clinicians may reconsider how behavioral and neurodevelopmental symptoms are identified and interpreted. This study provides early evidence that comprehensive, tailored assessments are essential to avoid diagnostic errors and to guide timely support strategies for children and their families.

Reference

Buchignani B, Coratti G, Cutrì C, et al. Neurodevelopmental and mental disorders in children with type I and presymptomatic spinal muscular atrophy. Sci Rep. 2025;15(1):26984. Published 2025 Jul 24.