Developmental disorders correlates with brain abnormalities in type 1 spinal muscular atrophy

*Correspondence: [e-mail].

Abstract

Beckground? Developmental disorders such as speech delay and autistic spectrum disorder (ASD), and also epilepsy are being reported to be associated with prolonged survival in Spinal Muscular Atrophy (SMA) treated patients. Previous studies have demonstrated central nervous system (CNS) involvement as a potential feature in SMA, a genetic disorder characterized by progressive muscle weakness and atrophy due to degeneration of motor neurons in the spinal cord and brainstem. SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene, leading to reduced levels of the SMN protein, which is essential for the survival and function of motor neurons. However, these findings are still described only in case reports and must be systematically evaluated.

Objective: To report that SMA may present developmental disorders and epilepsy, despite the degree of motor impairment and to provide evidence that both cognitive and motor impairment may be related to brain abnormalities demonstrated by volumetric MRI sequences.

Methods: Among an SMA type 1 cohort of 25 patients aged between one and ten years old, we identified and evaluated five children with signs of developmental disorder or involvement of CNS. They were all previously treated with disease-modifying therapies, and four patients were submitted to volumetric MRI analyzed by Neuroquant software. They were also evaluated by a neuropsychologist.

Results: This small patient cohort included four individuals who received treatment after the onset of symptoms and one pre-symptomatic patient. Neurodevelopmental delays were observed in all five patients with SMA. MRI performed in 4 patients (one family did not consent to the exam) revealed the same pattern of reduction of white matter in frontal lobes on volumetric sequences. In addition, these findings correlated with a lower representation of association fibers on Diffusion Tensor Imaging (DTI), particularly of the superior longitudinal fasciculus.

Conclusion: This study demonstrated that CNS and neurodevelopmental changes may happen in SMA and may be linked to changes in white matter, which has important implications for patient care.

Publication History

Article published online:
12 May 2025