2025 American Academy of Neurology Abstract Website

Sue Park¹, Sydney Peters¹, Ryan Carrier², Kristin Falbo⁶, Kristen Sportiello¹, Hayley Schultz¹, Alexander Paciorkowski³, Catherine Nicholas², Melissa A. LoPresti⁴, Shreya Mandalapu⁷, Sarah Mohajeri⁵, Ashlie Nguyen⁶, David Bearden²
¹University of Rochester School of Medicine, ²Child Neurology, ³Neurology, ⁴Neurosurgery, ⁵Imaging Sciences, University of Rochester School of Medicine, ⁶Roberts Wesleyan University, ⁷University of Rochester

Objective:

To characterize the prevalence and clinical presentation of tethered cord (TC) and outcomes of surgical untethering in pediatric patients with ZC4H2-Associated Rare Disorders (ZARD).

Background:

ZARD encompasses various X-linked allelic syndromes caused by variations in the ZC4H2 gene, which encodes a zinc-finger protein critical in spinal cord development. Recent studies suggest a high frequency of TC in children with ZARD, but its prevalence, presentation, and surgical outcomes in this population remain unknown.

Design/Methods:

The ZC4H2-Associated Rare Disorders Natural History Study (ZARD-NHS) is a single-site, non-randomized, longitudinal study involving the prospective evaluation of participants with confirmed ZC4H2 pathogenic variations. Over 24 months, participants are assessed through telemedicine, which includes medical record reviews, caregiver interviews, and standardized virtual physical exams. TC diagnoses were confirmed via MRI, and surgical outcomes were evaluated based on caregiver-reported symptom changes.

Results:

Among 51 participants, 40% (21/51) had confirmed TC diagnoses. 63% of participants (32/51) had a spine MRI and 66% of these participants (21/32) had TC. Prevalence was not statistically different across sex or mutation type. Caregivers of participants with TC were more likely to report spasticity/contractures (p < 0.05), autonomic dysfunction (p < 0.01), gait abnormalities (p < 0.01), GI abnormalities (p < 0.05), generalized muscle weakness (p < 0.05), and urinary retention (p < 0.05). Seventeen participants (81% of those with a TC diagnosis) underwent surgical untethering, with 71% reporting symptomatic improvement after surgery, particularly in urological function, spasticity, and pain.

Conclusions:

This study identified a prevalence of TC in participants with ZARD (40-66%) and highlighted the benefits of surgical untethering. Participants with ZARD and TC were more likely to exhibit spasticity/contractures, urinary retention, generalized muscle weakness, and gait abnormalities than participants without TC. MRI screening of the lumbar spine is essential for TC diagnosis, and neurosurgical consultation for tethered cord release can result in improved outcomes.