Virginia Research Day 2025

Medical Student Research Case Reports

19 Hypertonia in a Child with Down Syndrome and X-Linked Adrenoleukodystrophy

Jason Canestrino, OMS-III; Ralph D. Brown Jr, MD Corresponding author: jcanestrino@vt.vcom.edu

Edward Via College of Osteopathic Medicine - Virginia Campus Carilion Clinic

Down Syndrome (DS) is the most common chromosomal abnormality in humans, characterized by hypotonia due to underdevelopment of the cerebellum. X-linked Adrenoleukodystrophy (ALD) is a rare genetic disorder resulting in the accumulation of very long chain fatty acids in the brain, causing demyelination and hypertonia. The likelihood of a patient having both conditions simultaneously is estimated to range from 1 in 14 million to 35 million. An 8-year-old male with DS and ALD presents to rehabilitation medicine for routine botulinum toxin A (Botox) injections to treat gastrocnemius, soleus, and masseter spasticity. He exhibits knee hyperextension, bilateral leg spasticity, and minor leg scissoring. He is also being treated with diazepam, bilateral ankle-foot orthosis bracing using the Optimal Segmental Kinematics and Alignment method, and umbilical cord stem cell therapy for ALD. These interventions have improved his ability to walk with a flat foot and reduced muscle spasticity. With both

conditions having opposite effects on muscle tone, it is currently unknown why the child presents with only hypertonic signs. Three contributing factors have been hypothesized: (1) ALD-induced demyelination disrupts normal signaling in the motor cortex and cerebellum, leading to increased excitatory signaling and hypertonia; (2) the progressive nature of ALD may overshadow the hypotonia associated with DS; (3) combined cerebellar damage from both conditions could exacerbate compensatory hypertonia as the brain attempts to stabilize posture. Despite the exceptional rarity of this patient presentation, treatment with Botox injections, bracing, physical therapy, and medications has shown to improve functional outcomes. Further research is needed to explore the pathophysiology of muscle tone regulation in children with DS and its unique interactions with other neuromuscular disorders.

Figure 1. Pathophysiology of X-linked Adrenoleukodystrophy. There is a mutation of ABCD1 gene, causing decreased transport of very long chain fatty acids (VLCFA) into the peroxisome through ALDP protein. VLCFA accumulate causing cell death (Modified from Jia et al. 2019).

Figure 2 . Neuron Demyelination in the Central Nervous System. In the brain, oligodendrocytes myelinate neurons which increase speed and efficiency of signaling. When myelin is destroyed, there is a loss of inhibitory signals, and the neuron becomes hyperexcited (green arrow) leading to increased muscle tone (Modified from Bisnis 2022).

111 2025 Research Recognition Day