Spinal Involvement in Charge Syndrome: Implications for Management

CHARGE syndrome (OMIM #214800) is an autosomal dominant disorder caused by mutations in the CHD7 gene in most cases. Although originally defined by the CHARGE acronym (coloboma, heart defects, choanal atresia, growth restriction, genital hypoplasia, and ear anomalies), the recognized phenotype has expanded considerably to include highly prevalent manifestations such as cranial nerve dysfunction, vestibular anomalies, feeding and gastrointestinal complications, endocrine abnormalities, and musculoskeletal involvement. Skeletal abnormalities have been described previously; however, the frequency, spectrum, and clinical significance of spinal abnormalities remain incompletely characterized and are likely underrecognized. We conducted a retrospective review of 54 individuals with CHARGE syndrome to characterize spinal involvement and evaluate implications for management. Skeletal imaging was available in 40 of the 54, among whom abnormalities demonstrated considerable phenotypic heterogeneity, highlighting the importance of systematic musculoskeletal evaluation. Skeletal abnormalities were identified in 70% of individuals and included vertebral segmentation defects, intervertebral disc space narrowing, rib anomalies, and scoliosis. Scoliosis or kyphosis of any degree was present in 60% of the imaged individuals. Cervical spine involvement was identified in 43%. Two individuals (4%) were found to have os odontoideum, one of whom developed clinically significant atlantoaxial instability requiring surgical stabilization. Osteopenia was identified in 33% of individuals. Our findings further support previous reports demonstrating that spinal abnormalities are common in CHARGE syndrome while identifying os odontoideum as a previously unrecognized cervical spine manifestation with important clinical implications. Given that neuroimaging is frequently performed in CHARGE syndrome for evaluation of inner ear and cranial nerve abnormalities, careful assessment of the cervical spine during these studies may facilitate early recognition of clinically significant abnormalities without substantially increasing imaging burden. Our findings also emphasize the importance of longitudinal orthopedic surveillance, proactive bone health management beginning in childhood, and multidisciplinary care incorporating rehabilitation strategies to optimize long-term musculoskeletal outcomes.