Unveiled SOX2 disorder in a child initially diagnosed as cerebral palsy

Abstract Background SOX2 disorder is a genetic disorder caused by disease-causing variants of the SOX2 located on chromosome 3q26.3-q27.1. SOX2 disorder is clinically characterized by severe eye malformations but is also associated with developmental delay, intellectual disability, and spastic or dystonic movements, which can mimic cerebral palsy (CP). We present the case of a child with a de novo SOX2 pathogenic variant showing spasticity and dystonic movement but no major ocular phenotype, initially diagnosed as CP. Case presentation An 8-year-old Korean girl was referred to the Medical Genetics and Rare Disease Center due to developmental delays, spasticity, dystonia, and an unsteady gait. Born at 35 weeks of gestation with a birth weight of 2.17 kg, she had non-consanguineous parents and no family history of hereditary disorders. Diagnosed with bilateral mixed-type CP (spastic and dyskinetic) at age 3, she received physical and occupational therapies and botulinum toxin injections. At referral, she walked independently with ankle–foot orthoses. Neurological examination revealed exaggerated deep tendon reflexes, spasticity in the lower limbs and dyskinetic movements in all extremities. Laboratory tests were normal, and brain and cervical spine MRI showed no abnormalities. Due to the discrepancy between clinical and radiological findings, genetic tests were performed. Chromosome analysis, microarray, and targeted gene sequencing did not reveal any abnormal findings. Whole-genome sequencing identified a de novo heterozygous variant in SOX2 (NM_003106.4.310G > T), resulting in a nonsense variant (p.Glu104Ter) classified as pathogenic variant. Sanger sequencing confirmed the variant. Conclusion We report the first case of an atypical SOX2 disorder with the pathogenic variant presenting primarily as spasticity and dystonic movements without ocular symptoms. This case highlights the importance of considering a genotype-based approach in suspected CP mimics. The identification of a SOX2 disease-causing variant expands the understanding of SOX2 disorders and suggests that SOX2 may be a potential candidate gene for CP.