Neurodevelopmental disorder with dystonia due to SOX6 mutations

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• SOX6 gene mutations are a newly identified cause of neurodevelopmental disorders.
• These disorders present with intellectual disability, behavioral changes, and skeletal abnormalities.
• Fewer than 25 cases of SOX6-associated disorders have been documented.

Observation:

• A novel case of SOX6-associated neurodegeneration is presented.
• The patient exhibited early-onset intellectual decline, facial asymmetry, and dystonic tremor.
• Skeletal findings included scoliosis and mandibular coronoid process hypertrophy.

Findings:

• A de novo loss-of-function variant (c.277 C>T, p.Arg93*) in SOX6 was identified.
• This variant causes N-terminal protein truncation, affecting SOX6 function.
• The patient's symptoms, including tremor, showed significant improvement with levodopa treatment.

Implications:

• SOX6-associated neurodevelopmental delay is extremely rare.
• The phenotype is expanded to include ceratoconus and dystonic tremor responsive to levodopa.
• Consider SOX6 mutations in patients with complex dystonia parkinsonism due to therapeutic potential.