Limitations of Multigene Next-Generation Sequencing Panel for "Cerebral Palsy" Phenotype and Other Complex Movement...

Area of Science:

• Genetics
• Neurology
• Metabolic Disorders

Background:

• Hundreds of monogenic disorders mimic infantile cerebral palsy (CP), complicating diagnosis.
• Commercial gene panels have limited diagnostic yield for CP mimics due to diverse causes.
• Accurate diagnosis is crucial for appropriate management and treatment.

Purpose of the Study:

• To highlight the diagnostic challenges in identifying genetic disorders presenting as CP.
• To report a case of TTC19-related mitochondrial complex III deficiency mimicking CP.
• To emphasize the utility of exome sequencing in diagnosing rare genetic conditions.

Main Methods:

• Case report of a patient with spastic hemiplegia.
• Diagnostic journey including clinical evaluation and genetic testing.
• Exome sequencing to identify the underlying genetic cause.

Main Results:

• A patient with spastic hemiplegia was diagnosed with TTC19-related mitochondrial complex III deficiency.
• This ultrarare disorder of energy metabolism presented with basal ganglia lesions and a degenerative neuropsychiatric phenotype.
• Exome sequencing was key to establishing the genetic diagnosis after a prolonged diagnostic process.

Conclusions:

• TTC19-related mitochondrial complex III deficiency is a rare genetic disorder that can present as infantile cerebral palsy.
• Exome sequencing is a powerful tool for diagnosing complex neurological conditions with diverse etiologies.
• Early and accurate genetic diagnosis is essential for initiating appropriate management in pediatric neurological disorders.