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

Abstract

In the past couple of decades, literature in pediatric neurology and clinical genetics has identified hundreds of monogenic disorders that can masquerade as infantile cerebral palsy (CP). Accurate and prompt diagnosis in such cases may be challenging due to several reasons. There are commercial multigene CP panels, but their diagnostic yield is often limited compared with exome sequencing because of diverse etiologies that may mimic CP. We report one such case where a patient with spastic hemiplegia underwent a long diagnostic journey before genetic diagnosis was established with exome sequencing and appropriate management was started. TTC19-related mitochondrial complex III deficiency is an ultrarare disorder of energy metabolism that presents with bilateral lesions in the basal ganglia and a degenerative neuropsychiatric phenotype.