Case report: Early-onset parkinsonism among the neurological features in children with PHACTR1 variants

Area of Science:

• Genetics and Neurology
• Molecular Biology

Background:

• The PHACTR1 gene is expressed in cardiovascular and neurological tissues, playing a role in brain maturation.
• Previously identified PHACTR1 mutations in patients were associated with early-onset epilepsy and intellectual disability.

Observation:

• Two new cases of de novo pathogenic variants in PHACTR1 were identified, presenting with early-onset developmental and epileptic encephalopathy.
• One patient exhibited a progressive movement disorder (hypertonus, hypo-bradykinesia, hypomimia, ataxic gait, retropulsion) and a speech disorder, unresponsive to levodopa treatment.

Findings:

• PHACTR1 variants can manifest with either cardiological or neurological phenotypes.
• Severe developmental delay, intellectual disability, and early-onset epileptic encephalopathy are characteristic neurological features.
• The newly observed movement and speech disorders may represent novel aspects of the PHACTR1-related neurological phenotype.

Implications:

• Expanding the understanding of the PHACTR1 gene's role in neurological development and disease.
• Highlighting the potential for PHACTR1 mutations to cause a broader spectrum of neurological symptoms than previously recognized.
• Informing future diagnostic and therapeutic strategies for patients with PHACTR1-associated disorders.