Characteristic clinical findings:
• Early-onset motor delay with delayed motor milestones, often with failure to achieve independent ambulation
• Impaired or absent speech development
• Neonatal/infantile hypotonia (usually mild)
• Progressive spasticity and pyramidal signs
• Postnatal microcephaly (usually in -2SD to -3SD range)
• Early-onset seizures including frequent febrile seizures
• Episodes of stereotypic laughter
• Short statue
• Foot deformities
• Brain imaging findings: Thinning of the corpus callosum (with prominent thinning of the posterior parts), abnormal myelination and nonspecific loss of the periventricular white matter, ex-vacuo ventriculomegaly, often with prominent enlargement of the posterior horns of the lateral ventricles
AP4E1