Clinical Characteristics

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