HACE1, RAC1, and what else in the pathogenesis of SPPRS?

Spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) is a complex neurodevelopmental disorder with an autosomal recessive inheritance. SPPRS typically shows an infantile onset, starting with hypotonia either at birth or by age 3–4 months, followed by severely impaired global development and delayed early motor milestones.1 All patients with SPPRS develop slowly progressive bilateral lower limb spasticity, leaving them wheelchair bound and bed bound by their 20s. In some cases, patients may never walk. Most patients develop seizures in childhood and have a speech delay. Other variable features include ocular abnormalities, sensorineural hearing loss, skeletal abnormalities, obesity, and double incontinence. Some male patients have hypoplastic genitalia. Brain imaging may show generalized cerebral atrophy, ventricular dilatation, hypoplasia of the corpus callosum, and decreased white matter.1