Sensory ataxia, wide-based gait, and Rombergism emerge by age 4. Signs of sensory neuropathy include pan-areflexia, stockingglove loss of vibration and position sense, astereognosia, agraphesthesia, and blunted sensation of applied force. Muscle tone, power, and electromyography are normal. MRI reveals T2 signal hyperintensity running the length of the dorsal spinal cord. Sensory sural nerve action potentials and H waves are absent. Some patients develop focal epilepsy marked by interictal focal spike-wave discharges. Cognitive function is normal. Affected neonates are hypotonic and feed poorly. Dysmorphic features that evolve over time include a bulbous nose, wide mouth and tongue, broad jaw with protuberant angles, short hands, short tapered fingers, and broad CHIR-99021 cost thumbs. Affected children have severe psychomotor delay and do not learn to walk or speak. Many retain use of their hands to scoot, maneuver a wheelchair, or gesture. Some children show behavioral responses to language, but they do not socially engage or follow verbal commands. Examination typically reveals a subdued child with strabismus, slow horizontal nystagmus, hypotonia, and weak or absent tendon reflexes. Magnetic resonance imaging reveals ventriculomegaly, thin corpus callosum, white matter abnormalities, and an undulating or ����lumpy���� skull surface. The cortical ribbon follows the irregular skull contour. Multifocal spike-wave discharges from central, occipital, and temporal regions typically begin by 6 months of age and are accompanied by focal or generalized seizures that can manifest as dystonic posturing, drop attacks, myoclonic jerks, or generalized tonic-clonic events. Multiple intractable seizure types can afflict an individual patient. Physical anomalies found in some patients include subglottic stenosis, aortic stenosis, bicuspid aortic valve, umbilical hernia, and hydrocele. Growth and development are normal during infancy. Visual impairment becomes evident during early childhood with the emergence of fine horizontal nystagmus, light aversion, and optic pallor. As vision deteriorates, fundoscopic exam reveals marked attenuation of retinal arteries and veins, pigmentary changes and a cellophane-like reflex that produce ����bull��s eye���� maculae and diffuse pigmentary stippling of the R428 peripheral retinae, consistent with retinitis pigmentosa. This constellation suggests a combination of optic nerve disease, retinal dystrophy, and cone dysfunction. Patients are typically blind by the second or third decade of life but the pace of visual deterioration is highly variable. We do not have auditory data from affected newborns, but some auditory function is present during infancy and deteriorates during early childhood; all five evoked auditory waveforms are absent by age 5. Amplifiers or cochlear implants can partially restore hearing.