The proband cannot speak or use her hands to communicate, and it has thus been difficult to assess cognitive function or thought content. Seizures are only partially responsive to anticonvulsants and not affected by high-dose pyridoxine. Affected children have stagnant head growth, remain visually inattentive, do not feed independently, and make no developmental progress. They have frequent spontaneous apnea and bradycardia that uniformly culminates in cardiopulmonary arrest before age 4 months. The brain of a child who died at 4 weeks of age weighed 382 grams but was otherwise normally developed. Primary lesions were localized to most regions of the corpus striatum and cerebral cortex with relative sparing of the anterior caudates and parietal lobes. Lesions consisted of neuronal loss associated with a striking microglial reaction and proliferation of Alzheimer type 2 astrocytes. The phenotype was originally described by Victor McKusick. All patients are born with microcephaly, a sloping forehead, diminutive anterior fontanelle, and sutural ridging. Head circumference is more than 4 standard deviations below normal at birth and remains so into adulthood. Affected neonates transition well and feed normally. Children walk independently between 14 and 36 months of age and language emerges at an appropriate age but remains rudimentary. Cognitive impairment ranges from moderate to severe ; intelligence Temozolomide 85622-93-1 quotients of two young patients were 60 and 62. Two of nine patients have epilepsy: one started having drop attacks in late childhood and another Talazoparib PARP inhibitor developed nocturnal epilepsy as an adult. Magnetic resonance imaging shows diffuse pachygyria. The cerebral hemispheres are small relative to the cerebellum, which has a hypoplastic vermis. Although myelin volume appears reduced, it has normal signal quality. The surface area of the corpus callosum is approximately half that of an agematched control child. Visual impairment becomes evident during the first year of life. The retina and choroid are underdeveloped and have focal defects that reveal bare sclera. Just posterior to the equator of the eye, much of the retina has a scalloped appearance that suggests focal areas of arrested development. The more anterior parts of the retina, near the periphery and pars plana, have a grayish hue and diminutive vasculature similar to retinopathy of prematurity. Condensations of vitreous may attach to the retina in transition regions between scalloped and gray tissue, marking points of traction for retinal detachment. The AXPC1 phenotype has been described elsewhere. Tunnel-like visual loss and photophobia begin early in childhood when fundoscopy reveals signs of non-spiculated retinitis pigmentosa and cellophane maculopathy. As vision deteriorates throughout adolescence, patients might develop posterior subcapsular cataracts. Motor milestones are slightly delayed.