The three patients with the de novo mutations, whose ages ranged from 4 to 11 years, had similar clinical profiles (Table 2, and the Supplementary Appendix). They were all born to nonconsanguineous parents after uneventful pregnancies and deliveries. Their early development was characterized by global delay and hypotonia, with the onset of walking at the age of 2 years. Scores on the Mullen Scales of Early Learning and the Vineland Adaptive Behavior Scales showed profiles that were consistent with moderate-to-severe mental retardation in all patients. Nonverbal social interactions were within the normal range. In particular, evaluation of Patient 3 with the Autism Diagnostic Observation Schedule was negative. Ophthalmologic assessment revealed a strabismus in Patient 1. Two of the patients were mildly epileptic. Patient 1 had brief, generalized tonic–clonic seizures and was seizure-free while taking topiramate, whereas Patient 2 had some myoclonic and absence seizures, which were well controlled with valproate. In both patients, electroencephalography revealed bioccipital spikes during intermittent light stimulation.
