Universal features are infant hypotonia, motor and communication delay preceding intellectual disability, and abnormal EEG (low frequency, high amplitude oscillations with or without epileptiform features). Ophthalmic problems such as squint and nystagmus are also very common, and cerebral visual impairment is likely to remain functionally important. Epileptic seizures appear to be an uncommon feature, and structural MRI is usually normal. Developmental progress is very variable, with prolonged communication and educational difficulties.
Around half of patients develop a hyperkinetic involuntary movement disorder, which worsens during later childhood. Other patients develop ataxia. Motor stereotypies are very common, and patients seem to have a particular tendency to bite or chew on their hands and fingers. Some patients develop a very disrupted sleep pattern, with frequent waking and long periods of wakefulness. A range of emotional and behavioral difficulties have been reported, including unprovoked episodes of distress / agitation / screaming. Older patients can experience anxiety, obsessions and prolonged low mood.
Medical problems that affect some patients include gastro-esophageal reflux, progressive scoliosis and contractures. A smaller number of patients have experienced abnormal respiratory patterns, such as apneic episodes or hyperventilation.