The first symptoms of PME with ataxia syndrome (or EPM-1B) usually involve problems with balance and coordination around 3-4 years of age. Therefore children may have trouble walking and they may fall frequently; moreover they might show hand tremor while performing actions.
Usually between 5 and 10 years of age, children begin having recurrent seizures (epilepsy). The seizures can be extremely variable, for example involving abnormal movements of a single arm or instead of the entire body, with or without loss of consciousness. They often occur at night while the child is asleep. Sometimes children may also suddenly fall to the ground, because of a seizure. In some cases epileptic seizures are triggered by flashing lights or contrasting light and dark patterns.
People with PME with ataxia syndrome may also show involuntary muscle jerks or twitches (myoclonus), sometimes triggered by specific movements, difficulties talking (dysarthria) and/or eating and drinking (dysphagia), problems with vibration and position sense, difficulties in eye movements.
In contrast with other types of PME, PRICKLE1-related PME with ataxia usually there is no severe impairment of intellectual abilities. A few affected individuals died during childhood, but many have lived into adulthood. However, the movement problems are often worsening, so that in some cases patients become wheelchair-bound.
In patients with this syndrome brain scans (e.g. CT, MRI) are usually normal, while other investigations (e.g. EEG) may show findings not specific for this condition.
Notably, mutation of PRICKLE1 can lead to many different conditions, beside the just described PME-ataxia syndrome, however there are very few patients with these characteristics, therefore it is difficult to generalize these findings. In scientific literature the following rare conditions related to PRICKLE1 mutations have been described: patients with brain and other nervous system malformations; individuals with seizures but without ataxia; a very early-onset (10 months) and severe drug-resistant epilepsy, associated with ataxia and intellectual disability; a case of sudden unexpected death due to epilepsy in a previously healthy adult individual; a case characterized by seizures and autism. Sometimes, these atypical conditions result from new, not inherited mutations in the PRICKLE1 gene.
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