Resources for Medical Professionals

PPP3CA Developmental Epileptic Encephalopathy (DEE91) is an ultra-rare genetic disorder caused by pathogenic variants in the PPP3CA gene (protein phosphatase 3 catalytic subunit alpha). The PPP3CA gene encodes a subunit for calcineurin, a calcium-dependent phosphatase abundant in the brain, which regulates synaptic vesicle recycling, synaptic plasticity, neuronal development, learning, and memory.

 

Variants in PPP3CA disrupt calcineurin's role in regulating neurotransmission and brain development, leading to impaired connectivity and abnormal electrical activity in the brain.

 

Three primary phenotypes have been identified based on the variant's location within the gene: catalytic, regulatory, or autoinhibitory domains. While symptoms often overlap across phenotypes, common clinical features include:

• Developmental delay and intellectual disability, often severe

• Refractory epilepsy

• Autism spectrum disorder

• Hypotonia

• Behavioral challenges

• Structural brain abnormalities

• Dysmorphic features and skeletal dysplasia

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PPP3CA mutations result in either Loss of Function (LoF) or a Gain of Function (GoF) depending on the variant's position and impact on protein function. LoF variants typically reduce or eliminate protein activity, while GoF variants enhance or dysregulate protein function, often by removing inhibitory control. Ongoing research is further defining these mechanisms and their clinical consequences. .

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For the most current medical literature and clinical resources, see the links below:

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Medical Professionals Kit​

Clinical Fact Sheet​

Research Papers