This website provides information on patients with mutations in the PLAAgene, including clinical data, molecular data, management and research options.
The syndrome caused by mutations in the PLAAgene is a multisystem disorder characterized by
a severe infantile-onset syndrome characterized by:
• Progressive microcephaly
• Spastic quadriparesis (central hypotonia with peripheral hypertonia)
• Seizures/epileptic encephalopathy (reported in ~73% of cases)
• Global developmental delay and cognitive impairment
• Failure to thrive, feeding difficulties, and dysphagia
• Brain MRI abnormalities including leukoencephalopathy and widened subarachnoid spaces
Onset typically occurs between birth and 4 months of age. The most severe phenotypes, including early lethality, are associated with mutations in the WD40 domain, while PUL domain mutations (e.g., Leu752Phe) may allow survival into the teens or adulthood.
More recently, de novo monoallelic (heterozygous) missense variants in the PUL domain have been identified in children with milder neurodevelopmental disorders including psychomotor regression, intellectual disability, and autism spectrum disorders, expanding the phenotypic spectrum.
Plaa-null mice are perinatal lethal with reduced brain prostaglandin E levels, confirming the gene's essential role in CNS development.
Not all individuals with a mutation in the PLAAgene have these features.
This website was created to share and collect information about clinic, management and research projects to gather more knowledge and provide better treatment of patients with mutations in the PLAAgene.
Ali Reza Tavasoli, MD, Tehran University of Medical sciences, Tehran, Iran, alirezatavasoli236@gmail.com
Arastoo Kaki, PhD, Hamedan University of Medical sciences, Hamedan, Iran, kaki.arastoo@gmail.com
PLAA