Researchers have identified a new autosomal recessive neurodevelopmental syndrome, which is characterised by global developmental delay, seizures, and intellectual disability.
In the journal Elife, the international team of scientists reports on two children in Jordan who presented with global neuro-developmental delay with frequent seizures and convulsions. The two affected siblings had no dysmorphic features but failed to develop the ability to walk or speak. They displayed progressive psychomotor retardation with hypotonic muscles. Electroencephalogram (EEG) analysis revealed abnormal epileptiform transients, consistent with frequent myoclonic seizures. Serum metabolite levels were normal, ruling out potential lysosomal storage disorders.
After performing identity-by-descent (IBD) homozygosity mapping using genomic DNA from both parents, two affected probands and three healthy siblings, the team determined that the disease is caused by a biallelic germline mutation in CAMK2A, which plays critical roles in synaptic plasticity and has been shown to be essential for learning and memory.
Several studies have previously shown that somatic mutations in human CAMK2 isoforms may contribute to neurological disorders. The authors of this new research say their “discovery of a novel neuro-developmental syndrome caused by biallelic CAMK2A mutations further broadens the spectrum of human neurological disorders caused by the CAMK2 family of kinases”.