Introduction:
Early-onset epileptic encephalopathies are among the most severe early-onset epilepsies, leading to progressive neurodegeneration. An increasing number of novel genetic causes continue to be uncovered as the primary etiology.
Results:
We report a girl infant of Semitic (Saudi Arabian) descent who presented with multifocal seizures and later developed intractable infantile spasms and myoclonic seizures. Her clinical features and electroencephalography were consistent with early-onset epileptic encephalopathy. Whole exome sequence analysis showed homozygous novel pathogenic variant (variant p.Q287PfsX27; coding DNA c.858_862delACAAA) in the SYNJ1 gene.
Conclusion:
This is a newly described early-onset epileptic encephalopathy secondary to a critical reduction of the dual phosphatase activity of SYNJ. Clinical features include early-onset intractable focal, myoclonic seizures, infantile spasms, and hypotonia progressing to spastic quadriparesis, opisthotonus, dystonia, profound developmental delay, and a progressive neurodegenerative course. Brain magnetic resonance imaging is usually normal. Electroencephalography shows diffuse slowing with multifocal epileptiform discharges or modified hypsarrhythmia. These findings further expand the clinical spectrum of synaptic dysregulation in patients with severe epilepsy and emphasize the importance of this biological pathway in seizure pathophysiology.