Abstract
BACKGROUND: Synaptojanin 1 is encoded by the SYNJ1(MIM 604297) and plays a major role in phosphorylation and recycling of synaptic vesicles. Mutation of SYNJ1 is associated with two distinct phenotypes; a known homozygous missense mutation (p.Arg258Gln) associated with early-onset Parkinson disease (MIM 615530), whereas mutation with complete loss of SYNJ1 function result in a lethal neurodegenerative disease with intractable seizure and tauopathies (MIM 617389). METHODS: We report two related children from consanguineous family presented with intractable seizure, profound developmental delay, failure to thrive, acquired microcephaly, and hypotonia. The brain MRI is normal and EEG showed hypsarrhythmia. RESULT: The diagnosis was achieved via whole-genome sequencing which showed homozygous mutation in SYNJ1 (c.709C>T, p.Gln237*). CONCLUSION: A clinical pattern of neonatal-onset intractable seizure, profound developmental delay, muscular hypotonia, hypsarrhythmia, and no focal abnormality of brain MRI should prompt initiation of molecular genetic analysis of SYNJ1. Establishment of the diagnosis permits genetic counseling, prevents patients undergoing unhelpful diagnostic procedures and allows for accurate prognosis.