CASE REPORT: PURA SYNDROME CAUSED BY A DE NOVO c.345_346del VARIANT IN A 6-YEAR-OLD BOY WITH REFRACTORY EPILEPSY AND DIAGNOSTIC DELAY

Abstract

Background: PURA syndrome is a rare neurodevelopmental disorder caused by heterozygous pathogenic variants in the PURA gene, characterized by neonatal hypotonia, epilepsy, and developmental delay. Diagnostic delay is common when acquired neonatal insults co-exist and mask the underlying genetic etiology. Methods: We describe a 6-year-old boy with a de novo PURA c.345_346del (p.Asp116LeufsTer84) variant identified by trio clinical exome sequencing after negative SCO2 sequencing and chromosomal microarray. Clinical course, EEFeG, neuroimaging, and 6-year follow-up were analyzed retrospectively. Results: The patient presented with hypotonia, feeding difficulties, and neonatal seizures complicated by bacterial meningitis, grade I intraventricular hemorrhage, and hyperbilirubinemia. Seizures evolved into refractory epilepsy with tonic, hypermotor, and focal impaired awareness seizures despite four antiseizure medications. Additional features included non-verbal status, GMFCS V, strabismus, cryptorchidism, and hypothyroidism requiring replacement therapy. Conclusion: Co-occurring acquired insults may mask monogenic etiology and prolong diagnostic odyssey. Early access to exome sequencing and multidisciplinary follow-up are critical for family counseling and care planning.