Endoscopic third ventriculostomy for diencephalosynapsis-related hydrocephalus in MPDZ gene syndrome: a case report and review of the literature

Abstract Purpose MPDZ syndrome is a rare autosomal recessive disorder caused by biallelic pathogenic variants in MPDZ (9p23) and typically managed with ventriculoperitoneal shunting (VPS). Recent characterization of MPDZ-related hydrocephalus as an obstructive process—driven by diencephalosynapsis and third ventricle atresia—provides theoretical grounds for endoscopic third ventriculostomy (ETV), yet no primary ETV treatment has previously been reported in a genetically confirmed, liveborn patient. Methods We report a female infant with prenatally diagnosed obstructive ventriculomegaly, subsequently confirmed as MPDZ syndrome by whole-exome sequencing, who was treated with ETV as the primary surgical intervention, and we review the literature on the neurosurgical management of MPDZ-related hydrocephalus. Results Fetal MRI demonstrated diencephalosynapsis and third ventricle atresia with secondary occlusion of the aqueduct of Sylvius. A ventriculo-amniotic shunt was placed at 29 weeks of gestation; the infant was born at 36 weeks and 1 day and underwent ETV on the fifth day of life without complications. At 2 years and 5 months of age, she developed intermittent symptoms of intracranial hypertension due to late stoma occlusion at the level of the Liliequist membrane, successfully managed with endoscopic stoma revision. At the most recent follow-up (4 years and 5 months), she remains free of ventriculoperitoneal shunting, with age-appropriate neurodevelopment. A systematic review of the literature identified no prior report of ETV used as primary treatment in a genetically confirmed, liveborn patient with MPDZ syndrome. Conclusions This case provides proof of concept that ETV is both mechanistically justified and clinically effective in selected patients with MPDZ-related obstructive hydrocephalus, potentially avoiding lifelong shunt dependency. Patient selection should nonetheless remain individualized, based on ventricular anatomy, third ventricular floor thickness, and associated structural anomalies.