Work

Feeding-Triggered Seizures in a Newborn with AP1S1-Related MEDNIK Syndrome: Expanding the Phenotype of a Hyper-Rare Disease

Year: 2025

Type: article

Abstract: MEDNIK syndrome (Mental Retardation, Enteropathy, Deafness, Neuropathy, Ichthyosis and Keratodermia) is a severe hyper-rare condition resulting from the biallelic variants in the AP1S1 gene, implicated in intracellular trafficking and copper homeostasis. Only 18 affected individuals (seven AP1S1 pathogenic variants overall) have been reported to date, with a high early lethality due to life-threatening congenital enteropathy. Seven patients have been empirically treated with zinc. Due to the paucity of literature data, little is known about the clinical course of individuals affected by MEDNIK syndrome, and the possible early association with epilepsy needs to be investigated. We present the first case of Italian origin affected by MEDNIK syndrome carrying a new homozygous AP1S1 stop variant, presenting with congenital severe enteropathy and feeding-related seizures, thus representing an early, singular manifestation of the disease. We describe her clinical course and the zinc acetate therapeutic experience. We also reviewed the literature focusing on clinical manifestations (especially neurological), brain neuroimaging and the symptom evolution of patients with AP1S1-related MEDNIK syndrome and discuss possible future therapeutic attempts.

Source: Journal of Clinical Medicine

DOI: 10.3390/jcm15010106