MEDNIK syndrome

MEDNIK syndrome (OMIM#609313),^[1] also known as "syndrome de Kamouraska" (syndrome from Kamouraska), is a genetic disorder that is caused by mutations to the AP1S1 gene. Transmission of the disease is believed to be autosomal recessive. Symptoms of the syndrome are intellectual disability, enteropathy, deafness, neuropathy, ichthyosis, and keratoderma (MEDNIK).^[2][3] People with MEDNIK syndrome often have a high forehead, upslanting palpebral fissures, a depressed nasal bridge, low-set ears, growth retardation, and brain atrophy apparent upon imaging.^[4] The disorder was discovered by Patrick Cossette and his research team from the Université de Montréal. MEDNIK syndrome was initially reported in a few French-Canadian families near Quebec who all shared common ancestors.^[2]

MEDNIK syndrome has been shown to create a defect in copper metabolism. Before MEDNIK, the only two inherited copper metabolism disorders known were Menkes disease and Wilson's disease.^[2] Menkes and Wilson's disease are both caused by mutations in copper ATPases that are distinct for each disease. Both ATPases, ATP7A (Menkes) and ATP7B (Wilson's) are located in the trans-Golgi network and are responsible for transporting copper to cuproenzymes synthesized within the secretory compartments.^[2] Patients with MEDNIK syndrome have been shown to display combined clinical and biochemical signs of both Menkes and Wilson's diseases.^[2]

The transport of copper, recycling of copper ATPases, and copper detoxification are reliant on proper intracellular copper trafficking. The defect in the AP1S1 gene causes improper function and trafficking of copper ATPases resulting in less retention in the trans-Golgi and excess copper in the plasma membrane.