MEDNIK Syndrome (AP1S1)

MEDNIK Syndrome is an autosomal recessive disorder caused by pathogenic variants in AP1S1. As the protein encoded by AP1S1 is involved in regulating the transport of an ATP7A copper pump, pathogenic variants in the gene can lead to impaired copper metabolism and copper accumulation in the body’s organs, similar to Wilson disease and Menkes disease. The onset of symptoms of this condition occurs in infancy. MEDNIK is an acronym for the multiple systems impacted by the disorder: mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratoderma syndrome. Affected individuals have dysmorphic facial features, moderate to severe intellectual disability, enteropathy (disease of the intestine) with congenital diarrhea, sensorineural deafness, ichthyosis, hyperkeratosis, and erythroderma (widespread reddening of the skin). Liver disease can be caused by serum copper accumulation and result in hepatomegaly, liver fibrosis, and/or cirrhosis. Life expectancy may be reduced depending on the severity of the condition. Death in infancy has been reported due to severe diarrhea. No clear genotype-phenotype correlation has been established.

For information about carrier frequency and residual risk, please see the residual risk table.

This gene is included on the following panel(s):