MEDNIK syndrome

MEDNIK is the acronym for Mental Retardation, Enteropathy, Deafness, Peripheral Neuropathy, Ichthyosis, and Keratoderma. MEDNIK syndrome is a rare autosomal recessive disorder characterized by mental retardation, ichthyosis, hearing loss, peripheral neuropathy, enteropathy, and keratoderma.

Prevalence: <1 / 1 000 000

The disease is caused by mutations in the AP1S1 gene , which is located on chromosome 7 at gene locus q22.1. AP1S1 encodes the subunit Sigma1a of the AP-1 complex, which plays a role in the assembly of the clathrin envelope and in transport between the trans-Golgi network, endosomes and the plasma membrane.

Apparently, different mutations in AP1S1 lead to different phenotypes. At one time, loss of AP1S1 function can lead to a defect in the intestinal epithelial barrier and a nonsyndromic form of congenital diarrhea, whereas other truncating AP1S1 mutations cause MEDNIK syndrome, which is characterized by mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratoderma.

In the case of the patient of Incecik F et al (2018) with MEDNIK syndrome, sequencing of the AP1S1 gene revealed a homozygous insertion c.364dupG (NM_001283.4) resulting in a frameshift of the reading frame (p.D122Gfs*18).

1. Incecik F et al. (2018) MEDNIK syndrome with a frame shift causing mutation in AP1S1 gene and literature review of the clinical features. Metab Brain Dis 33:2065-2068.
2. Klee KMC et al (2020) AP1S1 missense mutations cause a congenital enteropathy via an epithelial barrier defect. Hum Genet 139:1247-1259.
3. Martinelli D et al. (2014) AP1S1 defect causing MEDNIK syndrome: a new adaptinopathy associated with defective copper metabolism. Annals of the New York Academy of Sciences 1314: 55-63.
4. Martinelli D et al. (2013) MEDNIK syndrome: a novel defect of copper metabolism treatable by zinc acetate therapy. Brain 136: 872-881
5. Saba TG et al (2005) An atypical form of erythrokeratoderma variabilis maps to chromosome 7q22. Human genetics 116: 167-171.