Yunis–Varon syndrome

Yunis–Varon syndrome (YVS), also called cleidocranial dysplasia with micrognathia or absent thumbs and distal aphalangia, is an extremely rare autosomal recessive multisystem congenital disorder which affects the skeletal system, ectodermal tissue, heart and respiratory system. It was first described by Emilio Yunis and Humberto Váron from the National University of Colombia.

Signs and symptoms

Genetics

This syndrome is inherited in an autosomal recessive manner. Several mutations in the FIG4-encoding gene were found to cause Yunis–Varon syndrome. Some of these mutations result in complete loss of protein function; others involve amino-acid replacements at highly conserved residues. Not all mutations in the FIG4 gene result Yunis–Varon syndrome. Some mutations lead to various forms of Charcot–Marie–Tooth disease, Amyotrophic lateral sclerosis 11, and bilateral temporooccipital polymicrogyria.

Patients affected with Yunis–Varon syndrome are homozygous, compound homozygous, or compound heterozygous for deleterious mutations in FIG4.

Animal model

Spongiform degeneration of mouse brains caused by altering PI3P to PI(3,5)P2 conversion is associated with human Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis (ALS) by accumulation of Lc3II, p62, and LAMP2 proteins, which also contributes to inclusion body disease. Manipulation of this signaling lipid involves culturing fibroblasts obtained by insertion of ETn2-beta(early transposon 2-beta) into intron 18 of FIG4 gene in vacuolar membrane of mice labeled pale tremor (plt).