Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy, commonly known as PLOSL, is a progressive disorder that affects the bones and brain.  "Polycystic lipomembranous osteodysplasia" refers to cyst-like bone changes that can be seen on x-rays.  "Sclerosing leukoencephalopathy" describes specific changes in the brain that are found in people with this disorder.

Variants (also called mutations) in the TREM2 gene or the TYROBP gene can cause PLOSL. The proteins produced from these two genes work together to activate certain kinds of cells. These proteins appear to be particularly important in osteoclasts, which are specialized cells that break down and remove (resorb) bone tissue that is no longer needed. Osteoclasts are involved in bone remodeling, which is a normal process that replaces old bone tissue with new bone. The TREM2 and TYROBP proteins are also critical for the normal function of microglia, which are a type of immune cell in the brain and spinal cord (central nervous system). Although these proteins play essential roles in osteoclasts and microglia, their exact function in these cells is unclear.

PLOSL is a very rare condition. It was first reported in the Finnish population, where it has an estimated prevalence of 1 to 2 per million people. This condition has also been diagnosed in more than 100 people in the Japanese population. Although affected individuals have been reported worldwide, PLOSL appears to be less common in other countries.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Published Date: October 17, 2023
Published By: National Institutes of Health