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Genetics Home Reference: your guide to understanding genetic conditions     A service of the U.S. National Library of Medicine®

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

(often shortened to PLOSL)
Reviewed November 2008

What is PLOSL?

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.

The bone abnormalities associated with PLOSL usually become apparent in a person's twenties. In most affected individuals, pain and tenderness in the ankles and feet are the first symptoms of the disease. Several years later, broken bones (fractures) begin to occur frequently, particularly in bones of the ankles, feet, wrists, and hands. Bone pain and fractures are caused by thinning of the bones (osteoporosis) and cyst-like changes. These abnormalities weaken bones and make them more likely to break.

The brain abnormalities characteristic of PLOSL typically appear in a person's thirties. Personality changes are among the first noticeable problems, followed by a loss of judgment, feelings of intense happiness (euphoria), a loss of inhibition, and poor concentration. These neurologic changes cause significant problems in an affected person's social and family life. As the disease progresses, it causes a severe decline in thinking and reasoning abilities (dementia). Affected people ultimately become unable to walk, speak, or care for themselves. People with this disease usually live only into their thirties or forties.

How common is PLOSL?

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.

What genes are related to PLOSL?

Mutations in the TREM2 gene or the TYROBP gene (also called DAP12) 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. These cells 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.

Mutations in the TREM2 or TYROBP gene disrupt normal bone growth and lead to progressive brain abnormalities in people with PLOSL. Researchers believe that the bone changes seen with this disorder are related to malfunctioning osteoclasts, which are less able to resorb bone tissue during bone remodeling. In the central nervous system, TREM2 or TYROBP mutations cause widespread abnormalities of microglia. Researchers are working to determine how these abnormalities lead to the progressive neurological problems associated with PLOSL.

Related Gene(s)

Changes in these genes are associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy.

  • TREM2

How do people inherit PLOSL?

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

Where can I find information about diagnosis or management of PLOSL?

These resources address the diagnosis or management of PLOSL and may include treatment providers.

  • Gene Review: Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL) (
  • Genetic Testing Registry: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (
  • MedlinePlus Encyclopedia: Dementia (

You might also find information on the diagnosis or management of PLOSL in Educational resources and Patient support.

General information about the diagnosis ( and management ( of genetic conditions is available in the Handbook. Read more about genetic testing (, particularly the difference between clinical tests and research tests (

To locate a healthcare provider, see How can I find a genetics professional in my area? ( in the Handbook.

Where can I find additional information about PLOSL?

You may find the following resources about PLOSL helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for PLOSL?

  • Nasu-Hakola disease
  • NHD
  • PLO-SL
  • Presenile dementia with bone cysts

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines ( and How are genetic conditions and genes named? ( in the Handbook.

What if I still have specific questions about PLOSL?

Ask the Genetic and Rare Diseases Information Center (

What glossary definitions help with understanding PLOSL?

autosomal ; autosomal recessive ; bone remodeling ; cell ; central nervous system ; cysts ; dementia ; gene ; inherited ; leukoencephalopathy ; microglia ; nervous system ; neurologic ; neurological ; osteoporosis ; population ; prevalence ; recessive ; tissue ; white matter ; x-rays

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.


  • Gene Review: Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL) (
  • Klünemann HH, Ridha BH, Magy L, Wherrett JR, Hemelsoet DM, Keen RW, De Bleecker JL, Rossor MN, Marienhagen J, Klein HE, Peltonen L, Paloneva J. The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2. Neurology. 2005 May 10;64(9):1502-7. (
  • Kondo T, Takahashi K, Kohara N, Takahashi Y, Hayashi S, Takahashi H, Matsuo H, Yamazaki M, Inoue K, Miyamoto K, Yamamura T. Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms. Neurology. 2002 Oct 8;59(7):1105-7. (
  • Madry H, Prudlo J, Grgic A, Freyschmidt J. Nasu-Hakola disease (PLOSL): report of five cases and review of the literature. Clin Orthop Relat Res. 2007 Jan;454:262-9. Review. (
  • Paloneva J, Autti T, Raininko R, Partanen J, Salonen O, Puranen M, Hakola P, Haltia M. CNS manifestations of Nasu-Hakola disease: a frontal dementia with bone cysts. Neurology. 2001 Jun 12;56(11):1552-8. (
  • Verloes A, Maquet P, Sadzot B, Vivario M, Thiry A, Franck G. Nasu-Hakola syndrome: polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy and presenile dementia. J Med Genet. 1997 Sep;34(9):753-7. Review. (


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? ( in the Handbook.

Reviewed: November 2008
Published: February 8, 2016