NeurometPlus

Incidence

PLOSL is inherited in an autosomal recessive manner. The prevalence of PLOSL is highest in Finland with an estimated prevalence of 1-2 x 10-6. Incidence is lower in other countries, most patients have been diagnosed in Japan (over 100 cases).

Clinical Characteristics

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures due to radiologically demonstrable bone cysts, frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages: 1) Latent stage with normal early development; 2) Osseous stage (third decade of life), characterized by pain and tenderness, mostly in ankles and feet, usually following strain or injury. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities; 3) Early neuropsychiatric stage (fourth decade of life). A change of personality begins to develop insidiously in the fourth decade. Patients show progressive loss of judgement, leading to serious social problems; 4) Late neuropsychiatric stage, characterized by loss of mobility, apathy, and death in the early 40s. The clinical course of PLOSL can be divided into four stages: 1) latent, 2) osseous, 3) early neuropsychiatric, and 4) late neuropsychiatric. 1) Latent stage. The early development of the individuals is normal. 2) Osseous stage (third decade of life). The first symptoms of PLOSL appear in early adulthood as pain and tenderness, mostly in ankles and feet, usually following strain or a minor accident. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities. The first fractures usually occur shortly before age 30 years; however, patients may have been experiencing pain and swelling of the ankles and wrists after strain for years. The fractures heal well. It is important to note that some patients may present with neuropsychiatric symptoms without any preceding osseous problems. 3) Early neuropsychiatric stage (fourth decade of life). A change of personality begins to develop insidiously in the fourth decade. Patients show progressive loss of judgment, leading to serious social problems such as divorce, unemployment, and financial trouble. Some patients may attempt suicide. Subsequently the full-blown picture of the frontal lobe syndrome appears: loss of judgment, euphoria, lack of social inhibitions (including Witzelsucht), disturbance of concentration, and lack of insight, libido, and motor persistence. Progressive signs of upper motor neuron involvement (spasticity, extensor plantar reflexes) are noticed. With advancing disease, lack of initiative and activity conceal the aforementioned symptoms. Memory disturbances begin at approximately the same age as the personality changes, and are best detectable by psychometric tests (Benton's Visual Retention Test, Ten-word test, and WMSc). The memory disturbance is less severe than the personality change, and patients are able to maintain the most important personal data until the last stage of the disease. Other disturbances of higher cortical function, such as motor aphasia, agraphia, acalculia, and apraxia, appear only at the last stage of the disease. Patients may develop postural dyspraxia: they walk or sit in peculiar skewed postures. Involuntary athetotic or choreatic movements or myoclonic twitches are common. Patients who reach their mid-thirties frequently experience epileptic seizures. In some patients, impotence or lack of libido and urinary incontinence are among the first symptoms. 4) Late neuropsychiatric stage. In the last stage of the disease, the individuals lose their ability to walk, usually by age 40 years. Finally, patients lie without any active movements in a decerebrate state. Primitive reflexes, such as visual and tactile grasp and mouth opening reflexes, as well as the sucking reflex, may become noticeable. Patients typically die in their early 40s.

Precipitants

none

Provocation Tests

none

Diagnostic Procedures

The combination of radiologically demonstrable polycystic osseous lesions, frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade, is diagnostic. Fractures of the wrists or ankles after minor trauma with typical polycystic osseous lesions identified on x-ray examination suggest the possibility of PLOSL. In the fourth decade of life, patients develop a frontal lobe syndrome, manifested by euphoria and loss of social inhibitions. Progressive dementia sets in at the same time. Dementia is mild at the onset of the neuropsychiatric symptoms. The disease culminates in severe dementia; patients typically die in their early 40s. Diagnosis/testing: The combination of radiologically demonstrable polycystic osseous lesions, frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade is diagnostic. Fractures of the wrists or ankles after minor trauma with typical polycystic osseous lesions identified on x-ray examination suggest the possibility of PLOSL. In uncertain cases, bone biopsy helps to establish the diagnosis. Molecular genetic testing of the DAP12 gene (chromosomal locus 19q13.1) detects mutations in 100% of affected Finnish individuals and a lower proportion of non-Finnish individuals. All Finnish patients with PLOSL are homozygous for a 5.3 kb deletion including exons 1-4 of DAP12. Such testing is available on a research basis only.