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Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1(PLOSL1)

MedGen UID:
1648386
Concept ID:
C4721893
Disease or Syndrome
Synonyms: PLOSL1; TREM2-Related Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy; TYROBP-Related Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy
 
Gene (location): TYROBP (19q13.12)
 
Monarch Initiative: MONDO:0020749
OMIM®: 221770

Disease characteristics

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures (resulting from radiologically demonstrable polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages: 1. The latent stage is characterized by normal early development. 2. The osseous stage (3rd decade of life) is 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. In the early neurologic stage (4th decade of life), a change of personality begins to develop insidiously. Affected individuals show a frontal lobe syndrome (loss of judgment, euphoria, loss of social inhibitions, disturbance of concentration, and lack of insight, libido, and motor persistence) leading to serious social issues. 4. The late neurologic stage is characterized by progressive dementia and loss of mobility. Death usually occurs before age 50 years. [from GeneReviews]
Authors:
Juha Paloneva  |  Taina Autti  |  Panu Hakola, et. al.   view full author information

Additional description

From MedlinePlus Genetics
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 the bones of the ankles, feet, wrists, and hands.  Bone pain and fractures are caused by thinning of the bones (osteoporosis) and cysts in the bones.  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.  https://medlineplus.gov/genetics/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Abnormality of the hand
MedGen UID:
6715
Concept ID:
C0018564
Anatomical Abnormality
An abnormality affecting one or both hands.
Abnormal foot morphology
MedGen UID:
1762829
Concept ID:
C5399834
Anatomical Abnormality
An abnormality of the skeleton of foot.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Agnosia
MedGen UID:
174
Concept ID:
C0001816
Mental or Behavioral Dysfunction
Alteration or impairment in the processing or interpretation of sensory information can lead to abnormal perceptions or experiences.
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A defect in the understanding of complex motor commands and in the execution of certain learned movements, i.e., deficits in the cognitive components of learned movements.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Abnormality of speech or vocalization
MedGen UID:
11531
Concept ID:
C0037822
Disease or Syndrome
Abnormalities in the sound of a person's speech or vocalization are not necessarily associated with a known physical cause or due to stuttering or stammering.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Inappropriate behavior
MedGen UID:
66685
Concept ID:
C0233522
Mental or Behavioral Dysfunction
An explicit or perceived action, demonstration, conduct, or language (verbal and written) that is contrary to generally accepted norms, rules, procedures, or unacceptable within the context in which it is carried out. Inappropriate behaviors could take place in a sexual or social context and could be aggressive, violent, impulsive, intimidating, or threatening in nature.
Memory impairment
MedGen UID:
68579
Concept ID:
C0233794
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
Lack of insight
MedGen UID:
65855
Concept ID:
C0233824
Mental or Behavioral Dysfunction
Lack of insight (Anosognosia) is a neurological condition in which an individual is unaware of his or her own neurological deficit or psychiatric condition. Anosognosia can be associated with mental illness, dementia, and structural brain lesions and can affect an indviduals's conscious awareness of deficits involving judgment, emotions, memory, executive function, language skills, and motor ability.
Euphoria
MedGen UID:
115981
Concept ID:
C0235146
Mental Process
Euphoria is a feeling of intense joy, happiness, excitement, or elation that surpasses what would typically be anticipated in a given situation.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Personality changes
MedGen UID:
66817
Concept ID:
C0240735
Mental or Behavioral Dysfunction
An abnormal shift in patterns of thinking, acting, or feeling.
Leukoencephalopathy
MedGen UID:
78722
Concept ID:
C0270612
Disease or Syndrome
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
Frontal lobe dementia
MedGen UID:
572577
Concept ID:
C0338455
Disease or Syndrome
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Disinhibition
MedGen UID:
633911
Concept ID:
C0474398
Finding
Reduced ability to control, or a failure to resist a temptation, urge, or impulse. Examples include disregard for social conventions, general impulsivity, and poor risk assessment.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Peripheral demyelination
MedGen UID:
451074
Concept ID:
C0878575
Pathologic Function
A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
Axonal loss
MedGen UID:
316962
Concept ID:
C1832338
Finding
A reduction in the number of axons in the peripheral nervous system.
Primitive reflex
MedGen UID:
333065
Concept ID:
C1838319
Finding
The primitive reflexes are a group of behavioral motor responses which are found in normal early development, are subsequently inhibited, but may be released from inhibition by cerebral, usually frontal, damage. They are thus part of a broader group of reflexes which reflect release phenomena, such as exaggerated stretch reflexes and extensor plantars. They do however involve more complex motor responses than such simple stretch reflexes, and are often a normal feature in the neonate or infant.
Lateral ventricle dilatation
MedGen UID:
383904
Concept ID:
C1856409
Pathologic Function
Caudate atrophy
MedGen UID:
346745
Concept ID:
C1858116
Disease or Syndrome
Abnormal upper motor neuron morphology
MedGen UID:
871241
Concept ID:
C4025723
Anatomical Abnormality
Any structural anomaly that affects the upper motor neuron.
Bone cyst
MedGen UID:
2696
Concept ID:
C0005937
Anatomical Abnormality
A fluid filled cavity that develops with a bone.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
A pathologic fracture occurs when a bone breaks in an area that is weakened secondarily to another disease process such as tumor, infection, and certain inherited bone disorders. A pathologic fracture can occur without a degree of trauma required to cause fracture in healthy bone.
Basal ganglia calcification
MedGen UID:
234651
Concept ID:
C1389280
Pathologic Function
The presence of calcium deposition affecting one or more structures of the basal ganglia.

Recent clinical studies

Etiology

Kaivola K, Jansson L, Saarentaus E, Kiviharju A, Rantalainen V, Eriksson JG, Strandberg TE, Polvikoski T, Myllykangas L, Tienari PJ
Neurobiol Aging 2018 Apr;64:159.e1-159.e4. Epub 2017 Dec 18 doi: 10.1016/j.neurobiolaging.2017.12.008. PMID: 29336840
Darwent L, Carmona S, Lohmann E, Guven G, Kun-Rodrigues C, Bilgic B, Hanagasi H, Gurvit H, Erginel-Unaltuna N, Pak M, Hardy J, Singleton A, Brás J, Guerreiro R
Neurobiol Aging 2017 Oct;58:240.e1-240.e3. Epub 2017 Jun 28 doi: 10.1016/j.neurobiolaging.2017.06.019. PMID: 28716534Free PMC Article
Walter J
J Biol Chem 2016 Feb 26;291(9):4334-41. Epub 2015 Dec 22 doi: 10.1074/jbc.R115.704981. PMID: 26694609Free PMC Article
Pelham CJ, Pandya AN, Agrawal DK
Expert Opin Ther Pat 2014 Dec;24(12):1383-95. Epub 2014 Nov 1 doi: 10.1517/13543776.2014.977865. PMID: 25363248Free PMC Article
Hakola HP
Dement Geriatr Cogn Disord 1998 Jan-Feb;9(1):39-43. doi: 10.1159/000017020. PMID: 9469264

Diagnosis

Kaivola K, Jansson L, Saarentaus E, Kiviharju A, Rantalainen V, Eriksson JG, Strandberg TE, Polvikoski T, Myllykangas L, Tienari PJ
Neurobiol Aging 2018 Apr;64:159.e1-159.e4. Epub 2017 Dec 18 doi: 10.1016/j.neurobiolaging.2017.12.008. PMID: 29336840
Oyanagi K, Kinoshita M, Suzuki-Kouyama E, Inoue T, Nakahara A, Tokiwai M, Arai N, Satoh JI, Aoki N, Jinnai K, Yazawa I, Arai K, Ishihara K, Kawamura M, Ishizawa K, Hasegawa K, Yagisita S, Amano N, Yoshida K, Terada S, Yoshida M, Akiyama H, Mitsuyama Y, Ikeda SI
Brain Pathol 2017 Nov;27(6):748-769. Epub 2017 Mar 2 doi: 10.1111/bpa.12443. PMID: 27608278Free PMC Article
Bianchin MM, Capella HM, Chaves DL, Steindel M, Grisard EC, Ganev GG, da Silva Júnior JP, Neto Evaldo S, Poffo MA, Walz R, Carlotti Júnior CG, Sakamoto AC
Cell Mol Neurobiol 2004 Feb;24(1):1-24. doi: 10.1023/b:cemn.0000012721.08168.ee. PMID: 15049507
Hakola HP
Dement Geriatr Cogn Disord 1998 Jan-Feb;9(1):39-43. doi: 10.1159/000017020. PMID: 9469264
Mäkelä P, Järví O, Hakola P, Virtama P
Skeletal Radiol 1982;8(1):51-4. doi: 10.1007/BF00361370. PMID: 7079784

Therapy

Hakola HP
Dement Geriatr Cogn Disord 1998 Jan-Feb;9(1):39-43. doi: 10.1159/000017020. PMID: 9469264
Pekkarinen P, Hovatta I, Hakola P, Järvi O, Kestilä M, Lenkkeri U, Adolfsson R, Holmgren G, Nylander PO, Tranebjaerg L, Terwilliger JD, Lönnqvist J, Peltonen L
Am J Hum Genet 1998 Feb;62(2):362-72. doi: 10.1086/301722. PMID: 9463329Free PMC Article

Prognosis

Dash R, Choi HJ, Moon IS
Sci Rep 2020 Feb 27;10(1):3663. doi: 10.1038/s41598-020-60561-x. PMID: 32107424Free PMC Article
Darwent L, Carmona S, Lohmann E, Guven G, Kun-Rodrigues C, Bilgic B, Hanagasi H, Gurvit H, Erginel-Unaltuna N, Pak M, Hardy J, Singleton A, Brás J, Guerreiro R
Neurobiol Aging 2017 Oct;58:240.e1-240.e3. Epub 2017 Jun 28 doi: 10.1016/j.neurobiolaging.2017.06.019. PMID: 28716534Free PMC Article
Chouery E, Delague V, Bergougnoux A, Koussa S, Serre JL, Mégarbané A
Hum Mutat 2008 Sep;29(9):E194-204. doi: 10.1002/humu.20836. PMID: 18546367
Hakola HP
Dement Geriatr Cogn Disord 1998 Jan-Feb;9(1):39-43. doi: 10.1159/000017020. PMID: 9469264

Clinical prediction guides

Dash R, Choi HJ, Moon IS
Sci Rep 2020 Feb 27;10(1):3663. doi: 10.1038/s41598-020-60561-x. PMID: 32107424Free PMC Article
Galimberti D, Fenoglio C, Ghezzi L, Serpente M, Arcaro M, D'Anca M, De Riz M, Arighi A, Fumagalli GG, Pietroboni AM, Piccio L, Scarpini E
Cytokine 2019 Apr;116:115-119. Epub 2019 Jan 25 doi: 10.1016/j.cyto.2018.12.024. PMID: 30690291
Kaivola K, Jansson L, Saarentaus E, Kiviharju A, Rantalainen V, Eriksson JG, Strandberg TE, Polvikoski T, Myllykangas L, Tienari PJ
Neurobiol Aging 2018 Apr;64:159.e1-159.e4. Epub 2017 Dec 18 doi: 10.1016/j.neurobiolaging.2017.12.008. PMID: 29336840
Oyanagi K, Kinoshita M, Suzuki-Kouyama E, Inoue T, Nakahara A, Tokiwai M, Arai N, Satoh JI, Aoki N, Jinnai K, Yazawa I, Arai K, Ishihara K, Kawamura M, Ishizawa K, Hasegawa K, Yagisita S, Amano N, Yoshida K, Terada S, Yoshida M, Akiyama H, Mitsuyama Y, Ikeda SI
Brain Pathol 2017 Nov;27(6):748-769. Epub 2017 Mar 2 doi: 10.1111/bpa.12443. PMID: 27608278Free PMC Article
Hakola HP
Dement Geriatr Cogn Disord 1998 Jan-Feb;9(1):39-43. doi: 10.1159/000017020. PMID: 9469264

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