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Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy(PLOSL)

MedGen UID:
387795
Concept ID:
C1857316
Congenital Abnormality; Disease or Syndrome
Synonyms: Brain-bone-fat disease; Dementia, prefrontal, with bone cysts; Dementia, progressive, with lipomembranous polycystic osteodysplasia; Nasu-Hakola disease; PLOSL; Presenile dementia with bone cysts; TREM2-Related Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy; TYROBP-Related Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: HPO
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
SNOMED CT: Presenile dementia with bone cysts (702347001); PLOSL - polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (702347001); Nasu-Hakola disease (702347001); Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (702347001)
 
Genes (locations): TREM2 (6p21.1); TYROBP (19q13.12)
OMIM®: 221770
Orphanet: ORPHA2770

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 problems. (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 GHR
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.  http://ghr.nlm.nih.gov/condition/polycystic-lipomembranous-osteodysplasia-with-sclerosing-leukoencephalopathy

Clinical features

Acute leukemia
MedGen UID:
43225
Concept ID:
C0085669
Neoplastic Process
A rapidly progressing cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of white blood cells to be produced and enter the blood stream.
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancellation of the vestibulo-ocular reflex.
Acute leukemia
MedGen UID:
43225
Concept ID:
C0085669
Neoplastic Process
A rapidly progressing cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of white blood cells to be produced and enter the blood stream.
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Urinary incontinence (UI) is loss of bladder control. Symptoms can range from mild leaking to uncontrollable wetting. It can happen to anyone, but it becomes more common with age. Women experience UI twice as often as men. Most bladder control problems happen when muscles are too weak or too active. If the muscles that keep your bladder closed are weak, you may have accidents when you sneeze, laugh or lift a heavy object. This is stress incontinence. If bladder muscles become too active, you may feel a strong urge to go to the bathroom when you have little urine in your bladder. This is urge incontinence or overactive bladder. There are other causes of incontinence, such as prostate problems and nerve damage. Treatment depends on the type of problem you have and what best fits your lifestyle. It may include simple exercises, medicines, special devices or procedures prescribed by your doctor, or surgery. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Deformity of foot
MedGen UID:
8888
Concept ID:
C0016506
Anatomical Abnormality
An abnormality of the skeleton of foot.
Abnormality of the hand
MedGen UID:
6715
Concept ID:
C0018564
Anatomical Abnormality
An abnormality affecting one or both hands.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Mental or Behavioral Dysfunction
Aggressive behavior can denote verbal aggression, physical aggression against objects, physical aggression against people, and may also include aggression towards oneself.
Agnosia
MedGen UID:
174
Concept ID:
C0001816
Mental or Behavioral Dysfunction
Inability to recognize objects not because of sensory deficit but because of the inability to combine components of sensory impressions into a complete pattern. Thus, agnosia is a neurological condition which results in an inability to know, to name, to identify, and to extract meaning from visual, auditory, or tactile impressions.
Apraxia
MedGen UID:
8166
Concept ID:
C0003635
Mental or Behavioral Dysfunction
A group of cognitive disorders characterized by the inability to perform previously learned skills that cannot be attributed to deficits of motor or sensory function. The two major subtypes of this condition are ideomotor (see APRAXIA, IDEOMOTOR) and ideational apraxia, which refers to loss of the ability to mentally formulate the processes involved with performing an action. For example, dressing apraxia may result from an inability to mentally formulate the act of placing clothes on the body. Apraxias are generally associated with lesions of the dominant PARIETAL LOBE and supramarginal gyrus. (From Adams et al., Principles of Neurology, 6th ed, pp56-7)
Behavioral Symptoms
MedGen UID:
14048
Concept ID:
C0004941
Sign or Symptom
An abnormality of mental functioning including various affective, behavioural, cognitive and perceptual abnormalities.
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion.
Seizure Disorders
MedGen UID:
4506
Concept ID:
C0014544
Disease or Syndrome
Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells, or neurons, in the brain send out the wrong signals. People may have strange sensations and emotions or behave strangely. They may have violent muscle spasms or lose consciousness. Epilepsy has many possible causes, including illness, brain injury, and abnormal brain development. In many cases, the cause is unknown. Doctors use brain scans and other tests to diagnose epilepsy. It is important to start treatment right away. There is no cure for epilepsy, but medicines can control seizures for most people. When medicines are not working well, surgery or implanted devices such as vagus nerve stimulators may help. Special diets can help some children with epilepsy. NIH: National Institute of Neurological Disorders and Stroke.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
The presence of gliosis in the central nervous system.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Autosomal recessive nonsyndromic hydrocephalus is characterized by onset in utero of enlarged ventricles due to a disturbance of cerebrospinal fluid accumulation. Affected individuals may have neurologic impairment (summary by Drielsma et al., 2012). Hydrocephalus can also be caused by Arnold-Chiari malformation, atresia of foramen of Magendie, stenosis of aqueduct of Sylvius (307000), toxoplasmosis, hydranencephaly, etc. Furthermore, it develops in infancy or childhood in achondroplasia (100800) and in Hurler disease (607014). Genetic Heterogeneity of Congenital Hydrocephalus See also autosomal recessive HYC2 (615219), caused by mutation in the MPDZ gene (603785) on chromosome 9p. An X-linked form (307000) is caused by mutation in the L1CAM gene on (308840) on chromosome Xq28.
Muscle Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Muscle 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
Sign or Symptom
Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some CENTRAL NERVOUS SYSTEM DISEASES; (e.g., EPILEPSY, MYOCLONIC). Nocturnal myoclonus is the principal feature of the NOCTURNAL MYOCLONUS SYNDROME. (From Adams et al., Principles of Neurology, 6th ed, pp102-3).
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
An abnormal reflex consisting of dorsiflexion of the great toe and abduction of the other toes in response to cutaneous stimulation of the plantar surface of the foot.
Neurological speech impairment
MedGen UID:
11531
Concept ID:
C0037822
Disease or Syndrome
A term referring to disorders characterized by the disruption of normal speech. It includes stuttering, lisps, dysarthria and voice disorders.
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.
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
Brain 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
Sign or Symptom
An abnormal shift in patterns of thinking, acting, or feeling.
Leukoencephalopathy
MedGen UID:
78722
Concept ID:
C0270612
Disease or Syndrome
Any of various diseases affecting the white matter of the central nervous system.
Cerebral calcification
MedGen UID:
124360
Concept ID:
C0270685
Finding
The presence of calcium deposition within brain structures.
Frontal lobe dementia
MedGen UID:
572577
Concept ID:
C0338455
Disease or Syndrome
Hypoplasia of corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Disinhibition
MedGen UID:
140859
Concept ID:
C0424296
Mental or Behavioral Dysfunction
A lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment.
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.
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.
Axonal loss
MedGen UID:
316962
Concept ID:
C1832338
Finding
A reduction in the number of axons in the peripheral nervous system.
Developmental regression
MedGen UID:
373115
Concept ID:
C1836550
Finding
Loss of developmental skills, as manifested by loss of developmental milestones.
Primitive reflexes (palmomental, snout, glabellar)
MedGen UID:
333065
Concept ID:
C1838319
Finding
Caudate atrophy
MedGen UID:
346745
Concept ID:
C1858116
Finding
Dilated ventricles (finding)
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Oculomotor apraxia
MedGen UID:
483686
Concept ID:
C3489733
Disease or Syndrome
Ocular motor apraxia is a deficiency in voluntary, horizontal, lateral, fast eye movements (saccades) with retention of slow pursuit movements. The inability to follow objects visually is often compensated by head movements. There may be decreased smooth pursuit, and cancellation of the vestibulo-ocular reflex.
Abnormal upper motor neuron morphology
MedGen UID:
871241
Concept ID:
C4025723
Anatomical Abnormality
Any structural anomaly that affects the upper motor neuron.
Abnormality of the abdominal organs
MedGen UID:
867396
Concept ID:
C4021764
Anatomical Abnormality
An abnormality of the viscera of the abdomen.
Muscle Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Muscle 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.
Acute leukemia
MedGen UID:
43225
Concept ID:
C0085669
Neoplastic Process
A rapidly progressing cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of white blood cells to be produced and enter the blood stream.
Joint pain
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Unicameral bone cyst
MedGen UID:
2696
Concept ID:
C0005937
Anatomical Abnormality
A benign fluid filled simple cyst of bone filled with serous fluid.
Pathologic fracture
MedGen UID:
42095
Concept ID:
C0016663
Pathologic Function
Fractures occurring as a result of disease of a bone or from some undiscoverable cause, and not due to trauma. (Dorland, 27th ed)
Osteochondrodysplasia
MedGen UID:
10495
Concept ID:
C0029422
Congenital Abnormality
A general term describing features characterized by abnormal development of bones and connective tissues.
Bone pain
MedGen UID:
57489
Concept ID:
C0151825
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.
Cerebral calcification
MedGen UID:
124360
Concept ID:
C0270685
Finding
The presence of calcium deposition within brain structures.
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.
Decreased joint mobility
MedGen UID:
341696
Concept ID:
C1857108
Finding
A reduction in the freedom of movement of one or more joints.
Reduced bone mineral density
MedGen UID:
393152
Concept ID:
C2674432
Finding
A reduction of bone mineral density, that is, of the amount of matter per cubic centimeter of bones.
Abnormality of epiphysis morphology
MedGen UID:
867251
Concept ID:
C4021611
Anatomical Abnormality
An anomaly of epiphysis, which is the expanded articular end of a long bone that developes from a secondary ossification center, and which during the period of growth is either entirely cartilaginous or is separated from the shaft by a cartilaginous disk.
Abnormality of adipose tissue
MedGen UID:
867166
Concept ID:
C4021524
Anatomical Abnormality
An abnormality of adipose tissue, which is loose connective tissue composed of adipocytes.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPolycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy
Follow this link to review classifications for Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy in Orphanet.

Recent clinical studies

Etiology

Park JS, Ji IJ, An HJ, Kang MJ, Kang SW, Kim DH, Yoon SY
Traffic 2015 May;16(5):510-8. Epub 2015 Feb 24 doi: 10.1111/tra.12264. [Epub ahead of print] PMID: 25615530
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. [Epub ahead of print] PMID: 25363248Free PMC Article
Nwawka OK, Schneider R, Bansal M, Mintz DN, Lane J
Skeletal Radiol 2014 Oct;43(10):1449-55. Epub 2014 Apr 29 doi: 10.1007/s00256-014-1887-5. [Epub ahead of print] PMID: 24777445
Giraldo M, Lopera F, Siniard AL, Corneveaux JJ, Schrauwen I, Carvajal J, Muñoz C, Ramirez-Restrepo M, Gaiteri C, Myers AJ, Caselli RJ, Kosik KS, Reiman EM, Huentelman MJ
Neurobiol Aging 2013 Aug;34(8):2077.e11-8. Epub 2013 Apr 9 doi: 10.1016/j.neurobiolaging.2013.02.016. [Epub ahead of print] PMID: 23582655Free PMC Article
Guerreiro RJ, Lohmann E, Brás JM, Gibbs JR, Rohrer JD, Gurunlian N, Dursun B, Bilgic B, Hanagasi H, Gurvit H, Emre M, Singleton A, Hardy J
JAMA Neurol 2013 Jan;70(1):78-84. doi: 10.1001/jamaneurol.2013.579. PMID: 23318515Free PMC Article

Diagnosis

Sahebari M, Abbasi B, Akhondpour Manteghi A, Abdollahi N
J Clin Rheumatol 2014 Apr;20(3):160-2. doi: 10.1097/RHU.0000000000000097. PMID: 24662559
Bock V, Botturi A, Gaviani P, Lamperti E, Maccagnano C, Piccio L, Silvani A, Salmaggi A
J Neurol Sci 2013 Mar 15;326(1-2):115-9. Epub 2013 Feb 9 doi: 10.1016/j.jns.2013.01.021. [Epub ahead of print] PMID: 23399524
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. PMID: 15049507
Hakola HP, Puranen M
Acta Neurol Scand 1993 Nov;88(5):370-5. PMID: 8296538
Iivanainen M, Hakola P, Erkinjuntti T, Sipponen JT, Ketonen L, Sulkava R, Sepponen RE
J Comput Assist Tomogr 1984 Oct;8(5):940-3. PMID: 6470263

Therapy

Hakola HP
Dement Geriatr Cogn Disord 1998 Jan-Feb;9(1):39-43. 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

Nwawka OK, Schneider R, Bansal M, Mintz DN, Lane J
Skeletal Radiol 2014 Oct;43(10):1449-55. Epub 2014 Apr 29 doi: 10.1007/s00256-014-1887-5. [Epub ahead of print] PMID: 24777445
Solje E, Hartikainen P, Valori M, Vanninen R, Tiihonen J, Hakola P, Tienari PJ, Remes AM
Neurobiol Aging 2014 Jul;35(7):1780.e13-7. Epub 2014 Feb 5 doi: 10.1016/j.neurobiolaging.2014.01.149. [Epub ahead of print] PMID: 24612676
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
Madry H, Prudlo J, Grgic A, Freyschmidt J
Clin Orthop Relat Res 2007 Jan;454:262-9. doi: 10.1097/01.blo.0000229364.57985.df. PMID: 16906106
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
Neurology 2005 May 10;64(9):1502-7. doi: 10.1212/01.WNL.0000160304.00003.CA. PMID: 15883308

Clinical prediction guides

La Piana R, Webber A, Guiot MC, Del Pilar Cortes M, Brais B
Neurogenetics 2014 Oct;15(4):289-94. Epub 2014 Jul 12 doi: 10.1007/s10048-014-0413-1. [Epub ahead of print] PMID: 25012610
Ohgidani M, Kato TA, Setoyama D, Sagata N, Hashimoto R, Shigenobu K, Yoshida T, Hayakawa K, Shimokawa N, Miura D, Utsumi H, Kanba S
Sci Rep 2014 May 14;4:4957. doi: 10.1038/srep04957. PMID: 24825127Free PMC Article
Solje E, Hartikainen P, Valori M, Vanninen R, Tiihonen J, Hakola P, Tienari PJ, Remes AM
Neurobiol Aging 2014 Jul;35(7):1780.e13-7. Epub 2014 Feb 5 doi: 10.1016/j.neurobiolaging.2014.01.149. [Epub ahead of print] PMID: 24612676
Hakola HP, Puranen M
Acta Neurol Scand 1993 Nov;88(5):370-5. PMID: 8296538
Iivanainen M, Hakola P, Erkinjuntti T, Sipponen JT, Ketonen L, Sulkava R, Sepponen RE
J Comput Assist Tomogr 1984 Oct;8(5):940-3. PMID: 6470263

Recent systematic reviews

Montalbetti L, Soragna D, Ratti MT, Bini P, Buscone S, Moglia A
Funct Neurol 2004 Jul-Sep;19(3):171-9. PMID: 15595711

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