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Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy(PLOSL)

MedGen UID:
387795
Concept ID:
C1857316
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
Autosomal recessive inheritance refers to genetic conditions that occur only when mutations are present in both copies of a given gene (i.e., the person is homozygous for a mutation, or carries two different mutations of the same gene, a state referred to as compound heterozygosity).
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

Definition

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.
[from GHR]

Clinical features

Acute leukemia
MedGen UID:
505251
Concept ID:
CN002259
Finding
Urinary incontinence
MedGen UID:
776587
Concept ID:
C2712331
Finding
Oculomotor apraxia
MedGen UID:
504541
Concept ID:
CN000618
Finding
Inability to follow objects visually with compensatory head movements, decreased smooth pursuit, and cancellation of the vestibulo-ocular reflex.
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.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Hypertonia
MedGen UID:
115988
Concept ID:
C0235396
Finding
Cerebral calcification
MedGen UID:
124360
Concept ID:
C0270685
Finding
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Sign or Symptom
A finding referring to walking difficulties.
Axonal loss
MedGen UID:
316962
Concept ID:
C1832338
Finding
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Frontal lobe dementia
MedGen UID:
337641
Concept ID:
C1846712
Finding
Hypoplasia of the corpus callosum
MedGen UID:
342925
Concept ID:
C1853617
Finding
Caudate atrophy
MedGen UID:
346745
Concept ID:
C1858116
Finding
Seizures
MedGen UID:
409523
Concept ID:
C1959629
Finding
Hydrocephalus
MedGen UID:
369747
Concept ID:
C1963137
Finding
Memory impairment
MedGen UID:
368424
Concept ID:
C1963167
Finding
Oculomotor apraxia
MedGen UID:
504541
Concept ID:
CN000618
Finding
Inability to follow objects visually with compensatory head movements, decreased smooth pursuit, and cancellation of the vestibulo-ocular reflex.
Behavioral abnormality
MedGen UID:
425007
Concept ID:
CN000665
Finding
An abnormality of mental functioning including various affective, behavioural, cognitive and perceptual abnormalities.
Aggressive behavior
MedGen UID:
504570
Concept ID:
CN000675
Finding
Aggressive behavior can denote verbal aggression, physical aggression against objects, physical aggression against people, and may also include aggression towards oneself.
Disinhibition
MedGen UID:
504576
Concept ID:
CN000690
Finding
A lack of restraint manifested in several ways, including disregard for social conventions, impulsivity, and poor risk assessment.
Personality changes
MedGen UID:
504584
Concept ID:
CN000707
Finding
An abnormal shift in patterns of thinking, acting, or feeling.
Lack of insight
MedGen UID:
504587
Concept ID:
CN000711
Finding
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Myoclonus
MedGen UID:
504806
Concept ID:
CN001224
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Cerebral atrophy
MedGen UID:
505074
Concept ID:
CN001862
Finding
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Chorea
MedGen UID:
505081
Concept ID:
CN001874
Finding
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion.
Ventriculomegaly
MedGen UID:
505112
Concept ID:
CN001919
Finding
An increase in size of the ventricular system of the brain.
Cerebral cortical atrophy
MedGen UID:
505113
Concept ID:
CN001920
Finding
Atrophy of the cortex of the cerebrum.
Abnormal upper motor neuron morphology
MedGen UID:
446436
Concept ID:
CN001927
Finding
Any structural anomaly that affects the upper motor neuron.
Basal ganglia calcification
MedGen UID:
505119
Concept ID:
CN001935
Finding
The presence of calcium deposition affecting one or more structures of the basal ganglia.
Neurological speech impairment
MedGen UID:
446437
Concept ID:
CN001964
Finding
Gliosis
MedGen UID:
505139
Concept ID:
CN001968
Finding
The presence of gliosis in the central nervous system.
Apraxia
MedGen UID:
505148
Concept ID:
CN001982
Finding
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.
Leukoencephalopathy
MedGen UID:
505209
Concept ID:
CN002135
Finding
This term describes abnormality of the white matter of the cerebrum resulting from damage to the myelin sheaths of nerve cells.
Primitive reflexes (palmomental, snout, glabellar)
MedGen UID:
505248
Concept ID:
CN002249
Finding
Agnosia
MedGen UID:
506372
Concept ID:
CN009355
Finding
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.
Peripheral demyelination
MedGen UID:
506437
Concept ID:
CN116827
Finding
A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
Cerebral calcification
MedGen UID:
124360
Concept ID:
C0270685
Finding
Arthralgia
MedGen UID:
409545
Concept ID:
C1963066
Finding
Bone pain
MedGen UID:
368783
Concept ID:
C1963077
Finding
Reduced bone mineral density
MedGen UID:
393152
Concept ID:
C2674432
Finding
Limitation of joint mobility
MedGen UID:
446405
Concept ID:
CN001260
Finding
A reduction in the freedom of movement of one or more joints.
Basal ganglia calcification
MedGen UID:
505119
Concept ID:
CN001935
Finding
The presence of calcium deposition affecting one or more structures of the basal ganglia.
Skeletal dysplasia
MedGen UID:
505316
Concept ID:
CN002411
Finding
A general term describing features characterized by abnormal development of bones and connective tissues.
Pathologic fracture
MedGen UID:
505347
Concept ID:
CN002501
Finding
A pathologic fracture occurs when a bone breaks in an area that is weakened secondary 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.
Abnormality of epiphysis morphology
MedGen UID:
425804
Concept ID:
CN005226
Finding
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.
Bone cyst
MedGen UID:
506659
Concept ID:
CN167788
Finding
A fluid filled cavity that develops with a bone.
Abnormality of the abdominal organs
MedGen UID:
428289
Concept ID:
CN001821
Finding
An abnormality of the viscera of the abdomen.
Acute leukemia
MedGen UID:
505251
Concept ID:
CN002259
Finding
Acute leukemia
MedGen UID:
505251
Concept ID:
CN002259
Finding
Hypertonia
MedGen UID:
115988
Concept ID:
C0235396
Finding
Spasticity
MedGen UID:
504771
Concept ID:
CN001152
Finding
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Abnormality of adipose tissue
MedGen UID:
428873
Concept ID:
CN008014
Finding
An abnormality of adipose tissue20110), which is loose connective tissue composed of adipocytes.
Abnormality of the hand
MedGen UID:
427857
Concept ID:
CN001087
Finding
An abnormality affecting one or both hands.
Abnormality of the foot
MedGen UID:
427893
Concept ID:
CN001600
Finding
An abnormality of the skeleton of foot.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews
  • CROGPolycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy

Recent clinical studies

Etiology

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
Nakamagoe K, Shioya A, Yamaguchi T, Takahashi H, Koide R, Monzen T, Satoh J, Tamaoka A
Intern Med 2011;50(22):2839-44. Epub 2011 Nov 15 PMID: 22082900
Numasawa Y, Yamaura C, Ishihara S, Shintani S, Yamazaki M, Tabunoki H, Satoh JI
Eur J Neurol 2011 Sep;18(9):1179-83. Epub 2010 Dec 22 doi: 10.1111/j.1468-1331.2010.03311.x. [Epub ahead of print] PMID: 21834902

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
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
Satoh J, Tabunoki H, Ishida T, Yagishita S, Jinnai K, Futamura N, Kobayashi M, Toyoshima I, Yoshioka T, Enomoto K, Arai N, Saito Y, Arima K
Neuropathology 2012 Apr;32(2):149-57. Epub 2011 Oct 10 doi: 10.1111/j.1440-1789.2011.01256.x. [Epub ahead of print] PMID: 21981270
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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