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Leukoencephalopathy with calcifications and cysts(LCC)

MedGen UID:
482830
Concept ID:
C3281200
Disease or Syndrome
Synonyms: LABRUNE SYNDROME; Leukoencephalopathy, brain calcifications, and cysts
SNOMED CT: Leukoencephalopathy with calcifications and cysts (1186710001); Labrune syndrome (1186710001)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SNORD118 (17p13.1)
 
Monarch Initiative: MONDO:0013803
OMIM®: 614561
Orphanet: ORPHA542310

Definition

Leukoencephalopathy, brain calcifications, and cysts (LCC), also known as Labrune syndrome, is characterized by a constellation of features restricted to the central nervous system, including leukoencephalopathy, brain calcifications, and cysts, resulting in spasticity, dystonia, seizures, and cognitive decline (summary by Labrune et al., 1996). See also cerebroretinal microangiopathy with calcifications and cysts (CRMCC; 612199), an autosomal recessive disorder caused by mutation in the CTC1 gene (613129) that shows phenotypic similarities to Labrune syndrome. CRMCC includes the neurologic findings of intracranial calcifications, leukodystrophy, and brain cysts, but also includes retinal vascular abnormalities and other systemic manifestations, such as osteopenia with poor bone healing, a high risk of gastrointestinal bleeding, hair, skin, and nail changes, and anemia and thrombocytopenia. Although Coats plus syndrome and Labrune syndrome were initially thought to be manifestations of the same disorder, namely CRMCC, molecular evidence has excluded mutations in the CTC1 gene in patients with Labrune syndrome, suggesting that the 2 disorders are not allelic (Anderson et al., 2012; Polvi et al., 2012). [from OMIM]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Hemiplegia
MedGen UID:
9196
Concept ID:
C0018991
Sign or Symptom
Paralysis (complete loss of muscle function) in the arm, leg, and in some cases the face on one side of the body.
Leukodystrophy
MedGen UID:
6070
Concept ID:
C0023520
Disease or Syndrome
Leukodystrophy refers to deterioration of white matter of the brain resulting from degeneration of myelin sheaths in the CNS. Their basic defect is directly related to the synthesis and maintenance of myelin membranes. Symmetric white matter involvement at MRI is a typical finding in patients with leukodystrophies.
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.
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.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Abnormal pyramidal sign
MedGen UID:
68582
Concept ID:
C0234132
Sign or Symptom
Functional neurological abnormalities related to dysfunction of the pyramidal tract.
Abnormality of extrapyramidal motor function
MedGen UID:
115941
Concept ID:
C0234133
Sign or Symptom
A neurological condition related to lesions of the basal ganglia leading to typical abnormalities including akinesia (inability to initiate changes in activity and perform volitional movements rapidly and easily), muscular rigidity (continuous contraction of muscles with constant resistance to passive movement), chorea (widespread arrhythmic movements of a forcible, rapid, jerky, and restless nature), athetosis (inability to sustain the muscles of the fingers, toes, or other group of muscles in a fixed position), and akathisia (inability to remain motionless).
Mental deterioration
MedGen UID:
66713
Concept ID:
C0234985
Mental or Behavioral Dysfunction
Loss of previously present mental abilities, generally in adults.
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.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Cerebral calcification
MedGen UID:
124360
Concept ID:
C0270685
Finding
The presence of calcium deposition within the cerebrum.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLeukoencephalopathy with calcifications and cysts

Recent clinical studies

Etiology

Lomidze G, Chutkerashvili G, Tskhvaradze S, Gzirishvili N, Kasradze S
Epileptic Disord 2022 Dec 1;24(6):1110-1115. doi: 10.1684/epd.2022.1478. PMID: 35942509
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Jenkinson EM, Rodero MP, Kasher PR, Uggenti C, Oojageer A, Goosey LC, Rose Y, Kershaw CJ, Urquhart JE, Williams SG, Bhaskar SS, O'Sullivan J, Baerlocher GM, Haubitz M, Aubert G, Barañano KW, Barnicoat AJ, Battini R, Berger A, Blair EM, Brunstrom-Hernandez JE, Buckard JA, Cassiman DM, Caumes R, Cordelli DM, De Waele LM, Fay AJ, Ferreira P, Fletcher NA, Fryer AE, Goel H, Hemingway CA, Henneke M, Hughes I, Jefferson RJ, Kumar R, Lagae L, Landrieu PG, Lourenço CM, Malpas TJ, Mehta SG, Metz I, Naidu S, Õunap K, Panzer A, Prabhakar P, Quaghebeur G, Schiffmann R, Sherr EH, Sinnathuray KR, Soh C, Stewart HS, Stone J, Van Esch H, Van Mol CE, Vanderver A, Wakeling EL, Whitney A, Pavitt GD, Griffiths-Jones S, Rice GI, Revy P, van der Knaap MS, Livingston JH, O'Keefe RT, Crow YJ
Nat Genet 2016 Oct;48(10):1185-92. Epub 2016 Aug 29 doi: 10.1038/ng.3661. PMID: 27571260Free PMC Article
Bartolini E, Bianchi A, Bartolomei I, Vella A, Sali L, Ciccarone A, Salvi F, Mascalchi M
J Stroke Cerebrovasc Dis 2016 Aug;25(8):e111-3. Epub 2016 May 19 doi: 10.1016/j.jstrokecerebrovasdis.2016.04.030. PMID: 27212271

Diagnosis

Livingston JH
Handb Clin Neurol 2024;204:95-109. doi: 10.1016/B978-0-323-99209-1.00013-2. PMID: 39322397
Li J, Li C, Zhang Q, Qiu C
Neurol Sci 2023 Aug;44(8):2715-2729. Epub 2023 Apr 1 doi: 10.1007/s10072-023-06776-y. PMID: 37004603
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Osman O, Labrune P, Reiner P, Sarov M, Nasser G, Riant F, Tournier-Lasserve E, Chabriat H, Denier C
Rev Neurol (Paris) 2020 Mar;176(3):170-179. Epub 2019 Sep 11 doi: 10.1016/j.neurol.2019.06.006. PMID: 31521395
Karlinger K, Tárnoki ÁD, Tárnoki DL, Polvi A, Lehesjoki AE, Kelemen A, Szegedi L, Turányi E, Kamondi A, Szűcs A
J Neurol 2014 Oct;261(10):1911-6. Epub 2014 Jul 18 doi: 10.1007/s00415-014-7393-9. PMID: 25034270

Therapy

Beerepoot S, Ardon H, Niers A, van der Knaap MS
Clin Neurol Neurosurg 2024 Oct;245:108517. Epub 2024 Aug 18 doi: 10.1016/j.clineuro.2024.108517. PMID: 39173493
Helman G, Viaene AN, Takanohashi A, Breur M, Berger R, Woidill S, Cottrell JR, Schiffmann R, Crow YJ, Simons C, Bugiani M, Vanderver A
J Child Neurol 2021 Feb;36(2):133-140. Epub 2020 Sep 28 doi: 10.1177/0883073820958330. PMID: 32988269
Fay AJ, King AA, Shimony JS, Crow YJ, Brunstrom-Hernandez JE
Pediatr Neurol 2017 Jun;71:56-59. Epub 2017 Mar 23 doi: 10.1016/j.pediatrneurol.2017.03.008. PMID: 28424147Free PMC Article
Stephani C, Pfeifenbring S, Mohr A, Stadelmann C
BMC Neurol 2016 Feb 6;16:19. doi: 10.1186/s12883-016-0543-1. PMID: 26852234Free PMC Article

Prognosis

Novegno F, Iaquinandi A, Ruggiero F, Salvati M
World Neurosurg 2024 Oct;190:99-112. Epub 2024 Jul 3 doi: 10.1016/j.wneu.2024.06.133. PMID: 38968992
Lomidze G, Chutkerashvili G, Tskhvaradze S, Gzirishvili N, Kasradze S
Epileptic Disord 2022 Dec 1;24(6):1110-1115. doi: 10.1684/epd.2022.1478. PMID: 35942509
Helman G, Viaene AN, Takanohashi A, Breur M, Berger R, Woidill S, Cottrell JR, Schiffmann R, Crow YJ, Simons C, Bugiani M, Vanderver A
J Child Neurol 2021 Feb;36(2):133-140. Epub 2020 Sep 28 doi: 10.1177/0883073820958330. PMID: 32988269
Osman O, Labrune P, Reiner P, Sarov M, Nasser G, Riant F, Tournier-Lasserve E, Chabriat H, Denier C
Rev Neurol (Paris) 2020 Mar;176(3):170-179. Epub 2019 Sep 11 doi: 10.1016/j.neurol.2019.06.006. PMID: 31521395
Li Z, Han K, Yao W, Wei W, Li Y, Lan X
World Neurosurg 2016 Jan;85:366.e9-13. Epub 2015 Sep 25 doi: 10.1016/j.wneu.2015.09.049. PMID: 26407930

Clinical prediction guides

Della Vecchia S, Tessa A, Pasquariello R, Seabra L, Crow YJ, Battini R
Int J Mol Sci 2024 Mar 1;25(5) doi: 10.3390/ijms25052864. PMID: 38474113Free PMC Article
Crow YJ, Marshall H, Rice GI, Seabra L, Jenkinson EM, Baranano K, Battini R, Berger A, Blair E, Blauwblomme T, Bolduc F, Boddaert N, Buckard J, Burnett H, Calvert S, Caumes R, Ng AC, Chiang D, Clifford DB, Cordelli DM, de Burca A, Demic N, Desguerre I, De Waele L, Di Fonzo A, Dunham SR, Dyack S, Elmslie F, Ferrand M, Fisher G, Karimiani EG, Ghoumid J, Gibbon F, Goel H, Hilmarsen HT, Hughes I, Jacob A, Jones EA, Kumar R, Leventer RJ, MacDonald S, Maroofian R, Mehta SG, Metz I, Monfrini E, Neumann D, Noetzel M, O'Driscoll M, Õunap K, Panzer A, Parikh S, Prabhakar P, Ramond F, Sandford R, Saneto R, Soh C, Stutterd CA, Subramanian GM, Talbot K, Thomas RH, Toro C, Touraine R, Wakeling E, Wassmer E, Whitney A, Livingston JH, O'Keefe RT, Badrock AP
Am J Med Genet A 2021 Jan;185(1):15-25. Epub 2020 Oct 7 doi: 10.1002/ajmg.a.61907. PMID: 33029936
Osman O, Labrune P, Reiner P, Sarov M, Nasser G, Riant F, Tournier-Lasserve E, Chabriat H, Denier C
Rev Neurol (Paris) 2020 Mar;176(3):170-179. Epub 2019 Sep 11 doi: 10.1016/j.neurol.2019.06.006. PMID: 31521395
Fay AJ, King AA, Shimony JS, Crow YJ, Brunstrom-Hernandez JE
Pediatr Neurol 2017 Jun;71:56-59. Epub 2017 Mar 23 doi: 10.1016/j.pediatrneurol.2017.03.008. PMID: 28424147Free PMC Article
Renard D, Brochet B, Vukusic S, Edan G, Deburghgraeve V, Goizet C, Dupuy D, Touze E, Deschamps R, Zephyr H, Creange A, Castelnovo G, Boespflug-Tanguy O, Labauge P
Eur Neurol 2012;68(3):156-61. Epub 2012 Aug 14 doi: 10.1159/000338476. PMID: 22907640

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