U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Megalencephalic leukoencephalopathy with subcortical cysts 3(MLC3)

MedGen UID:
1841261
Concept ID:
C5830625
Disease or Syndrome
Synonym: MLC3
 
Gene (location): GPRC5B (16p12.3)
 
Monarch Initiative: MONDO:0957533
OMIM®: 620447

Definition

Megalencephalic leukoencephalopathy with subcortical cysts-3 (MLC3) is a neurodegenerative disorder characterized by increased head circumference in infancy followed by progressive motor and cognitive decline in early childhood. Affected individuals either do not achieve walking or lose independent ambulation in the first or second decades. Cognitive impairment is variable and accompanied by poor speech and dysarthria. Most patients have early-onset seizures, which may be mild or refractory. Brain imaging shows unremitting megalencephalic leukoencephalopathy with subcortical cysts and swelling of the cerebral white matter (Passchier et al., 2023). For a discussion of genetic heterogeneity of megalencephalic leukoencephalopathy with subcortical cysts, see MLC1 (604004). [from OMIM]

Clinical features

From HPO
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
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.
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.
Clumsiness
MedGen UID:
66690
Concept ID:
C0233844
Sign or Symptom
Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
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.
Limb ataxia
MedGen UID:
196692
Concept ID:
C0750937
Finding
A kind of ataxia that affects movements of the extremities.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis
Upper limb spasticity
MedGen UID:
220882
Concept ID:
C1273957
Finding
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Motor deterioration
MedGen UID:
356495
Concept ID:
C1866284
Finding
Loss of previously present motor (i.e., movement) abilities.
Cerebral subcortical cyst
MedGen UID:
1054415
Concept ID:
CN377293
Finding
A fluid-filled sac (cyst) in the region below the cortex of the cerebrum. In magnetic resonance imaging, the fluid within the cyst has the same appearance as cerebrospinal fluid (CSF).
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.

Professional guidelines

PubMed

DiBardino DM, Saqi A, Elvin JA, Greenbowe J, Suh JH, Miller VA, Ali SM, Stoopler M, Bulman WA
Clin Lung Cancer 2016 Nov;17(6):517-522.e3. Epub 2016 Jun 8 doi: 10.1016/j.cllc.2016.05.017. PMID: 27378171

Recent clinical studies

Etiology

Zhang J, Ban T, Zhou L, Ji H, Yan H, Shi Z, Cao B, Jiang Y, Wang J, Wu Y
J Neurol 2020 Sep;267(9):2612-2618. Epub 2020 May 9 doi: 10.1007/s00415-020-09889-y. PMID: 32388833
Jia X, Madireddy L, Caillier S, Santaniello A, Esposito F, Comi G, Stuve O, Zhou Y, Taylor B, Kilpatrick T, Martinelli-Boneschi F, Cree BAC, Oksenberg JR, Hauser SL, Baranzini SE
Ann Neurol 2018 Jul;84(1):51-63. Epub 2018 Jul 3 doi: 10.1002/ana.25263. PMID: 29908077Free PMC Article
Wang J, Shang J, Wu Y, Gu Q, Xiong H, Ding C, Wang L, Gao Z, Wu X, Jiang Y
J Hum Genet 2011 Feb;56(2):138-42. Epub 2010 Dec 16 doi: 10.1038/jhg.2010.146. PMID: 21160490
van der Knaap MS, Lai V, Köhler W, Salih MA, Fonseca MJ, Benke TA, Wilson C, Jayakar P, Aine MR, Dom L, Lynch B, Kálmánchey R, Pietsch P, Errami A, Scheper GC
Ann Neurol 2010 Jun;67(6):834-7. doi: 10.1002/ana.21980. PMID: 20517947
Topçu M, Gartioux C, Ribierre F, Yalçinkaya C, Tokus E, Oztekin N, Beckmann JS, Ozguc M, Seboun E
Am J Hum Genet 2000 Feb;66(2):733-9. doi: 10.1086/302758. PMID: 10677334Free PMC Article

Diagnosis

Bravo-Oro A, Reyes-Vaca JG, Noriega-Reyes MF, Esmer C
Bol Med Hosp Infant Mex 2022;79(2):129-134. doi: 10.24875/BMHIM.21000069. PMID: 35468122
Amin M, Vignal C, Hamed AAA, Mohammed IN, Elseed MA, Drunat S, Babai A, Eltaraifee E, Elbadi I, Abubaker R, Mustafa D, Yahia A, Koko M, Osman M, Bakhit Y, Elshafea A, Alsiddig M, Haroun S, Lelay G, Elsayed LEO, Ahmed AE, Boespflug-Tanguy O, Dorboz I
J Hum Genet 2022 Mar;67(3):127-132. Epub 2021 Sep 10 doi: 10.1038/s10038-021-00945-7. PMID: 34504271
Zhang J, Ban T, Zhou L, Ji H, Yan H, Shi Z, Cao B, Jiang Y, Wang J, Wu Y
J Neurol 2020 Sep;267(9):2612-2618. Epub 2020 May 9 doi: 10.1007/s00415-020-09889-y. PMID: 32388833
Dubey M, Brouwers E, Hamilton EMC, Stiedl O, Bugiani M, Koch H, Kole MHP, Boschert U, Wykes RC, Mansvelder HD, van der Knaap MS, Min R
Ann Neurol 2018 Mar;83(3):636-649. Epub 2018 Mar 13 doi: 10.1002/ana.25190. PMID: 29466841Free PMC Article
Petrini S, Minnone G, Coccetti M, Frank C, Aiello C, Cutarelli A, Ambrosini E, Lanciotti A, Brignone MS, D'Oria V, Strippoli R, De Benedetti F, Bertini E, Bracci-Laudiero L
Mol Cell Neurosci 2013 Sep;56:307-21. Epub 2013 Jul 10 doi: 10.1016/j.mcn.2013.07.001. PMID: 23851226

Prognosis

Bravo-Oro A, Reyes-Vaca JG, Noriega-Reyes MF, Esmer C
Bol Med Hosp Infant Mex 2022;79(2):129-134. doi: 10.24875/BMHIM.21000069. PMID: 35468122
Shi Z, Yan HF, Cao BB, Guo MM, Xie H, Gao K, Xiao JX, Yang YL, Xiong H, Gu Q, Li M, Wu Y, Jiang YW, Wang JM
World J Pediatr 2019 Oct;15(5):454-464. Epub 2019 Aug 1 doi: 10.1007/s12519-019-00284-w. PMID: 31372844Free PMC Article
Jia X, Madireddy L, Caillier S, Santaniello A, Esposito F, Comi G, Stuve O, Zhou Y, Taylor B, Kilpatrick T, Martinelli-Boneschi F, Cree BAC, Oksenberg JR, Hauser SL, Baranzini SE
Ann Neurol 2018 Jul;84(1):51-63. Epub 2018 Jul 3 doi: 10.1002/ana.25263. PMID: 29908077Free PMC Article
van der Knaap MS, Lai V, Köhler W, Salih MA, Fonseca MJ, Benke TA, Wilson C, Jayakar P, Aine MR, Dom L, Lynch B, Kálmánchey R, Pietsch P, Errami A, Scheper GC
Ann Neurol 2010 Jun;67(6):834-7. doi: 10.1002/ana.21980. PMID: 20517947
Riel-Romero RM, Smith CD, Pettigrew AL
J Child Neurol 2005 Mar;20(3):230-4. doi: 10.1177/088307380502000301. PMID: 15832614

Clinical prediction guides

Ain Ul Batool S, Almatrafi A, Fadhli F, Alluqmani M, Sadia, Ali G, Basit S
Am J Med Genet A 2022 Apr;188(4):1075-1082. Epub 2021 Dec 17 doi: 10.1002/ajmg.a.62614. PMID: 34918859
Zhang J, Ban T, Zhou L, Ji H, Yan H, Shi Z, Cao B, Jiang Y, Wang J, Wu Y
J Neurol 2020 Sep;267(9):2612-2618. Epub 2020 May 9 doi: 10.1007/s00415-020-09889-y. PMID: 32388833
Petrini S, Minnone G, Coccetti M, Frank C, Aiello C, Cutarelli A, Ambrosini E, Lanciotti A, Brignone MS, D'Oria V, Strippoli R, De Benedetti F, Bertini E, Bracci-Laudiero L
Mol Cell Neurosci 2013 Sep;56:307-21. Epub 2013 Jul 10 doi: 10.1016/j.mcn.2013.07.001. PMID: 23851226
Montagna G, Teijido O, Eymard-Pierre E, Muraki K, Cohen B, Loizzo A, Grosso P, Tedeschi G, Palacín M, Boespflug-Tanguy O, Bertini E, Santorelli FM, Estévez R
Hum Mutat 2006 Mar;27(3):292. doi: 10.1002/humu.9407. PMID: 16470554
Topçu M, Gartioux C, Ribierre F, Yalçinkaya C, Tokus E, Oztekin N, Beckmann JS, Ozguc M, Seboun E
Am J Hum Genet 2000 Feb;66(2):733-9. doi: 10.1086/302758. PMID: 10677334Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Consumer resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...