Megalencephalic leukoencephalopathy with subcortical cysts

A heriditary autosomal recessive leukodystrophy characterized by early-onset MEGALENCEPHALY and delayed-onset neurologic deterioration, including CEREBELLAR ATAXIA; MUSCLE SPASTICITY; EPILEPSY, and mild DEMENTIA. Mutations in the MLC1 gene have been identified. OMIM: 604004

Also Known As:

Infantile Leukoencephalopathy and Megalencephaly; Leukoencephalopathy with Swelling and A Discrepantly Mild Course; Leukoencephalopathy with swelling and cysts; Megalencephaly-cystic leukodystrophy; Vacuolating Leukoencephalopathy; Vacuolating megalencephalic leukoencephalopathy with subcortical cysts; Van Der Knapp Disease

Networked: 33 relevant articles (0 outcomes, 0 trials/studies)

Disease Context: Research Results

Related Diseases

1.	Megalencephaly
2.	Leukoencephalopathies
3.	Alexander Disease (Alexander's Disease)
4.	Neuronal Ceroid-Lipofuscinoses (Neuronal Ceroid Lipofuscinosis)
5.	Cysts

Experts

1.	Ambrosini, Elena: 7 articles (01/2020 - 03/2010)
2.	Lanciotti, Angela: 7 articles (01/2020 - 03/2010)
3.	Brignone, Maria Stefania: 5 articles (01/2020 - 03/2010)
4.	Molinari, Paola: 5 articles (01/2020 - 03/2010)
5.	Bertini, Enrico: 5 articles (04/2016 - 05/2012)
6.	Estévez, Raúl: 4 articles (05/2022 - 11/2004)
7.	Petrucci, Tamara Corinna: 4 articles (01/2020 - 03/2010)
8.	Visentin, Sergio: 4 articles (01/2020 - 05/2012)
9.	McCarty, Joseph H: 3 articles (01/2022 - 10/2017)
10.	Mallozzi, Cinzia: 3 articles (01/2020 - 04/2016)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Megalencephalic leukoencephalopathy with subcortical cysts:

1.	Proteins (Proteins, Gene)FDA Link 05/16/2022 - "Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare type of vacuolating leukodystrophy (white matter disorder), which is mainly caused by defects in MLC1 or glial cell adhesion molecule (GlialCAM) proteins. " 12/01/2020 - "Here, we have analyzed functions for megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1), an eight-transmembrane protein normally expressed in perivascular brain astrocyte end feet that is essential for neurovascular development and physiology, in the pathogenesis of GBM. " 01/01/2018 - "Loss of function of the astrocyte-specific protein MLC1 leads to the childhood-onset leukodystrophy "megalencephalic leukoencephalopathy with subcortical cysts" (MLC). " 10/01/2017 - "Megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1) is a transmembrane protein that is expressed in perivascular astrocyte end feet where it controls BBB development and homeostasis. " 10/01/2014 - "Megalencephalic leukoencephalopathy with subcortical cysts protein 1 regulates glial surface localization of GLIALCAM from fish to humans."
2.	Membrane Proteins (Integral Membrane Proteins)IBA 12/01/2021 - "MLC1 is a membrane protein mainly expressed in astrocytes, and genetic mutations lead to the development of a leukodystrophy, megalencephalic leukoencephalopathy with subcortical cysts disease. " 12/01/2019 - "Megalencephalic leukoencephalopathy with subcortical cysts protein-1 (MLC1) is a membrane protein expressed by perivascular astrocytes. " 06/01/2014 - "Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare leukodystrophy caused by mutations in the gene encoding MLC1, a membrane protein mainly expressed in astrocytes in the central nervous system. " 03/01/2010 - "Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare congenital leukodystrophy caused by mutations in the MLC1 gene that encodes a membrane protein of unknown function. " 04/01/2001 - "Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts."
3.	Protons (Proton)IBA 12/01/2003 - "Megalencephalic leukoencephalopathy with subcortical cysts: MRI and proton spectroscopic features." 03/01/2003 - "Megalencephalic leukoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI."
4.	Interleukin-1 (Interleukin 1)IBA 10/21/2023 - "Letter to the Editor: The Application of Interleukin-1 Antagonists in Patients With Megalencephalic Leukoencephalopathy With Subcortical Cysts: Caution Warranted." 01/01/2023 - "The Effect of Interleukin-1 Antagonists on Brain Volume and Cognitive Function in Two Patients With Megalencephalic Leukoencephalopathy With Subcortical Cysts."
5.	ErbB Receptors (EGF Receptor)IBA 04/15/2016 - "Megalencephalic leukoencephalopathy with subcortical cysts protein-1 regulates epidermal growth factor receptor signaling in astrocytes."
6.	MorpholinosIBA 08/01/2012 - "Megalencephalic leukoencephalopathy with subcortical cysts type 1 (MLC1) due to a homozygous deep intronic splicing mutation (c.895-226T>G) abrogated in vitro using an antisense morpholino oligonucleotide."
7.	TOR Serine-Threonine KinasesIBA 11/01/2016 - "The most frequently mutated genes were tumor protein p53, cyclin-dependent kinase inhibitor 2A, megalencephalic leukoencephalopathy with subcortical cysts 1, rapamycin-insensitive companion of mammalian target of rapamycin, epithelial growth factor receptor, SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4, cyclin-dependent kinase inhibitor 2B, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α, Kirsten rat sarcoma viral oncogene homolog, Erb-B2 receptor tyrosine kinase 2, Serine/Threonine Kinase 11, and NK2 Homeobox 1. Sequencing results led to a change in management in 7 of 49 cases (14.3%). "
8.	Cystatin CIBA 01/01/2022 - "Although annexin A3 and cystatin C were also enhanced in the cortex at 12M, annexin A5 and the leukodystrophy-associated astrocyte proteins megalencephalic leukoencephalopathy with subcortical cysts 1 and GlialCAM were distinctly elevated in the CC. "
9.	Cyclin-Dependent Kinase Inhibitor p15IBA 11/01/2016 - "The most frequently mutated genes were tumor protein p53, cyclin-dependent kinase inhibitor 2A, megalencephalic leukoencephalopathy with subcortical cysts 1, rapamycin-insensitive companion of mammalian target of rapamycin, epithelial growth factor receptor, SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 4, cyclin-dependent kinase inhibitor 2B, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α, Kirsten rat sarcoma viral oncogene homolog, Erb-B2 receptor tyrosine kinase 2, Serine/Threonine Kinase 11, and NK2 Homeobox 1. Sequencing results led to a change in management in 7 of 49 cases (14.3%). "
10.	Cathepsin AIBA 01/01/2020 - ": 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus-Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive."

Therapies and Procedures

Therapeutics

01/01/2020 - ": 4H: Hypomyelination, hypogonadotropic hypogonadism and hypodontia; AAV: Adeno-associated virus; AD: autosomal dominant; AGS: Aicardi-Goutieres syndrome; ALSP: Axonal spheroids and pigmented glia; APGBD: Adult polyglucosan body disease; AR: autosomal recessive; ASO: Antisense oligonucleotide therapy; AxD: Alexander disease; BAEP: Brainstem auditory evoked potentials; CAA: Cerebral amyloid angiopathy; CADASIL: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CARASAL: Cathepsin A-related arteriopathy with strokes and leukoencephalopathy; CARASIL: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy; CGH: Comparative genomic hybridization; ClC2: Chloride Ion Channel 2; CMTX: Charcot-Marie-Tooth disease, X-linked; CMV: Cytomegalovirus; CNS: central nervous system; CRISP/Cas9: Clustered regularly interspaced short palindromic repeat/CRISPR-associated 9; gRNA: Guide RNA; CTX: Cerebrotendinous xanthomatosis; DNA: Deoxyribonucleic acid; DSB: Double strand breaks; DTI: Diffusion tensor imaging; FLAIR: Fluid attenuated inversion recovery; GAN: Giant axonal neuropathy; H-ABC: Hypomyelination with atrophy of basal ganglia and cerebellum; HBSL: Hypomyelination with brainstem and spinal cord involvement and leg spasticity; HCC: Hypomyelination with congenital cataracts; HEMS: Hypomyelination of early myelinated structures; HMG CoA: Hydroxy methylglutaryl CoA; HSCT: Hematopoietic stem cell transplant; iPSC: Induced pluripotent stem cells; KSS: Kearns-Sayre syndrome; L-2-HGA: L-2-hydroxy glutaric aciduria; LBSL: Leukoencephalopathy with brainstem and spinal cord involvement and elevated lactate; LCC: Leukoencephalopathy with calcifications and cysts; LTBL: Leukoencephalopathy with thalamus and brainstem involvement and high lactate; MELAS: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke; MERRF: Myoclonic epilepsy with ragged red fibers; MLC: Megalencephalic leukoencephalopathy with subcortical cysts; MLD: metachromatic leukodystrophy; MRI: magnetic resonance imaging; NCL: Neuronal ceroid lipofuscinosis; NGS: Next generation sequencing; ODDD: Oculodentodigital dysplasia; PCWH: Peripheral demyelinating neuropathy-central-dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschprung disease; PMD: Pelizaeus-Merzbacher disease; PMDL: Pelizaeus-Merzbacher-like disease; RNA: Ribonucleic acid; TW: T-weighted; VWM: Vanishing white matter; WES: whole exome sequencing; WGS: whole genome sequencing; X-ALD: X-linked adrenoleukodystrophy; XLD: X-linked dominant; XLR: X-linked recessive."