Details of Disease

General Information of Disease (ID: DISK9A1M)

• Disease Name: Megalencephalic leukoencephalopathy with subcortical cysts
• Synonyms: megalencephaly-cystic leukodystrophy; megalencephalic leukoencephalopathy with subcortical cysts 1; MLC1; megalencephaly-cystic leukodystrophy syndrome; Van der Knaap syndrome; megalencephalic leukoencephalopathy with subcortical cysts type 1; Vacuolating megalencephalic leukoencephalopathy with subcortical cysts; MLC; megalencephalic leukodystrophy
• Definition: Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a form of leukodystrophy that is characterized by infantile-onset macrocephaly, often with mild neurologic signs at presentation (such as mild motor delay), which worsen with time, leading to poor ambulation, falls, ataxia, spasticity, increasing seizures and cognitive decline. Brain magnetic resonance imaging reveals diffusely abnormal and mildly swollen white matter as well as subcortical cysts in the anterior temporal and frontoparietal regions.
• Disease Hierarchy:
  DISVY1TT: Leukodystrophy
  DISZGBT7: Leukoencephalopathy, megalencephalic
  DISK9A1M: Megalencephalic leukoencephalopathy with subcortical cysts
• Disease Identifiers:
  MONDO ID: MONDO_0011391
  MESH ID: C536141
  UMLS CUI: C1858854
  MedGen ID: 347006
  Orphanet ID: 2478
  SNOMED CT ID: 703536004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MYL7	OT7ZNDP4	Limited	Genetic Variation	[1]
HEPACAM	OT1MJ51D	Supportive	Autosomal dominant	[2]
MLC1	OTCNZLSP	Supportive	Autosomal dominant	[2]
LGALS14	OTOR23GX	Strong	Biomarker	[3]
LRRC8A	OT23OE7H	Strong	Biomarker	[4]
MYL2	OT78PC0C	Strong	Genetic Variation	[5]
MYL9	OT6B22JB	Strong	Genetic Variation	[5]
NUP93	OT4J2VAL	Strong	Biomarker	[6]
RAB6A	OTLS86J5	Strong	Biomarker	[7]
TMCO1	OTSME34W	Strong	Genetic Variation	[8]
DUSP4	OT6WAO12	Definitive	Altered Expression	[9]

References

• [1] Megalencephalic leukoencephalopathy with subcortical cysts: Characterization of disease variants.Neurology. 2018 Apr 17;90(16):e1395-e1403. doi: 10.1212/WNL.0000000000005334. Epub 2018 Mar 21.
• [2] Megalencephalic Leukoencephalopathy with Subcortical Cysts. 2003 Aug 11 [updated 2023 Jul 27]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [3] Leukoencephalopathy-causing CLCN2 mutations are associated with impaired Cl(-) channel function and trafficking.J Physiol. 2017 Nov 15;595(22):6993-7008. doi: 10.1113/JP275087. Epub 2017 Oct 9.
• [4] GlialCAM/MLC1 modulates LRRC8/VRAC currents in an indirect manner: Implications for megalencephalic leukoencephalopathy.Neurobiol Dis. 2018 Nov;119:88-99. doi: 10.1016/j.nbd.2018.07.031. Epub 2018 Aug 1.
• [5] Leukoencephalopathy associated with 11q24 deletion involving the gene encoding hepatic and glial cell adhesion molecule in two patients.Eur J Med Genet. 2015 Sep;58(9):492-6. doi: 10.1016/j.ejmg.2015.06.008. Epub 2015 Jul 17.
• [6] Visceral leishmaniasis: A novel nuclear envelope protein 'nucleoporins-93 (NUP-93)' from Leishmania donovani prompts macrophage signaling for T-cell activation towards host protective immune response.Cytokine. 2019 Jan;113:200-215. doi: 10.1016/j.cyto.2018.07.005. Epub 2018 Jul 9.
• [7] Recombinant Leishmania Rab6 (rLdRab6) is recognized by sera from visceral leishmaniasis patients.Exp Parasitol. 2016 Nov;170:135-147. doi: 10.1016/j.exppara.2016.09.010. Epub 2016 Sep 22.
• [8] Identification of novel mutations in MLC1 responsible for megalencephalic leukoencephalopathy with subcortical cysts.Hum Genet. 2002 Mar;110(3):279-83. doi: 10.1007/s00439-002-0682-x. Epub 2002 Feb 8.
• [9] Immunomodulation of dual specificity phosphatase 4 during visceral leishmaniasis.Microbes Infect. 2018 Feb;20(2):111-121. doi: 10.1016/j.micinf.2017.10.009. Epub 2017 Nov 10.