KEGG   DISEASE: Vici syndrome
Entry
H02133                      Disease                                
Name
Vici syndrome;
Immunodeficiency with cleft lip/palate, cataract, hypopigmentation, and absent corpus callosum
Description
Vici syndrome is a rare relentlessly progressive congenital multisystem disorder characterised by five principal features of callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency, and oculocutaneous hypopigmentation. Profound developmental delay, progressive failure to thrive, and acquired microcephaly are almost universal, suggesting an evolving (neuro) degenerative component. In most patients there is additional variable multisystem involvement that may affect virtually any organ system, including lungs, thyroid, liver, and kidneys. A skeletal myopathy is consistently associated. Recent studies identified mutations in the gene EPG5 as the cause of Vici syndrome. EPG5 is involved in autophagy, an evolutionarily conserved lysosomal degradation process that is essential for cell homeostasis.
Category
Immune system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
 04 Diseases of the immune system
  Primary immunodeficiencies
   4A01  Primary immunodeficiencies due to disorders of adaptive immunity
    H02133  Vici syndrome
Pathway-based classification of diseases [BR:br08402]
 Cellular processes
  nt06550  Lysosome biogenesis
   H02133  Vici syndrome
Network
nt06550 Lysosome biogenesis
Gene
EPG5 [HSA:57724] [KO:K23883]
Other DBs
ICD-11: 4A01.1Y
MeSH: C535566
OMIM: 242840
Reference
PMID:3344762
  Authors
Dionisi Vici C, Sabetta G, Gambarara M, Vigevano F, Bertini E, Boldrini R, Parisi SG, Quinti I, Aiuti F, Fiorilli M
  Title
Agenesis of the corpus callosum, combined immunodeficiency, bilateral cataract, and hypopigmentation in two brothers.
  Journal
Am J Med Genet 29:1-8 (1988)
DOI:10.1002/ajmg.1320290102
Reference
  Authors
Balasubramaniam S, Riley LG, Vasudevan A, Cowley MJ, Gayevskiy V, Sue CM, Edwards C, Edkins E, Junckerstorff R, Kiraly-Borri C, Rowe P, Christodoulou J
  Title
EPG5-Related Vici Syndrome: A Primary Defect of Autophagic Regulation with an Emerging Phenotype Overlapping with Mitochondrial Disorders.
  Journal
JIMD Rep 42:19-29 (2018)
DOI:10.1007/8904_2017_71
Reference
  Authors
Byrne S, Dionisi-Vici C, Smith L, Gautel M, Jungbluth H
  Title
Vici syndrome: a review.
  Journal
Orphanet J Rare Dis 11:21 (2016)
DOI:10.1186/s13023-016-0399-x
Reference
  Authors
Ehmke N, Parvaneh N, Krawitz P, Ashrafi MR, Karimi P, Mehdizadeh M, Kruger U, Hecht J, Mundlos S, Robinson PN
  Title
First description of a patient with Vici syndrome due to a mutation affecting the penultimate exon of EPG5 and review of the literature.
  Journal
Am J Med Genet A 164A:3170-5 (2014)
DOI:10.1002/ajmg.a.36772
Reference
  Authors
Cullup T, Kho AL, Dionisi-Vici C, Brandmeier B, Smith F, Urry Z, Simpson MA, Yau S, Bertini E, McClelland V, Al-Owain M, Koelker S, Koerner C, Hoffmann GF, Wijburg FA, ten Hoedt AE, Rogers RC, Manchester D, Miyata R, Hayashi M, Said E, Soler D, Kroisel PM, Windpassinger C, Filloux FM, Al-Kaabi S, Hertecant J, Del Campo M, Buk S, Bodi I, Goebel HH, Sewry CA, Abbs S, Mohammed S, Josifova D, Gautel M, Jungbluth H
  Title
Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy.
  Journal
Nat Genet 45:83-7 (2013)
DOI:10.1038/ng.2497
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KEGG   DISEASE: Neurodevelopmental disorder with parkinsonism or other movement abnormalities
Entry
H03045                      Disease                                
Name
Neurodevelopmental disorder with parkinsonism or other movement abnormalities
Description
Neurodevelopmental disorder with parkinsonism or other movement abnormalities (NEDPAM) is a novel autosomal recessive disorder caused by mutations in EPG5. The age-dependent phenotypic spectrum of this disease includes rapidly progressive adolescent-onset movement disorders, such as parkinsonism with dystonia and subsequent cognitive decline. EPG5 encodes the ectopic P-granules 5 autophagy protein, which plays a key role in autophagosome-lysosome fusion.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
 20 Developmental anomalies
  LD90  Conditions with disorders of intellectual development as a relevant clinical feature
   H03045  Neurodevelopmental disorder with parkinsonism or other movement abnormalities
Pathway-based classification of diseases [BR:br08402]
 Cellular processes
  nt06550  Lysosome biogenesis
   H03045  Neurodevelopmental disorder with parkinsonism or other movement abnormalities
Network
nt06550 Lysosome biogenesis
Gene
EPG5 [HSA:57724] [KO:K23883]
Other DBs
ICD-11: LD90.Y
OMIM: 621506
Reference
  Authors
Dafsari HS, Deneubourg C, Singh K, Maroofian R, Suprenant Z, Kho AL, Ingham NJ, Steel KP, Sheshadri P, Baur F, Hentrich L, Gerisch B, Zamani M, Alves C, Siddiqui A, Dafsari HS, Salari M, Lang AE, Harris M, Abdelaleem A, Sadeghian S, Azizimalamiri R, Galehdari H, Shariati G, Sedaghat A, Zeighami J, Calame D, Marafi D, Duan R, Boehnke A, Clark GD, Rosenfeld JA, Mohila CA, Steel D, Chopra S, Sharma S, Kohlschmidt N, Patzer S, Saffari A, Ebrahimi-Fakhari D, Cavdartepe BE, Chang IJ, Beckman E, Peters R, Fennell AP, Lo B, Averdunk L, Distelmaier F, Baethmann M, Elmslie F, Joost K, Nampoothiri S, Yesodharan D, Mandel H, Kimball A, Kline AD, Mignot C, Keren B, Laugel V, Ounap K, Devadathan K, van Berkestijn FMC, Silwal A, Koene S, Verma S, Karim MY, Boubidi C, Aziz M, ElGhazali G, Mattas L, Miryounesi M, Hashemi-Gorji F, Alavi S, Nouri N, Noruzinia M, Kavousi S, Kamath A, Jayawant S, Saneto R, Haridy NA, Kart PO, Cansu A, Joubert M, Beneteau C, Stuurman KE, Wilke M, Barakat TS, Tajsharghi H, Scardamaglia A, Vallian S, Hiz S, Shoeibi A, Boostani R, Hashemi N, Babaei M, Alsaleh NS, Porter J, Attie-Bitach T, Marzin P, Wicher D, Gold JI, Schuler E, Kashgari A, Alanazi RF, Eyaid W, Engelen M, Langeveld M, Stuve B, Li Y, Yigit G, Wollnik B, Monje MHG, Krainc D, Mencacci NE, Bakhtiari S, Kruer M, Argilli E, Sherr E, Jamshidi Y, Karimiani EG, Cheung YWS, Karin I, Zifarelli G, Bauer P, Chung WK, Lupski JR, Kurian MA, Dotsch J, von Kleist-Retzow JC, Klopstock T, Wagner M, Yip C, Roos A, Carsetti R, Dionisi-Vici C, Gautel M, Duchen MR, Antebi A, Houlden H, Fanto M, Jungbluth H
  Title
Mutations in the Key Autophagy Tethering Factor EPG5 Link Neurodevelopmental and Neurodegenerative Disorders Including Early-Onset Parkinsonism.
  Journal
Ann Neurol 98:932-950 (2025)
DOI:10.1002/ana.78013
Reference
  Authors
Sun QY, Tang FL, Zhou Y, Pan HX, Zhou X, Zhao YW, He RC, Zeng S, Wang JP, Lin W, Zeng WQ, Wang DD, Wang XJ, Liu ZH, Xu Q, Li JC, Yan XX, Guo JF, Qiu J, Tang BS
  Title
Biallelic Variants in EPG5 Gene Are Associated with Parkinson's Disease.
  Journal
Ann Neurol 98:369-385 (2025)
DOI:10.1002/ana.27242
LinkDB

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