KEGG   DISEASE: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndromeHelp
Entry
H01885                      Disease                                

Name
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome;
MPPH syndrome
Description
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) is rare overgrowth disorder. MCAP [DS:H02153] and MPPH show very similar symptoms; the main symptoms are progressive megalencephaly, polymicrogyria, capillary malformations, syndactyly, and connective tissue dysplasia in the former, and progressive megalencephaly, polymicrogyria, and polydactyly in the latter. Polydactyly in MPPH seems to be a variable feature presenting with varied severity in both upper and lower limbs. MCAP and MPPH have been shown to result from gain-of-function mutations in the mTOR-pathway.
Category
Congenital malformation
Brite
Human diseases [BR:br08402]
 Congenital malformations
  Other congenital malformations
   H01885  Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome
Human diseases in ICD-11 classification [BR:br08403]
 20 Developmental anomalies
  Multiple developmental anomalies or syndromes
   LD2C  Overgrowth syndromes
    H01885  Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome
BRITE hierarchy
Pathway
hsa04150 mTOR signaling pathway   
Gene
(MPPH1) PIK3R2 [HSA:5296] [KO:K02649]
(MPPH2) AKT3 [HSA:10000] [KO:K04456]
(MPPH3) CCND2 [HSA:894] [KO:K10151]
Other DBs
ICD-11: LD2C
ICD-10: Q87.3
MeSH: C566381
OMIM: 603387 615937 615938
Reference
PMID:9129744
  Authors
Moore CA, Toriello HV, Abuelo DN, Bull MJ, Curry CJ, Hall BD, Higgins JV, Stevens CA, Twersky S, Weksberg R, Dobyns WB
  Title
Macrocephaly-cutis marmorata telangiectatica congenita: a distinct disorder with developmental delay and connective tissue abnormalities.
  Journal
Reference
  Authors
Mirzaa G, Dodge NN, Glass I, Day C, Gripp K, Nicholson L, Straub V, Voit T, Dobyns WB
  Title
Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus: a rare brain malformation syndrome associated with mental retardation and seizures.
  Journal
Neuropediatrics 35:353-9 (2004)
DOI:10.1055/s-2004-830497
Reference
  Authors
Akgumus G, Chang F, Li MM
  Title
Overgrowth Syndromes Caused by Somatic Variants in the Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Pathway.
  Journal
J Mol Diagn 19:487-497 (2017)
DOI:10.1016/j.jmoldx.2017.04.001
Reference
  Authors
Zamora TG, Roberts KD
  Title
Four-year follow-up of megalencephaly, polymicrogyria, postaxial polydactyly and hydrocephalus (MPPH) syndrome.
  Journal
BMJ Case Rep 2013:bcr2012007826 (2013)
DOI:10.1136/bcr-2012-007826
Reference
  Authors
Negishi Y, Miya F, Hattori A, Johmura Y, Nakagawa M, Ando N, Hori I, Togawa T, Aoyama K, Ohashi K, Fukumura S, Mizuno S, Umemura A, Kishimoto Y, Okamoto N, Kato M, Tsunoda T, Yamasaki M, Kanemura Y, Kosaki K, Nakanishi M, Saitoh S
  Title
A combination of genetic and biochemical analyses for the diagnosis of PI3K-AKT-mTOR pathway-associated megalencephaly.
  Journal
BMC Med Genet 18:4 (2017)
DOI:10.1186/s12881-016-0363-6
Reference
  Authors
Mirzaa GM, Conway RL, Gripp KW, Lerman-Sagie T, Siegel DH, deVries LS, Lev D, Kramer N, Hopkins E, Graham JM Jr, Dobyns WB
  Title
Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis.
  Journal
Am J Med Genet A 158A:269-91 (2012)
DOI:10.1002/ajmg.a.34402
Reference
  Authors
Riviere JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, Gripp KW, Nikkel SM, Worthylake T, Sullivan CT, Ward TR, Butler HE, Kramer NA, Albrecht B, Armour CM, Armstrong L, Caluseriu O, Cytrynbaum C, Drolet BA, Innes AM, Lauzon JL, Lin AE, Mancini GM, Meschino WS, Reggin JD, Saggar AK, Lerman-Sagie T, Uyanik G, Weksberg R, Zirn B, Beaulieu CL, Majewski J, Bulman DE, O'Driscoll M, Shendure J, Graham JM Jr, Boycott KM, Dobyns WB
  Title
De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.
  Journal
Nat Genet 44:934-40 (2012)
DOI:10.1038/ng.2331
Reference
  Authors
Mirzaa GM, Parry DA, Fry AE, Giamanco KA, Schwartzentruber J, Vanstone M, Logan CV, Roberts N, Johnson CA, Singh S, Kholmanskikh SS, Adams C, Hodge RD, Hevner RF, Bonthron DT, Braun KP, Faivre L, Riviere JB, St-Onge J, Gripp KW, Mancini GM, Pang K, Sweeney E, van Esch H, Verbeek N, Wieczorek D, Steinraths M, Majewski J, Boycott KM, Pilz DT, Ross ME, Dobyns WB, Sheridan EG
  Title
De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome.
  Journal
Nat Genet 46:510-5 (2014)
DOI:10.1038/ng.2948
LinkDB All DBs

» Japanese version

DBGET integrated database retrieval system