KEGG DISEASE: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

KEGG

DISEASE: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

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 in ICD-11 classification [BR:br08403]
20 Developmental anomalies
  Multiple developmental anomalies or syndromes
   LD2C  Overgrowth syndromes
    H01885  Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
  nt06530  PI3K signaling
   H01885  Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

Pathway

PI3K-Akt signaling pathway

Network

nt06530 PI3K signaling

Gene

(MPPH1) PIK3R2 [HSA:5296] [KO:K02649]
(MPPH2) AKT3 [HSA:10000] [KO:K04456]
(MPPH3) CCND2 [HSA:894] [KO:K10151]

Other DBs

ICD-11:

MeSH:

OMIM:

603387 615937 615938

Reference

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

Am J Med Genet 70:67-73 (1997)
DOI:10.1002/(SICI)1096-8628(19970502)70:1<67::AID-AJMG13>3.0.CO;2-V

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

» Japanese version

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