MCID: MGL030
MIFTS: 42

Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Fetal diseases

Aliases & Classifications for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

MalaCards integrated aliases for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:

Name: Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 53 71 28 69
Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 23 49 24 71 13
Mpph Syndrome 23 49 24 55
Mpph 53 24 71
Megalencephaly-Postaxial Polydactyly-Polymicrogyria-Hydrocephalus Syndrome 23 24
Megalencephaly-Polymicrogyria-Postaxial Polydactyly-Hydrocephalus Syndrome 49 55
Meg-Pmg-Megacc Syndrome 53 71
Mpph1 53 71
Megalencephaly and Perisylvian Polymicrogyria with Postaxial Polydactyly and Hydrocephalus 49
Megalencephaly, Mega Corpus Callosum, and Complete Lack of Motor Development 53
Megalencephaly Mega Corpus Callosum and Complete Lack of Motor Development 71
Megalencephaly, Polymicrogyria, Mega Corpus Callosum Syndrome; Mpph 53
Megalanecephaly Polymicrogyria-Polydactyly Hydrocephalus Syndrome 69
Megalencephaly, Polymicrogyria, Mega Corpus Callosum Syndrome 53
Megalencephaly, Polymicrogyria, and Hydrocephalus Syndrome 49
Megalencephaly-Polymicrogyria-Mega Corpus Callosum Syndrome 71
Meg-Pmg-Poly-Hyd 24

Characteristics:

Orphanet epidemiological data:

55
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal dominant


HPO:

31
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1:
Inheritance autosomal dominant inheritance


GeneReviews:

23
Penetrance Although penetrance for mpph syndrome is expected to be high, to date it cannot be definitively determined to be 100% due to the identification of low-level mosaic somatic pik3r2 pathogenic variants in individuals who have only one of the core features (i.e., bilateral perisylvian polymicrogyria) [mirzaa et al 2015]...

Classifications:



Summaries for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Genetics Home Reference : 24 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome is a rare disorder that primarily affects the development of the brain. Affected individuals are born with an unusually large brain and head size (megalencephaly). The head and brain continue to grow rapidly during the first 2 years of life. MPPH syndrome is also associated with a brain abnormality called bilateral perisylvian polymicrogyria (BPP). The surface of the brain normally has many ridges or folds, called gyri. In people with BPP, an area of the brain called the perisylvian region develops too many gyri, and the folds are irregular and unusually small. Other brain abnormalities, including a buildup of fluid in the brain (hydrocephalus), have also been reported in people with MPPH syndrome.

MalaCards based summary : Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1, also known as megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome, is related to megalencephaly and hydrocephalus, and has symptoms including seizures, macrocephaly and hypertelorism. An important gene associated with Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 is PIK3R2 (Phosphoinositide-3-Kinase Regulatory Subunit 2), and among its related pathways/superpathways are Akt Signaling and Endometrial cancer. Affiliated tissues include brain, testes and kidney, and related phenotypes are Decreased viability and Decreased viability

NIH Rare Diseases : 49 MPPH syndrome is a disorder characterized by the presence of multiple birth defects and developmental delay. Classic signs and symptoms include polymicrogyria, megalencephaly, seizures, polydactyly, and hydrocephalus. Other features might include characteristic facial features, low muscle tone (hypotonia), and impaired vision. Mutations in at least three different genes have been identified that cause MPPH including PIK3R2, AKT3, and CCND2. Most cases of MPPH syndrome are new (de novo) in families with no prior history. The diagnosis of MPPH syndrome is based on physical examination, imaging studies, and genetic testing. Treatment is based on the signs and symptoms present in each person. Last updated: 5/27/2016

OMIM : 53 This disorder comprises megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome (MCAP; 602501) (summary by Gripp et al., 2009). (603387)

UniProtKB/Swiss-Prot : 71 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1: A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly- capillary malformation syndrome.

GeneReviews: NBK396098

Related Diseases for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Graphical network of the top 20 diseases related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:



Diseases related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1

Symptoms & Phenotypes for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
seizures
hydrocephalus
megalencephaly
polymicrogyria
developmental delay
more
Head And Neck Face:
frontal bossing

Head And Neck Eyes:
blindness
large eyes
wide palpebral fissures
eyelid ptosis
pale optic nerves

Skeletal Hands:
postaxial polydactyly

Head And Neck Mouth:
tent-shaped mouth
prominent philtral groove
submucous cleft palate (rare)

Head And Neck Nose:
low bridge

Skeletal Limbs:
flexion contractures at both knees

Neoplasia:
increased risk of medulloblastoma (rare)

Head And Neck Head:
macrocephaly

Skeletal Spine:
kyphosis
s-scoliosis of thoracic spine

Cardiovascular Heart:
atrial septal defect
ventricular septal defect
vascular ring
mitral regurgitation, mild

Muscle Soft Tissue:
muscle atrophy

Growth Height:
small birth length

Genitourinary Kidneys:
duplicated kidneys (rare)

Neurologic Behavioral Psychiatric Manifestations:
asperger-like features


Clinical features from OMIM:

603387

Human phenotypes related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:

55 31 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 frequent (33%) Frequent (79-30%) HP:0001250
2 macrocephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0000256
3 hypertelorism 55 31 frequent (33%) Frequent (79-30%) HP:0000316
4 hydrocephalus 55 31 hallmark (90%) Very frequent (99-80%) HP:0000238
5 megalencephaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0001355
6 depressed nasal bridge 55 31 frequent (33%) Frequent (79-30%) HP:0005280
7 abnormal nasal morphology 55 31 frequent (33%) Frequent (79-30%) HP:0005105
8 telecanthus 55 31 frequent (33%) Frequent (79-30%) HP:0000506
9 mitral regurgitation 55 31 frequent (33%) Frequent (79-30%) HP:0001653
10 narrow mouth 55 31 frequent (33%) Frequent (79-30%) HP:0000160
11 ventricular septal defect 55 31 frequent (33%) Frequent (79-30%) HP:0001629
12 high forehead 55 31 frequent (33%) Frequent (79-30%) HP:0000348
13 polymicrogyria 55 31 hallmark (90%) Very frequent (99-80%) HP:0002126
14 abnormal localization of kidney 55 31 frequent (33%) Frequent (79-30%) HP:0100542
15 postaxial hand polydactyly 55 31 hallmark (90%) Very frequent (99-80%) HP:0001162
16 frontal bossing 31 HP:0002007
17 ptosis 31 HP:0000508
18 kyphosis 31 HP:0002808
19 global developmental delay 31 HP:0001263
20 blindness 31 HP:0000618
21 skeletal muscle atrophy 31 HP:0003202
22 atrial septal defect 31 HP:0001631
23 intellectual disability, profound 31 HP:0002187
24 abnormality of the cardiac septa 55 Frequent (79-30%)
25 long palpebral fissure 31 HP:0000637
26 pachygyria 31 HP:0001302
27 hypoplasia of the corpus callosum 31 HP:0002079
28 knee flexion contracture 31 HP:0006380
29 muscular hypotonia of the trunk 31 HP:0008936
30 thoracic scoliosis 31 HP:0002943
31 postaxial polydactyly 31 HP:0100259
32 thick corpus callosum 31 HP:0007074
33 vascular ring 31 HP:0010775
34 abnormally large globe 31 HP:0001090

UMLS symptoms related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:


seizures

GenomeRNAi Phenotypes related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 according to GeneCards Suite gene sharing:

25
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00173-A 9.32 PIK3R2
2 Decreased viability GR00221-A-1 9.32 AKT3 PIK3R2
3 Decreased viability GR00221-A-2 9.32 AKT3 PIK3R2
4 Decreased viability GR00221-A-3 9.32 AKT3
5 Decreased viability GR00221-A-4 9.32 AKT3 PIK3R2
6 Decreased viability GR00301-A 9.32 AKT3 PIK3R2

Drugs & Therapeutics for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Search Clinical Trials , NIH Clinical Center for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1

Genetic Tests for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Genetic tests related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:

# Genetic test Affiliating Genes
1 Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 28 PIK3R2

Anatomical Context for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

MalaCards organs/tissues related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:

38
Brain, Testes, Kidney, Eye, Skeletal Muscle

Publications for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Articles related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:

# Title Authors Year
1
De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. ( 24705253 )
2014
2
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome: a case report. ( 22859694 )
2013
3
Significant overlap and possible identity of macrocephaly capillary malformation and megalencephaly polymicrogyria-polydactyly hydrocephalus syndromes. ( 19353582 )
2009

Variations for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

UniProtKB/Swiss-Prot genetic disease variations for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:

71
# Symbol AA change Variation ID SNP ID
1 PIK3R2 p.Gly373Arg VAR_069262 rs587776934
2 PIK3R2 p.Leu401Pro VAR_075683 rs587777624
3 PIK3R2 p.Asp557His VAR_075684 rs372272045

ClinVar genetic disease variations for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PIK3R2 NM_005027.3(PIK3R2): c.1117G> A (p.Gly373Arg) single nucleotide variant Pathogenic/Likely pathogenic rs587776934 GRCh38 Chromosome 19, 18162974: 18162974
2 PIK3R2 NM_005027.3(PIK3R2): c.1202T> C (p.Leu401Pro) single nucleotide variant Pathogenic rs587777624 GRCh38 Chromosome 19, 18163059: 18163059

Expression for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Search GEO for disease gene expression data for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1.

Pathways for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Pathways related to Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 according to GeneCards Suite gene sharing:

(show top 50) (show all 70)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.05 AKT3 CCND2 PIK3R2
2
Show member pathways
12.65 AKT3 CCND2 PIK3R2
3
Show member pathways
12.56 AKT3 CCND2 PIK3R2
4
Show member pathways
12.48 AKT3 CCND2 PIK3R2
5 12.41 AKT3 CCND2 PIK3R2
6
Show member pathways
12.35 AKT3 CCND2 PIK3R2
7
Show member pathways
12.22 AKT3 PIK3R2
8
Show member pathways
12.13 AKT3 PIK3R2
9
Show member pathways
12.13 AKT3 PIK3R2
10
Show member pathways
12.11 AKT3 PIK3R2
11
Show member pathways
12.09 AKT3 PIK3R2
12
Show member pathways
12.06 AKT3 PIK3R2
13
Show member pathways
12.06 AKT3 PIK3R2
14
Show member pathways
12.04 AKT3 PIK3R2
15 12.04 AKT3 PIK3R2
16 12.04 AKT3 PIK3R2
17
Show member pathways
12.03 AKT3 PIK3R2
18 12.03 CCND2 PIK3R2
19
Show member pathways
12.03 AKT3 CCND2 PIK3R2
20
Show member pathways
11.96 AKT3 PIK3R2
21
Show member pathways
11.95 AKT3 PIK3R2
22 11.95 AKT3 CCND2 PIK3R2
23
Show member pathways
11.94 AKT3 PIK3R2
24 11.93 CCND2 PIK3R2
25
Show member pathways
11.92 AKT3 PIK3R2
26
Show member pathways
11.89 AKT3 PIK3R2
27
Show member pathways
11.89 AKT3 PIK3R2
28
Show member pathways
11.89 AKT3 PIK3R2
29
Show member pathways
11.88 AKT3 PIK3R2
30
Show member pathways
11.88 AKT3 PIK3R2
31
Show member pathways
11.88 AKT3 CCND2 PIK3R2
32
Show member pathways
11.87 AKT3 PIK3R2
33 11.84 AKT3 PIK3R2
34 11.84 AKT3 PIK3R2
35
Show member pathways
11.82 CCND2 PIK3R2
36 11.81 AKT3 CCND2
37
Show member pathways
11.81 AKT3 CCND2 PIK3R2
38 11.8 AKT3 PIK3R2
39 11.79 AKT3 PIK3R2
40 11.79 AKT3 PIK3R2
41
Show member pathways
11.79 AKT3 CCND2 PIK3R2
42
Show member pathways
11.77 AKT3 PIK3R2
43 11.76 AKT3 PIK3R2
44 11.76 AKT3 PIK3R2
45 11.73 AKT3 PIK3R2
46 11.72 AKT3 PIK3R2
47
Show member pathways
11.7 AKT3 PIK3R2
48 11.7 AKT3 PIK3R2
49
Show member pathways
11.68 AKT3 PIK3R2
50 11.68 AKT3 PIK3R2

GO Terms for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

Sources for Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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