MCID: MGL013
MIFTS: 45

Megalencephaly

Categories: Fetal diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Megalencephaly

MalaCards integrated aliases for Megalencephaly:

Name: Megalencephaly 53 58 29 6 32
Macroencephaly 58

Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

ICD10 32 Q04.5
ICD10 via Orphanet 33 Q04.5
UMLS via Orphanet 72 C0221355 C2720434
Orphanet 58 ORPHA2477

Summaries for Megalencephaly

NINDS : 53 Megalencephaly, also called macrencephaly, is a condition in which an infant or child has an abnormally large, heavy, and usually malfunctioning brain. By definition, the brain weight is greater than average for the age and gender of the child. Head enlargement may be evident at birth or the head may become abnormally large in the early years of life. Megalencephaly is thought to be related to a disturbance in the regulation of cell production in the brain. In normal development, neuron proliferation - the process in which nerve cells divide to form new generations of cells - is regulated so that the correct number of cells is produced in the proper place at the appropriate time. In a megalencephalic brain, too many cells are produced either during development or progressively as part of another disorder, such as one of the neurofibromatoses or leukodystrophies. Symptoms of megalencephaly include delayed development, seizures, and corticospinal (brain cortex and spinal cord) dysfunction. Megalencephaly affects males more often than females. Unilateral megalencephaly or hemimegalencephaly is a rare condition that is characterized by the enlargement of one side of the brain. Children with this disorder may have a large, asymmetrical head accompanied by seizures, partial paralysis, and impaired cognitive development. Megalencephaly is different from macrocephaly (also called megacephaly or megalocephaly), which describes a big head, and which doesn’t necessarily indicate abnormality. Large head size is passed down through the generations in some families.

MalaCards based summary : Megalencephaly, also known as macroencephaly, is related to megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 and megalencephaly-capillary malformation-polymicrogyria syndrome. An important gene associated with Megalencephaly is PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha), and among its related pathways/superpathways are PI3K-Akt signaling pathway and Focal Adhesion. Affiliated tissues include brain, cortex and spinal cord, and related phenotypes are intellectual disability and delayed skeletal maturation

Wikipedia : 74 Megalencephaly (or macrencephaly; abbreviated MEG) is a growth development disorder in which the brain... more...

Related Diseases for Megalencephaly

Diseases in the Megalencephaly family:

Megalencephaly, Autosomal Dominant

Diseases related to Megalencephaly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 159)
# Related Disease Score Top Affiliating Genes
1 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 33.9 PIK3R2 CCND2 AKT3
2 megalencephaly-capillary malformation-polymicrogyria syndrome 33.8 PIK3R2 PIK3CA AKT3
3 megalencephaly, autosomal dominant 33.6 SCN1A PIK3CA
4 macrocephaly/megalencephaly syndrome, autosomal recessive 33.4 TBC1D7-LOC100130357 TBC1D7
5 hemimegalencephaly 32.9 SCN1A PIK3CA AKT3
6 cowden syndrome 1 32.3 PIK3R2 PIK3CA AKT3
7 hydrocephalus 30.6 PIK3R2 CCND2 AKT3
8 polydactyly 30.5 PIK3R2 CCND2 AKT3
9 polymicrogyria 29.5 SCN1A PIK3R2 PIK3CA CCND2 AKT3
10 sturge-weber syndrome 29.4 SCN1A PIK3CA
11 tuberous sclerosis 1 29.3 TBC1D7 AKT3
12 nevus, epidermal 29.3 PIK3R2 PIK3CA AKT3
13 leukoencephalopathy, cystic, without megalencephaly 12.7
14 polyhydramnios, megalencephaly, and symptomatic epilepsy 12.7
15 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 12.7
16 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 12.7
17 megalencephaly with dysmyelination 12.3
18 isolated megalencephaly 12.3
19 megalencephalic leukoencephalopathy with subcortical cysts 1 12.2
20 focal alopecia congenital megalencephaly 12.1
21 alexander disease 12.0
22 smith-kingsmore syndrome 11.7
23 macrocephaly, benign familial 11.5
24 macrocephaly, dysmorphic facies, and psychomotor retardation 11.5
25 mental retardation, autosomal recessive 34, with variant lissencephaly 11.5
26 pik3ca-related overgrowth spectrum 11.3
27 neurofaciodigitorenal syndrome 11.1
28 waisman syndrome 11.1
29 mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations 11.1
30 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.7
31 overgrowth syndrome 10.5
32 pik3ca-related segmental overgrowth 10.5
33 alacrima, achalasia, and mental retardation syndrome 10.4
34 hypotonia 10.4
35 chromosome 2q35 duplication syndrome 10.4
36 hydrocephalus, congenital, 1 10.4
37 ataxia and polyneuropathy, adult-onset 10.3
38 leukodystrophy 10.3
39 autism 10.2
40 autism spectrum disorder 10.2
41 tuberous sclerosis 10.2
42 thymoma, familial 10.2
43 epilepsy 10.2
44 thymoma 10.2
45 seizure disorder 10.2
46 sotos syndrome 1 10.1
47 congenital heart defects, hamartomas of tongue, and polysyndactyly 10.1
48 cortical dysplasia, complex, with other brain malformations 10 10.1
49 lissencephaly 10.1
50 periventricular nodular heterotopia 10.1

Graphical network of the top 20 diseases related to Megalencephaly:



Diseases related to Megalencephaly

Symptoms & Phenotypes for Megalencephaly

Human phenotypes related to Megalencephaly:

58 31 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 delayed skeletal maturation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002750
3 short neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000470
4 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000256
5 wide nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0000431
6 frontal bossing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002007
7 prominent occiput 58 31 hallmark (90%) Very frequent (99-80%) HP:0000269
8 dolichocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000268
9 abnormality of the fontanelles or cranial sutures 58 31 hallmark (90%) Very frequent (99-80%) HP:0000235
10 deeply set eye 58 31 hallmark (90%) Very frequent (99-80%) HP:0000490
11 pointed chin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000307
12 truncal obesity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001956
13 macroorchidism 58 31 frequent (33%) Frequent (79-30%) HP:0000053
14 genu valgum 58 31 frequent (33%) Frequent (79-30%) HP:0002857
15 atrial septal defect 58 31 frequent (33%) Frequent (79-30%) HP:0001631
16 long penis 58 31 frequent (33%) Frequent (79-30%) HP:0000040

GenomeRNAi Phenotypes related to Megalencephaly according to GeneCards Suite gene sharing:

26 (show all 12)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-1 10.12 PIK3CA
2 Decreased viability GR00055-A-2 10.12 PIK3CA
3 Decreased viability GR00173-A 10.12 PIK3R2
4 Decreased viability GR00221-A-1 10.12 AKT3 PIK3CA PIK3R2 STRADA
5 Decreased viability GR00221-A-2 10.12 AKT3 PIK3CA PIK3R2 STRADA
6 Decreased viability GR00221-A-3 10.12 AKT3 STRADA
7 Decreased viability GR00221-A-4 10.12 AKT3 PIK3CA PIK3R2 STRADA
8 Decreased viability GR00249-S 10.12 PIK3R2
9 Decreased viability GR00301-A 10.12 AKT3 PIK3R2
10 Decreased viability GR00402-S-2 10.12 PIK3CA
11 Decreased cell migration GR00055-A-1 9.35 AKT3 PIK3R2 STRADA
12 Decreased cell migration GR00055-A-3 9.35 PIK3CA STRADA

Drugs & Therapeutics for Megalencephaly

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations Recruiting NCT02461446

Search NIH Clinical Center for Megalencephaly

Genetic Tests for Megalencephaly

Genetic tests related to Megalencephaly:

# Genetic test Affiliating Genes
1 Megalencephaly 29

Anatomical Context for Megalencephaly

MalaCards organs/tissues related to Megalencephaly:

40
Brain, Cortex, Spinal Cord, Eye, Skin, Cerebellum, Liver

Publications for Megalencephaly

Articles related to Megalencephaly:

(show top 50) (show all 409)
# Title Authors PMID Year
1
Maternal mosaicism underlies the inheritance of a rare germline AKT3 variant which is responsible for megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome in two Roma half-siblings. 61
32446860 2020
2
Septopreoptic holoprosencephaly in intracranial abnormalities: an under-diagnosed midline finding. 61
32103291 2020
3
Cerebellar Astrocyte Transduction as Gene Therapy for Megalencephalic Leukoencephalopathy. 61
32372403 2020
4
Novel features of PIK3CA-Related Overgrowth Spectrum: Lesson from an aborted fetus presenting a de novo constitutional PIK3CA mutation. 61
31568861 2020
5
Multimodal Analysis of STRADA Function in Brain Development. 61
32457579 2020
6
Growth hormone deficiency in megalencephaly-capillary malformation syndrome: An association with activating mutations in PIK3CA. 61
31729162 2020
7
One of the First Cases with PIK3CA-related Overgrowth Spectrum (PROS) in Saudi Arabia: A Case Report and Literature Review. 61
31929958 2020
8
EML1-associated brain overgrowth syndrome with ribbon-like heterotopia. 61
31710781 2019
9
Variants in nuclear factor I genes influence growth and development. 61
31730271 2019
10
Megalencephaly syndromes associated with mutations of core components of the PI3K-AKT-MTOR pathway: PIK3CA, PIK3R2, AKT3, and MTOR. 61
31441589 2019
11
PUF60-SCRIB fusion transcript in a patient with 8q24.3 microdeletion and atypical Verheij syndrome. 61
30472487 2019
12
De novo variants in PAK1 lead to intellectual disability with macrocephaly and seizures. 61
31504246 2019
13
Comparison of zebrafish and mice knockouts for Megalencephalic Leukoencephalopathy proteins indicates that GlialCAM/MLC1 forms a functional unit. 61
31752924 2019
14
GATORopathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations. 61
31625153 2019
15
Autosomal recessive Alport syndrome caused by a novel COL4A4 splice site mutation: a case report. 61
31686460 2019
16
Phenotypic spectrum associated with a CRADD founder variant underlying frontotemporal predominant pachygyria in the Finnish population. 61
30914828 2019
17
Understanding Hippocampal Development in Young Children With Autism Spectrum Disorder. 61
31449875 2019
18
Differential Altered Auditory Event-Related Potential Responses in Young Boys on the Autism Spectrum With and Without Disproportionate Megalencephaly. 61
31157516 2019
19
[Syndromes with vascular skin anomalies]. 61
31111168 2019
20
RNASET2-deficient leukoencephalopathy mimicking congenital CMV infection and Aicardi-Goutieres syndrome: a case report with a novel pathogenic variant. 61
31349848 2019
21
Severe presentation and complex brain malformations in an individual carrying a CCND2 variant. 61
31056854 2019
22
MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome. 61
30573562 2019
23
A Longitudinal Study of Local Gyrification Index in Young Boys With Autism Spectrum Disorder. 61
29850803 2019
24
Recurrent mosaic MTOR c.5930C > T (p.Thr1977Ile) variant causing megalencephaly, asymmetric polymicrogyria, and cutaneous pigmentary mosaicism: Case report and review of the literature. 61
30569621 2019
25
Heterozygosity for Nuclear Factor One X in mice models features of Malan syndrome. 61
30503862 2019
26
[Malformations of cortical development and epilepsy]. 61
31603842 2019
27
Polymicrogyria in association with hypoglycemia points to mutation in the mTOR pathway. 61
29883676 2018
28
Novel Homozygous Deletion in STRADA Gene Associated With Polyhydramnios, Megalencephaly, and Epilepsy in 2 Siblings: Implications for Diagnosis and Treatment. 61
30311510 2018
29
From microcephaly to megalencephaly: determinants of brain size. 61
30936767 2018
30
Mutations in MAST1 Cause Mega-Corpus-Callosum Syndrome with Cerebellar Hypoplasia and Cortical Malformations. 61
30449657 2018
31
Co-occurrence of mutations in FOXP1 and PTCH1 in a girl with extreme megalencephaly, callosal dysgenesis and profound intellectual disability. 61
30181650 2018
32
Clinical pitfalls in the diagnosis of segmental overgrowth syndromes: a child with the c.2740G > A mutation in PIK3CA gene. 61
30231930 2018
33
Dysplastic megalencephaly phenotype presenting with prenatal high-output cardiac failure. 61
29594439 2018
34
Macrocephaly: Solving the Diagnostic Dilemma. 61
30086108 2018
35
PARD3 dysfunction in conjunction with dynamic HIPPO signaling drives cortical enlargement with massive heterotopia. 61
29899142 2018
36
A Novel CCND2 Mutation in a Previously Reported Case of Megalencephaly and Perisylvian Polymicrogyria with Postaxial Polydactyly and Hydrocephalus. 61
29642246 2018
37
In vitro efficacy of ARQ 092, an allosteric AKT inhibitor, on primary fibroblast cells derived from patients with PIK3CA-related overgrowth spectrum (PROS). 61
29549527 2018
38
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum: A brief report. 61
29493003 2018
39
Novel de novo ZBTB20 mutations in three cases with Primrose syndrome and constant corpus callosum anomalies. 61
29681083 2018
40
Increased cerebral blood flow on arterial spin labeling magnetic resonance imaging can localize to seizure focus in newborns: A report of 3 cases. 61
29600511 2018
41
Dendrite growth and the effect of ectopic Rheb expression on cortical neurons. 61
29447953 2018
42
mTOR mutations in Smith-Kingsmore syndrome: Four additional patients and a review. 61
28892148 2018
43
Hypoglycaemia represents a clinically significant manifestation of PIK3CA- and CCND2-associated segmental overgrowth. 61
28941273 2018
44
Dysplasia and overgrowth: magnetic resonance imaging of pediatric brain abnormalities secondary to alterations in the mechanistic target of rapamycin pathway. 61
29279945 2018
45
Novel RNASET2 Pathogenic Variants in an East Asian Child with Delayed Psychomotor Development. 61
29336640 2018
46
Repositioning of Somatic Golgi Apparatus Is Essential for the Dendritic Establishment of Adult-Born Hippocampal Neurons. 61
29217690 2018
47
Contribution of Altered Endocannabinoid System to Overactive mTORC1 Signaling in Focal Cortical Dysplasia. 61
30687088 2018
48
Commentary on "Megalencephaly-capillary malformation-polymicrogyria syndrome: the first case report in Korea". 61
29441111 2018
49
Olfactory nerve hypertrophy: a clue to the presence of ipsilateral megalencephaly. 61
29066644 2017
50
Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly. 61
28969385 2017

Variations for Megalencephaly

ClinVar genetic disease variations for Megalencephaly:

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 SCN1A NM_001165963.4(SCN1A):c.3327dup (p.Ser1110fs)duplication Pathogenic 599005 rs1559193213 2:166892659-166892660 2:166036149-166036150
2 PIK3CA NM_006218.4(PIK3CA):c.1030G>A (p.Val344Met)SNV Pathogenic/Likely pathogenic 376498 rs1057519942 3:178921548-178921548 3:179203760-179203760

Expression for Megalencephaly

Search GEO for disease gene expression data for Megalencephaly.

Pathways for Megalencephaly

Pathways related to Megalencephaly according to GeneCards Suite gene sharing:

(show top 50) (show all 87)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.86 PIK3R2 PIK3CA CCND2 AKT3
2
Show member pathways
12.78 PIK3R2 PIK3CA CCND2 AKT3
3 12.72 PIK3R2 PIK3CA CCND2 AKT3
4
Show member pathways
12.7 PIK3R2 PIK3CA AKT3
5
Show member pathways
12.69 PIK3R2 PIK3CA CCND2 AKT3
6
Show member pathways
12.64 SCN1A PIK3R2 PIK3CA AKT3
7
Show member pathways
12.52 PIK3R2 PIK3CA AKT3
8
Show member pathways
12.52 PIK3R2 PIK3CA CCND2 AKT3
9
Show member pathways
12.49 PIK3R2 PIK3CA AKT3
10
Show member pathways
12.48 PIK3R2 PIK3CA AKT3
11
Show member pathways
12.47 PIK3R2 PIK3CA AKT3
12
Show member pathways
12.47 PIK3R2 PIK3CA AKT3
13
Show member pathways
12.45 PIK3R2 PIK3CA AKT3
14 12.42 PIK3R2 PIK3CA CCND2
15
Show member pathways
12.35 PIK3R2 PIK3CA AKT3
16
Show member pathways
12.34 PIK3R2 PIK3CA AKT3
17
Show member pathways
12.32 STRADA PIK3R2 PIK3CA
18
Show member pathways
12.31 PIK3R2 PIK3CA AKT3
19
Show member pathways
12.31 PIK3R2 PIK3CA AKT3
20
Show member pathways
12.31 PIK3R2 PIK3CA AKT3
21
Show member pathways
12.3 PIK3R2 PIK3CA AKT3
22
Show member pathways
12.3 PIK3R2 PIK3CA AKT3
23 12.3 PIK3R2 PIK3CA AKT3
24
Show member pathways
12.29 PIK3R2 PIK3CA CCND2 AKT3
25
Show member pathways
12.28 STRADA PIK3R2 PIK3CA AKT3
26
Show member pathways
12.26 PIK3R2 PIK3CA AKT3
27
Show member pathways
12.26 PIK3R2 PIK3CA CCND2 AKT3
28 12.24 PIK3R2 PIK3CA AKT3
29
Show member pathways
12.23 PIK3R2 PIK3CA AKT3
30
Show member pathways
12.23 PIK3R2 PIK3CA AKT3
31
Show member pathways
12.22 PIK3R2 PIK3CA AKT3
32 12.21 PIK3R2 PIK3CA AKT3
33 12.21 PIK3R2 PIK3CA CCND2
34
Show member pathways
12.14 PIK3R2 PIK3CA CCND2 AKT3
35
Show member pathways
12.13 PIK3R2 PIK3CA AKT3
36
Show member pathways
12.12 PIK3R2 PIK3CA AKT3
37
Show member pathways
12.12 STRADA PIK3R2 AKT3
38
Show member pathways
12.11 PIK3R2 PIK3CA AKT3
39
Show member pathways
12.08 PIK3R2 PIK3CA AKT3
40
Show member pathways
12.05 PIK3R2 PIK3CA AKT3
41
Show member pathways
12.05 PIK3R2 PIK3CA AKT3
42
Show member pathways
12.05 PIK3R2 PIK3CA CCND2 AKT3
43 12.05 PIK3R2 PIK3CA CCND2 AKT3
44
Show member pathways
12.04 PIK3R2 PIK3CA AKT3
45 12.01 PIK3R2 PIK3CA AKT3
46 12 PIK3R2 PIK3CA AKT3
47 11.99 PIK3R2 PIK3CA AKT3
48
Show member pathways
11.98 PIK3R2 PIK3CA CCND2
49 11.97 PIK3R2 PIK3CA AKT3
50 11.95 PIK3R2 PIK3CA AKT3

GO Terms for Megalencephaly

Cellular components related to Megalencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 phosphatidylinositol 3-kinase complex GO:0005942 8.62 PIK3R2 PIK3CA

Biological processes related to Megalencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein phosphorylation GO:0006468 9.46 STRADA PIK3CA CCND2 AKT3
2 phosphatidylinositol phosphorylation GO:0046854 9.43 PIK3R2 PIK3CA
3 phosphatidylinositol-mediated signaling GO:0048015 9.4 PIK3R2 PIK3CA
4 phosphatidylinositol 3-kinase signaling GO:0014065 9.37 PIK3R2 PIK3CA
5 positive regulation of TOR signaling GO:0032008 9.32 PIK3CA AKT3
6 negative regulation of TOR signaling GO:0032007 9.26 TBC1D7-LOC100130357 TBC1D7
7 response to growth factor GO:0070848 8.96 TBC1D7-LOC100130357 TBC1D7
8 negative regulation of cilium assembly GO:1902018 8.62 TBC1D7-LOC100130357 TBC1D7

Molecular functions related to Megalencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein kinase activator activity GO:0030295 8.62 STRADA PIK3CA

Sources for Megalencephaly

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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