Megalencephaly disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

NINDS: ⁵² 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 CCND2 (Cyclin D2), and among its related pathways/superpathways are Signal Transduction and PIP3 activates AKT signaling. Affiliated tissues include brain, spinal cord and cortex, and related phenotypes are macrocephaly and intellectual disability

Orphanet: ⁵⁸ A rare central nervous system malformation characterized by an abnormally large brain, accompanied by abnormal head circumference measurements evident at birth or developing over the first years of life. The condition can be unilateral or bilateral and affects males more often than females. There is no typical pattern of symptoms, but mental retardation, seizures, and other neurologic abnormalities have been reported.

Wikipedia: ⁷⁵ Megalencephaly (or macrencephaly; abbreviated MEG) is a growth development disorder in which the brain... more...

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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 233)

#	Related Disease	Score	Top Affiliating Genes
1	megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1	33.0	PIK3R2 CCND2 AKT3
2	megalencephaly-capillary malformation-polymicrogyria syndrome	32.9	PIK3R2 PIK3CA AKT3
3	macrocephaly/megalencephaly syndrome, autosomal recessive	32.6	TBC1D7-LOC100130357 TBC1D7
4	hemimegalencephaly	32.1	PTEN PIK3CA MTOR AKT3
5	cowden syndrome 1	31.6	PTEN PIK3R2 PIK3CA MTOR AKT3
6	polymicrogyria	30.7	PTEN PIK3R2 PIK3CA CCND2 AKT3
7	hydrocephalus	30.6	PTEN PIK3R2 MTOR CCND2 AKT3
8	polydactyly	30.5	PTCH1 PIK3R2 CCND2 AKT3
9	tuberous sclerosis	30.2	TBC1D7 PIK3CA MTOR
10	polymicrogyria, bilateral perisylvian, x-linked	29.9	PIK3R2 PIK3CA CCND2 AKT3
11	nevus, epidermal	29.4	PTEN PIK3R2 PIK3CA MTOR AKT3
12	basal cell nevus syndrome	29.3	PTEN PTCH1 MYCN
13	cowden syndrome	29.3	PTEN PTCH1 PIK3R2 PIK3CA MTOR AKT3
14	medulloblastoma	28.8	PTEN PTCH1 PIK3CA MYCN MTOR CCND2
15	polyhydramnios, megalencephaly, and symptomatic epilepsy	11.6
16	megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2	11.6
17	leukoencephalopathy, cystic, without megalencephaly	11.5
18	megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3	11.5
19	megalencephalic leukoencephalopathy with subcortical cysts	11.5
20	megalencephaly, autosomal dominant	11.4
21	alexander disease	11.3
22	macrocephaly, dysmorphic facies, and psychomotor retardation	11.2
23	megalencephaly with dysmyelination	11.1
24	smith-kingsmore syndrome	11.1
25	intellectual developmental disorder, autosomal recessive 34, with variant lissencephaly	11.1
26	neurofaciodigitorenal syndrome	11.0
27	isolated megalencephaly	10.9
28	macrocephaly, benign familial	10.9
29	megalencephalic leukoencephalopathy with subcortical cysts 1	10.9
30	focal alopecia congenital megalencephaly	10.9
31	mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations	10.9
32	capillary malformations, congenital	10.5
33	overgrowth syndrome	10.5
34	hypotonia	10.3
35	polydactyly, postaxial, type a1	10.2
36	chromosome 2q35 duplication syndrome	10.2
37	hydrocephalus, congenital, 1	10.2
38	generalized lymphatic anomaly	10.2	PIK3CA MTOR
39	lung oat cell carcinoma	10.2	PTEN PIK3CA
40	thyroid tumor	10.2	PTEN PIK3CA
41	autism spectrum disorder	10.2
42	breast juvenile papillomatosis	10.2	PTEN PIK3CA
43	epilepsy	10.2
44	pik3ca-related overgrowth spectrum	10.2
45	autism	10.1
46	leukodystrophy	10.1
47	polyhydramnios	10.1
48	subependymal glioma	10.1	TBC1D7 PTEN MTOR
49	benign ependymoma	10.1	TBC1D7 PTEN MTOR
50	subependymal giant cell astrocytoma	10.1	TBC1D7 PTEN MTOR

Graphical network of the top 20 diseases related to Megalencephaly:

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Symptoms & Phenotypes for Megalencephaly

Human phenotypes related to Megalencephaly:

⁵⁸ ³⁰ (show all 16)

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

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

²⁵ (show all 29)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased viability	GR00055-A-1	10.66	MTOR PIK3CA
2	Decreased viability	GR00055-A-2	10.66	MTOR PIK3CA
3	Decreased viability	GR00173-A	10.66	PIK3R2
4	Decreased viability	GR00221-A-1	10.66	AKT3 MAST1 MTOR PIK3CA PIK3R2 STRADA
5	Decreased viability	GR00221-A-2	10.66	AKT3 PIK3CA PIK3R2 STRADA
6	Decreased viability	GR00221-A-3	10.66	AKT3 MAST1 STRADA
7	Decreased viability	GR00221-A-4	10.66	AKT3 MAST1 MTOR PIK3CA PIK3R2 STRADA
8	Decreased viability	GR00249-S	10.66	MAST1 PIK3R2
9	Decreased viability	GR00301-A	10.66	AKT3 PIK3R2
10	Decreased viability	GR00342-S-1	10.66	MTOR
11	Decreased viability	GR00342-S-2	10.66	MTOR
12	Decreased viability	GR00402-S-2	10.66	MAST1 PIK3CA
13	Increased shRNA abundance (Z-score > 2)	GR00366-A-105	9.5	MTOR
14	Increased shRNA abundance (Z-score > 2)	GR00366-A-151	9.5	PTEN
15	Increased shRNA abundance (Z-score > 2)	GR00366-A-16	9.5	PTEN
16	Increased shRNA abundance (Z-score > 2)	GR00366-A-168	9.5	PTEN
17	Increased shRNA abundance (Z-score > 2)	GR00366-A-172	9.5	RNASET2
18	Increased shRNA abundance (Z-score > 2)	GR00366-A-19	9.5	RNASET2
19	Increased shRNA abundance (Z-score > 2)	GR00366-A-214	9.5	PTEN
20	Increased shRNA abundance (Z-score > 2)	GR00366-A-42	9.5	PTEN
21	Increased shRNA abundance (Z-score > 2)	GR00366-A-60	9.5	MTOR PIK3CA
22	Increased shRNA abundance (Z-score > 2)	GR00366-A-63	9.5	PTEN
23	Increased shRNA abundance (Z-score > 2)	GR00366-A-66	9.5	PTEN
24	Increased shRNA abundance (Z-score > 2)	GR00366-A-85	9.5	MTOR
25	Increased shRNA abundance (Z-score > 2)	GR00366-A-87	9.5	PTEN
26	Increased shRNA abundance (Z-score > 2)	GR00366-A-93	9.5	PTEN
27	Decreased substrate adherent cell growth	GR00193-A-1	9.43	MAST1 STRADA
28	Decreased substrate adherent cell growth	GR00193-A-2	9.43	AKT3
29	Decreased substrate adherent cell growth	GR00193-A-3	9.43	AKT3 MAST1 STRADA

MGI Mouse Phenotypes related to Megalencephaly:

⁴⁵

#	Description	MGI Source Accession	Score	Top Affiliating Genes
1	nervous system	MP:0003631	10.06	AKT3 CCND2 MAST1 MLC1 MTOR MYCN
2	homeostasis/metabolism	MP:0005376	9.97	AKT3 CCND2 CRADD FOXP1 MLC1 MTOR
3	muscle	MP:0005369	9.91	FOXP1 MTOR MYCN PIK3CA PIK3R2 PTCH1
4	growth/size/body region	MP:0005378	9.77	AKT3 CCND2 FOXP1 MLC1 MTOR MYCN
5	behavior/neurological	MP:0005386	9.4	AKT3 CCND2 FOXP1 MLC1 MTOR MYCN

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Drugs & Therapeutics for Megalencephaly

Interventional clinical trials:

#	Name	Status	NCT ID	Phase	Drugs
1	A Phase II Double-blind Multi-center, Placebo-controlled Trial, to Assess the Efficacy and Safety of Alpelisib (BYL719) in Pediatric and Adult Patients With Megalencephaly-CApillary Malformation Polymicrogyria Syndrome (MCAP)	Recruiting	NCT05577754	Phase 2	Alpelisib (BYL719);Matching placebo
2	Natural History Study of Individuals With Autism and Germline Heterozygous PTEN Mutations	Recruiting	NCT02461446
3	Evaluation Nationale Des Enfants et Adultes Avec Syndromes d'Hypercroissance Dysharmonieuse National Evaluation of Patients With PIK3CA-Related Overgrowth Spectrum (PROS)	Not yet recruiting	NCT05563831

Search NIH Clinical Center for Megalencephaly

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Genetic Tests for Megalencephaly

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Anatomical Context for Megalencephaly

Organs/tissues related to Megalencephaly:

MalaCards : Brain, Spinal Cord, Cortex, Eye, Temporal Lobe, Fetal Brain, Cerebellum

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Publications for Megalencephaly

Articles related to Megalencephaly:

(show top 50) (show all 480)

#	Title	Authors	PMID	Year
1	Sleep Problems in Children With Neurocutaneous Syndromes: A Cross-Sectional Study. ⁶²	Saini L...Sharawat IK	35918819	2022
2	Brain Abnormalities in PIK3CA-Related Overgrowth Spectrum: Physician, Patient, and Caregiver Experiences. ⁶²	Dexheimer J...Mirzaa GM	35857185	2022
3	[Smith-Kingsmore syndrome caused by MTOR gene variation: 2 cases and literature review]. ⁶²	Lei HH...Yang Y	36038305	2022
4	LysM-positive neurons drive Tuberous Sclerosis Complex (TSC)-associated brain lesions. ⁶²	Zhang J...Zhang Y	36115548	2022
5	Dyke-davidoff-masson syndrome: A case report of an adolescent boy at a tertiary hospital in Adamawa, North-Eastern Nigeria. ⁶²	Usman AB...Hirayama K	36149226	2022
6	Cochlear Implantation in a Profoundly Deaf Child with Cystic Leukoencephalopathy without Megalencephaly. ⁶²	Gopalakrishnan A...Alexander A	35979751	2022
7	Hemimegalencephaly: Evolution From an Atypical Focal Early Appearance on Fetal MRI to More Conventional MR Findings. ⁶²	Kakish D...Krishnan A	36120272	2022
8	Prenatal overgrowth and polydramnios: Would you think about Noonan syndrome? ⁶²	Beltrami B...Bedeschi MF	36017115	2022
9	Qualitative research with patients and caregivers of patients with PIK3CA related overgrowth spectrum: content validity of clinical outcome assessments. ⁶²	Raymond K...D'Alessio D	35829859	2022
10	Clinical Conundrum: Polyhydramnios as a Marker for a Fetal Genetic Syndrome in the Canadian Old Order Mennonite Population. ⁶²	Hutson J...Rupar CA	35131504	2022
11	Thyroid hypogenesis is associated with a novel AKT3 germline variant that causes megalencephaly and cortical malformation. ⁶²	Mori J...Chiyonobu T	35665751	2022
12	Equivocal evidence for a link between megalencephaly-related genes and primate brain size evolution. ⁶²	DeCasien AR...Higham JP	35764790	2022
13	Phenotypic and molecular characterization of five patients with PIK3CA-related overgrowth spectrum (PROS). ⁶²	Gokpinar Ili E...Ilgin Ruhi H	35238469	2022
14	Clinical and Molecular Spectrum of Sporadic Vascular Malformations: A Single-Center Study. ⁶²	Diociaiuti A...El Hachem M	35740480	2022
15	Mapping the PIK3CA-related overgrowth spectrum (PROS) patient and caregiver journey using a patient-centered approach. ⁶²	Rodriguez-Laguna L...Johnson C	35526022	2022
16	PIK3CA-related overgrowth with an uncommon phenotype: case report. ⁶²	Rotunno R...El Hachem M	35551640	2022
17	Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome (MCAP): A Rare Dynamic Genetic Disorder. ⁶²	Sarma K...Gaikwad SB	35733479	2022
18	Fetal Brain Development: Regulating Processes and Related Malformations. ⁶²	Leibovitz Z...Haddad L	35743840	2022
19	Prenatal MR Imaging Phenotype of Fetuses with Tuberous Sclerosis: An Institutional Case Series and Literature Review. ⁶²	Goergen SK...Fahey MC	35332020	2022
20	TAU ablation in excitatory neurons and postnatal TAU knockdown reduce epilepsy, SUDEP, and autism behaviors in a Dravet syndrome model. ⁶²	Shao E...Mucke L	35476595	2022
21	The utility of cerebrospinal fluid-derived cell-free DNA in molecular diagnostics for the PIK3CA-related megalencephaly-capillary malformation (MCAP) syndrome: a case report. ⁶²	Chen WL...Mirzaa GM	35483878	2022
22	Clinical and molecular data in cases of prenatal localized overgrowth disorder: major implication of genetic variants in PI3K-AKT-mTOR signaling pathway. ⁶²	Bourgon N...Collaborators	34170046	2022
23	Profiling PI3K-AKT-MTOR variants in focal brain malformations reveals new insights for diagnostic care. ⁶²	Pirozzi F...Mirzaa GM	35355055	2022
24	Clinical and Laboratory Profile of Gangliosidosis from Southern Part of India. ⁶²	Gowda VK...Benakappa N	35186388	2022
25	Endosomal trafficking defects alter neural progenitor proliferation and cause microcephaly. ⁶²	Carpentieri JA...Baffet AD	35013230	2022
26	A rare case of hemimegalencephaly diagnosed prenatally. ⁶²	Wojtowicz A...Huras H	35894497	2022
27	Brain overgrowth associated with megalencephaly-capillary malformation syndrome causing progressive Chiari and syringomyelia. ⁶²	Deleu T...Calenbergh FV	35673641	2022
28	Treating refractory corneal hydrops in a male patient with vernal keratoconjunctivitis and mental retardation: a case report. ⁶²	Shih EJ...Chen JL	35073856	2022
29	Autism spectrum disorder in a child with megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP). ⁶²	St John LJ...Rao N	34969807	2021
30	The blended phenotype of a germline RIT1 and a mosaic PIK3CA variant. ⁶²	Berland S...Douzgou S	34887308	2021
31	Longitudinal Evaluation of Cerebral Growth Across Childhood in Boys and Girls With Autism Spectrum Disorder. ⁶²	Lee JK...Nordahl CW	33388135	2021
32	Proximal variants in CCND2 associated with microcephaly, short stature, and developmental delay: A case series and review of inverse brain growth phenotypes. ⁶²	Pirozzi F...Mirzaa GM	34087052	2021
33	The Names of Things: The 2018 Bernard Sachs Lecture. ⁶²	Dobyns WB	34330614	2021
34	Siblings with megalencephalic leukoencephalopathy with subcortical cysts van der Knaap disease. ⁶²	M P S...Prasad SG	35136617	2021
35	Delineating the Smith-Kingsmore syndrome phenotype: Investigation of 16 patients with the MTOR c.5395G > A p.(Glu1799Lys) missense variant. ⁶²	Poole RL...Tatton-Brown K	34032352	2021
36	Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features. ⁶²	Zaki MS...Maroofian R	34163010	2021
37	Megalencephaly-capillary malformation syndrome and associated hydrocephalus: treatment options and revision of the literature. ⁶²	Alamar M...Hinojosa J	34047857	2021
38	The Fetus with Ganglionic Eminence Abnormality: Head Size and Extracranial Sonographic Findings Predict Genetic Diagnoses and Postnatal Outcomes. ⁶²	Goergen SK...Righini A	33958329	2021
39	Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities. ⁶²	Carmignac V...Vabres P	33833411	2021
40	STRADA-mutant human cortical organoids model megalencephaly and exhibit delayed neuronal differentiation. ⁶²	Dang LT...Parent JM	33619909	2021
41	Homozygous missense STRADA mutation in a patient with polyhydramnios, megalencephaly and symptomatic epilepsy syndrome. ⁶²	Aerden M...Devriendt K	33605605	2021
42	Functional and structural analyses of novel Smith-Kingsmore Syndrome-Associated MTOR variants reveal potential new mechanisms and predictors of pathogenicity. ⁶²	Besterman AD...Martinez-Agosto JA	34197453	2021
43	Megalencephaly Polymicrogyria Polydactyly Hydrocephalus (MPPH): A Case Report and Review of Literature. ⁶²	Ortiz JF...Patel A	34354878	2021
44	[The etiology of 340 infants with early-onset epilepsy]. ⁶²	Song TY...Tian XJ	33902223	2021
45	Medulloblastoma in the setting of megalencephaly polymicrogyria polydactyly hydrocephalus. ⁶²	Hadzipasic M...Fehnel KP	33634562	2021
46	Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials. ⁶²	Garde A...Faivre L	33415748	2021
47	CRADD and USP44 mutations in intellectual disability, mild lissencephaly, brain atrophy, developmental delay, strabismus, behavioural problems and skeletal anomalies. ⁶²	Koprulu M...Tolun A	33647455	2021
48	Cerebellar dysplasia related to PIK3CA mutation: a three-case series. ⁶²	Di Stasi M...Parazzini C	32901329	2021
49	Fetal Megalencephaly with Cortical Dysplasia at 18 Gestational Weeks Related to Paternal UPD Mosaicism with PTEN Mutation. ⁶²	Pooh RK...Chiyo H	33801456	2021
50	Novel neonatal presentation of megalencephaly-polymicrogyria-pigmentary mosaicism syndrome (MPPM) related to MTOR mutation: Report of a case. ⁶²	Taylor DL...Morley KW	33325571	2021

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Genes for Megalencephaly

Genes related to Megalencephaly (0 elite genes):

(show all 17)

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence
1	CCND2	Cyclin D2	Protein Coding	26.07	GeneCards inferred via : Disorders Publications Summaries (show sections)
2	TBC1D7	TBC1 Domain Family Member 7	Protein Coding	25.69	GeneCards inferred via : Disorders Publications Summaries (show sections)
3	STRADA	STE20 Related Adaptor Alpha	Protein Coding	25.65	GeneCards inferred via : Disorders Publications Summaries (show sections)
4	PIK3CA	Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha	Protein Coding	17.1	GeneCards inferred via : Disorders Publications (show sections)
5	AKT3	AKT Serine/Threonine Kinase 3	Protein Coding	17.04	GeneCards inferred via : Disorders Publications (show sections)
6	PIK3R2	Phosphoinositide-3-Kinase Regulatory Subunit 2	Protein Coding	16.83	GeneCards inferred via : Disorders Publications (show sections)
7	CRADD	CASP2 And RIPK1 Domain Containing Adaptor With Death Domain	Protein Coding	15.59	GeneCards inferred via : Disorders Publications (show sections)
8	PTEN	Phosphatase And Tensin Homolog	Protein Coding	8.19	GeneCards inferred via : Disorders (show sections)
9	MTOR	Mechanistic Target Of Rapamycin Kinase	Protein Coding	8.04	GeneCards inferred via : Publications (show sections)
10	MLC1	Modulator Of VRAC Current 1	Protein Coding	7.43	GeneCards inferred via : Disorders (show sections)
11	TBC1D7-LOC100130357	TBC1D7-LOC100130357 Readthrough	Protein Coding	7.38	GeneCards inferred via : Publications (show sections)
12	FOXP1	Forkhead Box P1	Protein Coding	7.21	GeneCards inferred via : Publications (show sections)
13	MYCN	MYCN Proto-Oncogene, BHLH Transcription Factor	Protein Coding	7.21	GeneCards inferred via : Publications (show sections)
14	PIDD1	P53-Induced Death Domain Protein 1	Protein Coding	7.21	GeneCards inferred via : Publications (show sections)
15	PTCH1	Patched 1	Protein Coding	7.21	GeneCards inferred via : Publications (show sections)
16	MAST1	Microtubule Associated Serine/Threonine Kinase 1	Protein Coding	6.99	GeneCards inferred via : Disorders (show sections)
17	RNASET2	Ribonuclease T2	Protein Coding	6.99	GeneCards inferred via : Disorders (show sections)

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Variations for Megalencephaly

ClinVar genetic disease variations for Megalencephaly:

⁵

#	Gene	Name	Type	Significance	ClinVarId	dbSNP ID	Position
1	PEX6	NM_000287.4(PEX6):c.1680C>G (p.Pro560=)	SNV	Uncertain Significance	1683500		GRCh37: 6:42936036-42936036 GRCh38: 6:42968298-42968298

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Expression for Megalencephaly

Search GEO for disease gene expression data for Megalencephaly.

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Pathways for Megalencephaly

Pathways related to Megalencephaly according to GeneCards Suite gene sharing:

(show top 50) (show all 57)

#	Super pathways	Score	Top Affiliating Genes
1	Signal Transduction ⁶⁶	13.73	STRADA PTEN PTCH1 PIK3R2 PIK3CA MYCN
2	PIP3 activates AKT signaling ⁶⁶ Show member pathways Intracellular signaling by second messengers ⁶⁶ PTEN Regulation ⁶⁶ Regulation of PTEN gene transcription ⁶⁶ Regulation of PTEN localization ⁶⁶	13.01	PTEN PIK3R2 PIK3CA MTOR AKT3
3	Regulation of TP53 Activity ⁶⁶ Show member pathways Regulation of TP53 Activity through Association with Co-factors ⁶⁶ Regulation of TP53 Activity through Methylation ⁶⁶ Regulation of TP53 Activity through Phosphorylation ⁶⁶ Transcriptional Regulation by TP53 ⁶⁶	12.91	PTEN PIDD1 MTOR CRADD AKT3
4	TNFR1 Pathway ⁶⁴ Show member pathways Apoptosis ⁷⁴ Apoptosis and survival TNFR1 signaling pathway ²² Apoptosis modulation by HSP70 ⁷⁴ Apoptosis through Death Receptors ⁶⁴ Apoptotic Pathways Triggered By HIV1 ⁶⁴ Ceramide signaling pathway ⁶¹ DR3 Signaling ⁶⁴ GITR Pathway ⁶⁴ HIV-1 Nef: Negative effector of Fas and TNF-alpha ⁶¹ Stimulation of the cell death response by PAK-2p34 ⁶⁶ TNF Signaling ⁶⁴ TNF-related weak inducer of apoptosis (TWEAK) signaling pathway ⁷⁴ TRAIL Pathway ⁶⁴ TWEAK Pathway ⁶⁴	12.85	PTEN PIK3R2 PIK3CA MTOR CRADD AKT3
5	NFAT and Cardiac Hypertrophy ⁶⁴ Show member pathways IGF1R Signaling ⁶⁴ Signaling Involved in Cardiac Hypertrophy ⁶⁴	12.82	PTEN PIK3R2 PIK3CA MTOR AKT3
6	IL-9 Signaling Pathways ⁶⁵ Show member pathways Adipocytokines and Insulin Signaling ⁶⁵ Common Cytokine Receptor Gamma-Chain Family Signaling Pathways ⁶⁵ Development Thrombopoietin-regulated cell processes ²² IL-15 Signaling Pathways ⁶⁵ IL-2 Signaling Pathways ⁶⁵ IL-21 Signaling Pathways ⁶⁵ IL-4 Pathway ⁶⁴ IL-4 Signaling Pathways ⁶⁵ IL-7 Signaling Pathways ⁶⁵ IL-9 Pathway ⁶⁴ Immune response IL-9 signaling pathway ²² Interleukin-9 signaling ⁶⁶	12.81	PTEN PIK3R2 PIK3CA MTOR AKT3
7	Signaling by Receptor Tyrosine Kinases ⁶⁶	12.78	PIK3R2 PIK3CA MYCN MTOR AKT3
8	PI3K-Akt signaling pathway ⁷⁴ Show member pathways Focal adhesion: PI3K-Akt-mTOR-signaling pathway ⁷⁴	12.78	STRADA PTEN PIK3R2 PIK3CA MTOR CCND2
9	Translation Insulin regulation of translation ²² Show member pathways Butyrate-induced histone acetylation ⁷⁴ Cell adhesion PLAU signaling ²² Development CNTF receptor signaling ²² Development Growth hormone signaling via PI3K/AKT and MAPK cascades ²² Overview of perturbations to host-cell autophagy, induced by distinct proteins of SARS-CoV-2 ⁷⁴ Regulation of lipid metabolism Insulin signaling-generic cascades ²² Transcription Receptor-mediated HIF regulation ²² Translation Regulation of EIF2 activity ²² Translation Regulation of EIF4F activity ²² Translation inhibitors in chronically activated PDGFRA cells ⁷⁴	12.68	PTEN PIK3R2 PIK3CA MTOR AKT3
10	Endometrial cancer ⁷⁴ Show member pathways Chromosomal and microsatellite instability in colorectal cancer ⁷⁴ Melanoma ⁷⁴ Non-small cell lung cancer ⁷⁴ Pancreatic adenocarcinoma pathway ⁷⁴ Signal transduction PTEN pathway ²²	12.64	AKT3 MTOR PIK3CA PIK3R2 PTEN
11	Malignant pleural mesothelioma ⁷⁴	12.62	PTEN PIK3CA MTOR CCND2 AKT3
12	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling ⁶⁶ Show member pathways Constitutive Signaling by Aberrant PI3K in Cancer ⁶⁶ Negative regulation of the PI3K/AKT network ⁶⁶ PI3K/AKT Signaling in Cancer ⁶⁶	12.61	PTEN PIK3R2 PIK3CA MTOR AKT3
13	Angiopoietin-like protein 8 regulatory pathway ⁷⁴ Show member pathways Insulin signaling ⁷⁴ Liver X receptor pathway ⁷⁴	12.48	PTEN PIK3R2 PIK3CA MTOR
14	Development EGFR signaling pathway ²² Show member pathways Development ERBB-family signaling ²² EGF Pathway ⁶⁴ EGFR Signaling Pathway ⁶⁷ ErbB receptor signaling network ⁶¹	12.45	AKT3 MTOR PIK3CA PIK3R2
15	Hepatocyte growth factor receptor signaling ⁷⁴ Show member pathways Apoptosis and survival Anti-apoptotic action of membrane-bound ESR1 ²² Apoptosis and survival NGF signaling pathway ²² Apoptosis and survival Role of CDK5 in neuronal death and survival ²² Development HGF signaling pathway ²² Development Neurotrophin family signaling ²² Drug-mediated inhibition of MET activation ⁶⁶ MET activates PTPN11 ⁶⁶ MET activates STAT3 ⁶⁶ PLC-gamma1 signalling ⁶⁶ Trk receptor signaling mediated by PI3K and PLC-gamma ⁶¹ TRKA activation by NGF ⁶⁶	12.42	PTEN PIK3R2 PIK3CA AKT3
16	NF-kappaB Pathway ⁷⁰ Show member pathways Akt Pathway ⁷⁰ Apoptosis Pathway ⁷⁰	12.39	PIK3R2 PIK3CA MTOR AKT3
17	Breast cancer pathway ⁷⁴ Show member pathways Embryonic stem cell pluripotency pathways ⁷⁴	12.37	PTEN PIK3R2 PIK3CA MTOR AKT3
18	CD28 co-stimulation ⁶⁶ Show member pathways Activation of AKT2 ⁶⁶ CD28 dependent PI3K/Akt signaling ⁶⁶ CD28 dependent Vav1 pathway ⁶⁶ Costimulation by the CD28 family ⁶⁶ CTLA4 Signaling ⁶⁴ VEGFR2 mediated vascular permeability ⁶⁶	12.35	PIK3R2 PIK3CA MTOR AKT3
19	Immune response Fc epsilon RI pathway ²² Show member pathways Fc-epsilon receptor I signaling in mast cells ⁶¹ Immune response BCR pathway ²²	12.29	PTEN PIK3R2 PIK3CA AKT3
20	Signaling by VEGF ⁶⁶ Show member pathways VEGFA-VEGFR2 Pathway ⁶⁶	12.26	PIK3R2 PIK3CA MTOR AKT3
21	B Cell Receptor Signaling Pathway ⁶⁷ Show member pathways T Cell Receptor Signaling Pathway ⁶⁷	12.19	PTEN PIK3R2 PIK3CA MTOR AKT3
22	Development Endothelin-1/EDNRA transactivation of EGFR ²² Show member pathways Cytoskeleton remodeling FAK signaling ²² Development Endothelin-1/EDNRA signaling ²²	12.15	PIK3R2 PIK3CA MTOR AKT3
23	Focal adhesion ⁷⁴	12.15	PTEN PIK3R2 PIK3CA CCND2 AKT3
24	AMPK Enzyme Complex Pathway ⁶⁴ Show member pathways Chromatin Remodeling ⁶⁴	12.12	STRADA PIK3R2 MTOR AKT3
25	Transcription Androgen Receptor nuclear signaling ²² Show member pathways Translation Non-genomic (rapid) action of Androgen Receptor ²²	12.05	PTEN PIK3CA MTOR AKT3
26	MAPK Signaling: Mitogens ⁶⁵ Show member pathways Akt Signaling Pathway ⁶⁵	12.03	AKT3 CCND2 MTOR PIK3CA PIK3R2 PTEN
27	Fragile X syndrome ⁷⁴ Show member pathways Pilocytic astrocytoma ⁷⁴	11.99	TBC1D7-LOC100130357 PTEN MTOR
28	GDNF signaling ⁷⁴	11.99	PTEN MYCN MTOR AKT3
29	MAPK Pathway ⁷⁰ Show member pathways Toll-like Receptor Pathway ⁷⁰	11.97	PIK3R2 PIK3CA AKT3
30	IL2 signaling events mediated by STAT5 ⁶¹ Show member pathways IL2 signaling events mediated by PI3K ⁶¹ IL2-mediated signaling events ⁶¹ Interleukin-2 signaling ⁶⁶	11.97	PIK3CA MTOR CCND2
31	AMP-activated protein kinase signaling ⁷⁴ Show member pathways AMPK Signaling Pathway ⁶⁷ Leptin and adiponectin ⁷⁴	11.96	STRADA PIK3R2 PIK3CA MTOR AKT3
32	Development EGFR signaling via small GTPases ²² Show member pathways Development EGFR signaling via PIP3 ²² Development PDGF signaling via MAPK cascades ²²	11.9	PTEN PIK3R2 PIK3CA AKT3
33	Development IGF-1 receptor signaling ²² Show member pathways Immune response IL-4 signaling pathway ²² Signal transduction AKT signaling ²²	11.9	PTEN PIK3R2 PIK3CA MTOR CCND2 AKT3
34	Notch Signaling Pathways ⁶⁵	11.88	AKT3 MTOR PIK3R2
35	TGF-beta Signaling Pathways ⁶⁵	11.86	PIK3R2 MTOR AKT3
36	p53 transcriptional gene network ⁷⁴	11.84	PTEN PIDD1 MTOR
37	DNA damage response (only ATM dependent) ⁷⁴	11.83	PTEN PIK3R2 PIK3CA CCND2
38	TP53 Regulates Metabolic Genes ⁶⁶	11.81	PTEN MTOR AKT3
39	Small cell lung cancer ⁷⁴	11.79	PTEN PIK3R2 PIK3CA AKT3
40	Thyroid hormones production and peripheral downstream signaling effects ⁷⁴	11.78	AKT3 MTOR PIK3CA
41	VEGF Pathway (Tocris) ⁷⁰ Show member pathways Sorafenib Pharmacodynamics ⁶⁰	11.75	PIK3R2 PIK3CA AKT3
42	mTOR Pathway ⁷⁰ Show member pathways TGF-beta Pathway ⁷⁰	11.69	AKT3 MTOR PIK3CA PIK3R2
43	Pathways affected in adenoid cystic carcinoma ⁷⁴	11.62	PTEN PIK3CA MYCN
44	PI3K / Akt Signaling ³	11.62	TBC1D7 PTEN PIK3R2 PIK3CA AKT3
45	BDNF-TrkB signaling ⁷⁴ Show member pathways Synaptic signaling pathways associated with autism spectrum disorder ⁷⁴	11.6	PTEN MTOR AKT3
46	IL-2 Gene Expression in Activated and Quiescent T-Cells ⁶⁴ Show member pathways TOB in T-Cell Signaling ⁶⁴	11.58	PIK3R2 PIK3CA AKT3
47	Thyroid stimulating hormone (TSH) signaling pathway ⁷⁴	11.58	PIK3R2 PIK3CA MTOR
48	Development_Leptin signaling via PI3K-dependent pathway ²²	11.52	PIK3R2 PIK3CA AKT3
49	mBDNF and proBDNF regulation of GABA neurotransmission ⁷⁴	11.35	PTEN PIK3R2 PIK3CA
50	Signaling by ALK ⁶⁶ Show member pathways STAT3 nuclear events downstream of ALK signaling ⁶⁶	11.32	MYCN PIK3CA PIK3R2

Sources

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, class IA	GO:0005943	9.46	PIK3R2 PIK3CA
2	TSC1-TSC2 complex	GO:0033596	9.13	TBC1D7-LOC100130357 TBC1D7
3	endopeptidase complex	GO:1905369	8.92	PIDD1 CRADD

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

#	Name	GO ID	Score	Top Affiliating Genes
1	negative regulation of cell size	GO:0045792	9.26	PTEN MTOR
2	phosphatidylinositol 3-kinase signaling	GO:0014065	9.1	PTEN PIK3R2 PIK3CA

Sources

Sources for Megalencephaly

¹ BitterDB

² CDC

³ Cell Signaling Technology

⁴ ClinicalTrials

⁵ ClinVar

⁶ CNVD

⁷ Cochrane Library

⁸ Cosmic

⁹ dbSNP

¹⁰ DGIdb

¹¹ Disease Ontology

¹² diseasecard

¹³ DiseaseEnhancer

¹⁴ DISEASES

¹⁵ DrugBank

¹⁶ EFO

¹⁷ ExPASy

¹⁸ FMA

¹⁹ GARD

²⁰ GeneAnalytics

²¹ GeneCards

²² GeneGo (Thomson Reuters)

²³ GeneHancer via GeneCards

²⁴ GeneReviews

²⁵ GenomeRNAi

²⁶ GEO DataSets

²⁷ GO

²⁸ GTR

²⁹ HMDB

³⁰ HPO

³¹ ICD10

³² ICD10 via Orphanet

³³ ICD11

³⁴ ICD9CM

³⁵ IUPHAR

³⁶ LifeMap

³⁷ LncRNADisease

³⁸ LOVD

³⁹ MalaCards

⁴⁰ MedGen

⁴¹ MedlinePlus

⁴² MedlinePlus Genetics

⁴³ MeSH

⁴⁴ MESH via Orphanet

⁴⁵ MGI

⁴⁶ miR2Disease

⁴⁷ NCBI Bookshelf

⁴⁸ NCI

⁴⁹ NCIt

⁵⁰ NDF-RT

⁵¹ NIH Clinical Center

⁵² NINDS

⁵³ Novoseek

⁵⁴ Novus Biologicals

⁵⁵ ODiseA

⁵⁶ OMIM via Orphanet

⁵⁷ OMIM® (Updated 08-Dec-2022)

⁵⁸ Orphanet

⁵⁹ PathCards

⁶⁰ PharmGKB

⁶¹ PubChem

⁶² PubMed

⁶³ PubMed Health

⁶⁴ QIAGEN

⁶⁵ R&D Systems

⁶⁶ Reactome

⁶⁷ Sino Biological

⁶⁸ SNOMED-CT

⁶⁹ SNOMED-CT via HPO

⁷⁰ Tocris

⁷¹ UMLS

⁷² UMLS via Orphanet

⁷³ UniProtKB/Swiss-Prot

⁷⁴ WikiPathways

⁷⁵ Wikipedia

MCID: MGL013 MIFTS: 48	Megalencephaly Categories: Fetal diseases, Neuronal diseases, Rare diseases	Data Licensing For inquiries, contact: [email protected]
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