MGCPH
MCID: MCR237
MIFTS: 40

Macrocephaly/megalencephaly Syndrome, Autosomal Recessive (MGCPH)

Categories: Bone diseases, Genetic diseases, Neuronal diseases

Aliases & Classifications for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

MalaCards integrated aliases for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive:

Name: Macrocephaly/megalencephaly Syndrome, Autosomal Recessive 57 72 29 6 39 70
Mgcph 57 72
Autosomal Recessive Macrocephaly/megalencephaly Syndrome 36
Megalencephaly 44

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
two unrelated families, one north african descent and one of italian descent, have been reported (last curated august 2014)


HPO:

31
macrocephaly/megalencephaly syndrome, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

OMIM® : 57 Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014). (248000) (Updated 05-Apr-2021)

MalaCards based summary : Macrocephaly/megalencephaly Syndrome, Autosomal Recessive, also known as mgcph, is related to megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 and megalencephaly-capillary malformation-polymicrogyria syndrome. An important gene associated with Macrocephaly/megalencephaly Syndrome, Autosomal Recessive is TBC1D7 (TBC1 Domain Family Member 7), and among its related pathways/superpathways are mTOR signaling pathway and Vesicle-mediated transport. Affiliated tissues include brain, cortex and skin, and related phenotypes are myopia and psychosis

KEGG : 36 Autosomal recessive macrocephaly/megalencephaly syndrome (MGCPH) is characterized by intellectual disability, macro crania, and megalencephaly. Mutations in TBC1D7 were reported in patients. TBC1D7 forms a complex with TSC1 and TSC2 that inhibits mTORC1 signaling and limits cell growth.

UniProtKB/Swiss-Prot : 72 Macrocephaly/megalencephaly syndrome, autosomal recessive: A disorder characterized by abnormal enlargement of the cerebral hemispheres, mental retardation, large head, optic atrophy and underdeveloped skeletal musculature. Head enlargement may be evident at birth or the head may become abnormally large in the early years of life. Additional clinical features include behavioral abnormalities, psychosis, learning difficulties, prognathism, myopia and astigmatism.

Related Diseases for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Diseases related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 167)
# Related Disease Score Top Affiliating Genes
1 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 11.8
2 megalencephaly-capillary malformation-polymicrogyria syndrome 11.8
3 megalencephaly 11.7
4 polyhydramnios, megalencephaly, and symptomatic epilepsy 11.6
5 leukoencephalopathy, cystic, without megalencephaly 11.6
6 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 11.5
7 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 11.5
8 hemimegalencephaly 11.5
9 megalencephalic leukoencephalopathy with subcortical cysts 1 11.5
10 alexander disease 11.3
11 cowden syndrome 1 11.2
12 megalencephaly, autosomal dominant 11.2
13 smith-kingsmore syndrome 11.1
14 megalencephaly with dysmyelination 11.0
15 pik3ca-related overgrowth spectrum 11.0
16 focal alopecia congenital megalencephaly 10.9
17 isolated megalencephaly 10.9
18 macrocephaly, benign familial 10.9
19 macrocephaly, dysmorphic facies, and psychomotor retardation 10.9
20 mental retardation, autosomal recessive 34, with variant lissencephaly 10.9
21 neurofaciodigitorenal syndrome 10.8
22 waisman syndrome 10.8
23 mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations 10.8
24 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.5
25 polymicrogyria 10.5
26 hydrocephalus 10.5
27 polydactyly 10.4
28 overgrowth syndrome 10.4
29 alacrima, achalasia, and mental retardation syndrome 10.3
30 pik3ca-related segmental overgrowth 10.3
31 hypotonia 10.3
32 chromosome 2q35 duplication syndrome 10.2
33 epilepsy 10.1
34 leukodystrophy 10.1
35 polyhydramnios 10.1
36 autism 10.1
37 ataxia and polyneuropathy, adult-onset 10.1
38 autism spectrum disorder 10.1
39 tuberous sclerosis 10.1
40 thymoma, familial 10.0
41 cortical dysplasia, complex, with other brain malformations 10 10.0
42 thymoma 10.0
43 sotos syndrome 1 10.0
44 tuberous sclerosis 1 10.0
45 congenital heart defects, hamartomas of tongue, and polysyndactyly 10.0
46 lissencephaly 10.0
47 periventricular nodular heterotopia 10.0
48 microcephaly 10.0
49 hypoglycemia 10.0
50 gigantism 10.0

Graphical network of the top 20 diseases related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive:



Diseases related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Symptoms & Phenotypes for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Human phenotypes related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 myopia 31 occasional (7.5%) HP:0000545
2 psychosis 31 occasional (7.5%) HP:0000709
3 astigmatism 31 occasional (7.5%) HP:0000483
4 patellar subluxation 31 occasional (7.5%) HP:0010499
5 macrocephaly 31 HP:0000256
6 intellectual disability 31 HP:0001249
7 megalencephaly 31 HP:0001355
8 depressivity 31 HP:0000716
9 coarse facial features 31 HP:0000280
10 global developmental delay 31 HP:0001263
11 mandibular prognathia 31 HP:0000303
12 delayed speech and language development 31 HP:0000750
13 optic atrophy 31 HP:0000648
14 pointed chin 31 HP:0000307
15 broad forehead 31 HP:0000337
16 abnormality of the musculature 31 HP:0003011
17 adrenal medullary hypoplasia 31 HP:0008239
18 scaphocephaly 31 HP:0030799

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Head:
macrocephaly
scaphocephaly
enlarged head circumference (97th percentile)

Head And Neck Face:
pointed chin
broad forehead
prognathism

Skeletal Limbs:
patellar subluxation (1 family)

Neurologic Central Nervous System:
intellectual disability
megalencephaly
speech delay
delayed psychomotor development
enlarged corpus callosum
more
Head And Neck Eyes:
myopia (1 family)
astigmatism (1 family)

Neurologic Behavioral Psychiatric Manifestations:
depression (1 family)
psychosis (1 family)

Clinical features from OMIM®:

248000 (Updated 05-Apr-2021)

Drugs & Therapeutics for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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 Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Cochrane evidence based reviews: megalencephaly

Genetic Tests for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Genetic tests related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Macrocephaly/megalencephaly Syndrome, Autosomal Recessive 29 TBC1D7

Anatomical Context for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

MalaCards organs/tissues related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive:

40
Brain, Cortex, Skin, Cerebellum, Spinal Cord, Temporal Lobe

Publications for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Articles related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive:

(show top 50) (show all 418)
# Title Authors PMID Year
1
Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly. 61 57 6
23687350 2013
2
TBC1D7 mutations are associated with intellectual disability, macrocrania, patellar dislocation, and celiac disease. 57 6
24515783 2014
3
Macrocephaly syndromes. 61 57
17980309 2007
4
[MEGALENCEPHALY: CONSIDERATIONS WITH REFERENCE TO 7 CASES DIAGNOSED INTRA VITAM]. 57 61
14144518 1964
5
Genetic disorders associated with macrocephaly. 57
18629877 2008
6
CRADD and USP44 mutations in intellectual disability, mild lissencephaly, brain atrophy, developmental delay, strabismus, behavioural problems and skeletal anomalies. 61
33647455 2021
7
Fetal Megalencephaly with Cortical Dysplasia at 18 Gestational Weeks Related to Paternal UPD Mosaicism with PTEN Mutation. 61
33801456 2021
8
Cerebellar dysplasia related to PIK3CA mutation: a three-case series. 61
32901329 2021
9
Two further cases of polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome, caused by a truncating variant in STRADA. 61
33247513 2021
10
Homozygous missense STRADA mutation in a patient with polyhydramnios, megalencephaly and symptomatic epilepsy syndrome. 61
33605605 2021
11
STRADA-mutant human cortical organoids model megalencephaly and exhibit delayed neuronal differentiation. 61
33619909 2021
12
Insulin resistance and exaggerated insulin sensitivity triggered by single-gene mutations in the insulin signaling pathway. 61
33479580 2021
13
Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials. 61
33415748 2021
14
PIK3R2/Pik3r2 Activating Mutations Result in Brain Overgrowth and EEG Changes. 61
32856318 2020
15
Novel neonatal presentation of megalencephaly-polymicrogyria-pigmentary mosaicism syndrome (MPPM) related to MTOR mutation: Report of a case. 61
33325571 2020
16
HSF1 physically neutralizes amyloid oligomers to empower overgrowth and bestow neuroprotection. 61
33177089 2020
17
Longitudinal Evaluation of Cerebral Growth Across Childhood in Boys and Girls With Autism Spectrum Disorder. 61
33388135 2020
18
Megalencephaly-Capillary Malformation-Polymicrogyria with Cerebral Venous Thrombosis. 61
32631464 2020
19
Prenatal diagnosis of Proteus syndrome: Diagnosis of an AKT1 mutation from amniocytes. 61
32935482 2020
20
Introduction to phacomatoses (neurocutaneous disorders) in childhood. 61
32940773 2020
21
Cerebellar Astrocyte Transduction as Gene Therapy for Megalencephalic Leukoencephalopathy. 61
32372403 2020
22
Understanding Hippocampal Development in Young Children With Autism Spectrum Disorder. 61
31449875 2020
23
Detailed analysis of phenotypes and genotypes in megalencephaly-capillary malformation-polymicrogyria syndrome caused by somatic mosaicism of PIK3CA mutations. 61
32778138 2020
24
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
25
PIK3CA vascular overgrowth syndromes: an update. 61
32692051 2020
26
Septopreoptic holoprosencephaly in intracranial abnormalities: an under-diagnosed midline finding. 61
32103291 2020
27
Novel features of PIK3CA-Related Overgrowth Spectrum: Lesson from an aborted fetus presenting a de novo constitutional PIK3CA mutation. 61
31568861 2020
28
Gingival Biopsy to Detect Mosaicism in Overgrowth Syndromes: Report of Two Cases of Megalencephaly-Capillary Malformation Syndrome with Periodontal Anomalies. 61
33005459 2020
29
Megalencephalic Leukoencephalopathy: Insights Into Pathophysiology and Perspectives for Therapy. 61
33551753 2020
30
Multimodal Analysis of STRADA Function in Brain Development. 61
32457579 2020
31
One of the First Cases with PIK3CA-related Overgrowth Spectrum (PROS) in Saudi Arabia: A Case Report and Literature Review. 61
31929958 2020
32
Growth hormone deficiency in megalencephaly-capillary malformation syndrome: An association with activating mutations in PIK3CA. 61
31729162 2020
33
Variants in nuclear factor I genes influence growth and development. 61
31730271 2019
34
EML1-associated brain overgrowth syndrome with ribbon-like heterotopia. 61
31710781 2019
35
Megalencephaly syndromes associated with mutations of core components of the PI3K-AKT-MTOR pathway: PIK3CA, PIK3R2, AKT3, and MTOR. 61
31441589 2019
36
PUF60-SCRIB fusion transcript in a patient with 8q24.3 microdeletion and atypical Verheij syndrome. 61
30472487 2019
37
GATORopathies: The role of amino acid regulatory gene mutations in epilepsy and cortical malformations. 61
31625153 2019
38
De novo variants in PAK1 lead to intellectual disability with macrocephaly and seizures. 61
31504246 2019
39
Comparison of zebrafish and mice knockouts for Megalencephalic Leukoencephalopathy proteins indicates that GlialCAM/MLC1 forms a functional unit. 61
31752924 2019
40
Autosomal recessive Alport syndrome caused by a novel COL4A4 splice site mutation: a case report. 61
31686460 2019
41
Phenotypic spectrum associated with a CRADD founder variant underlying frontotemporal predominant pachygyria in the Finnish population. 61
30914828 2019
42
Differential Altered Auditory Event-Related Potential Responses in Young Boys on the Autism Spectrum With and Without Disproportionate Megalencephaly. 61
31157516 2019
43
RNASET2-deficient leukoencephalopathy mimicking congenital CMV infection and Aicardi-Goutieres syndrome: a case report with a novel pathogenic variant. 61
31349848 2019
44
[Syndromes with vascular skin anomalies]. 61
31111168 2019
45
MYCN de novo gain-of-function mutation in a patient with a novel megalencephaly syndrome. 61
30573562 2019
46
A Longitudinal Study of Local Gyrification Index in Young Boys With Autism Spectrum Disorder. 61
29850803 2019
47
Severe presentation and complex brain malformations in an individual carrying a CCND2 variant. 61
31056854 2019
48
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
49
[Malformations of cortical development and epilepsy]. 61
31603842 2019
50
Heterozygosity for Nuclear Factor One X in mice models features of Malan syndrome. 61
30503862 2019

Variations for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

ClinVar genetic disease variations for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TBC1D7 , TBC1D7-LOC100130357 NM_016495.6(TBC1D7):c.538del (p.Tyr180fs) Deletion Pathogenic 89031 rs483352922 GRCh37: 6:13307959-13307959
GRCh38: 6:13307727-13307727
2 TBC1D7 , TBC1D7-LOC100130357 NM_016495.6(TBC1D7):c.18_21del (p.Arg7fs) Deletion Pathogenic 144034 rs587777652 GRCh37: 6:13327110-13327113
GRCh38: 6:13326878-13326881
3 TBC1D7 , TBC1D7-LOC100130357 NM_016495.6(TBC1D7):c.381+143C>T SNV Uncertain significance 1033329 GRCh37: 6:13320997-13320997
GRCh38: 6:13320765-13320765

Expression for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Search GEO for disease gene expression data for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive.

Pathways for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Pathways related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive according to KEGG:

36
# Name Kegg Source Accession
1 mTOR signaling pathway hsa04150

Pathways related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.26 TBC1D7-LOC100130357 TBC1D7
2
Show member pathways
11.42 TBC1D7-LOC100130357 TBC1D7
3 10.3 TBC1D7-LOC100130357 TBC1D7

GO Terms for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Cellular components related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasmic vesicle GO:0031410 8.96 TBC1D7-LOC100130357 TBC1D7
2 ciliary basal body GO:0036064 8.62 TBC1D7-LOC100130357 TBC1D7

Biological processes related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of GTPase activity GO:0043547 9.37 TBC1D7-LOC100130357 TBC1D7
2 activation of GTPase activity GO:0090630 9.32 TBC1D7-LOC100130357 TBC1D7
3 positive regulation of protein ubiquitination GO:0031398 9.26 TBC1D7-LOC100130357 TBC1D7
4 negative regulation of TOR signaling GO:0032007 9.16 TBC1D7-LOC100130357 TBC1D7
5 response to growth factor GO:0070848 8.96 TBC1D7-LOC100130357 TBC1D7
6 negative regulation of cilium assembly GO:1902018 8.62 TBC1D7-LOC100130357 TBC1D7

Molecular functions related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 small GTPase binding GO:0031267 8.96 TBC1D7-LOC100130357 TBC1D7
2 GTPase activator activity GO:0005096 8.62 TBC1D7-LOC100130357 TBC1D7

Sources for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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