MGCPH
MCID: MCR237
MIFTS: 32

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 75 40 73
Mgcph 57 75
Megalencephaly 44

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

32
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)

MalaCards based summary : Macrocephaly/megalencephaly Syndrome, Autosomal Recessive, also known as mgcph, is related to megalencephaly and megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1. 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 (KEGG) and PI3K / Akt Signaling. Affiliated tissues include bone and brain, and related phenotypes are macrocephaly and depressivity

UniProtKB/Swiss-Prot : 75 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 71)
# Related Disease Score Top Affiliating Genes
1 megalencephaly 34.0 AKT3 TBC1D7
2 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 12.7
3 megalencephaly-capillary malformation-polymicrogyria syndrome 12.7
4 polyhydramnios, megalencephaly, and symptomatic epilepsy 12.5
5 leukoencephalopathy, cystic, without megalencephaly 12.5
6 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 12.4
7 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 12.4
8 hemimegalencephaly 12.2
9 megalencephaly, autosomal dominant 12.2
10 megalencephaly with dysmyelination 12.1
11 isolated megalencephaly 12.1
12 focal alopecia congenital megalencephaly 12.0
13 rnase t2-deficient leukoencephalopathy 12.0
14 megalencephalic leukoencephalopathy with subcortical cysts 1 11.9
15 cowden syndrome 1 11.6
16 alexander disease 11.6
17 macrocephaly, benign familial 11.3
18 pik3ca-related overgrowth spectrum 11.1
19 neurofaciodigitorenal syndrome 11.0
20 mental retardation, autosomal recessive 34, with variant lissencephaly 11.0
21 early-onset parkinsonism-intellectual disability syndrome 11.0
22 macrocephaly, dysmorphic facies, and psychomotor retardation 11.0
23 polymicrogyria 10.5
24 hydrocephalus 10.5
25 polydactyly 10.4
26 epilepsy 10.2
27 autism 10.2
28 alacrima, achalasia, and mental retardation syndrome 10.1
29 tuberous sclerosis 10.1
30 polyhydramnios 10.1
31 achondroplasia 10.0
32 thanatophoric dysplasia, type i 10.0
33 periventricular nodular heterotopia 10.0
34 autism spectrum disorder 10.0
35 leukodystrophy 10.0
36 neonatal period electroclinical syndrome 10.0 AKT3 STXBP1
37 lennox-gastaut syndrome 9.9 AKT3 STXBP1
38 learning disability 9.9 FIBP RPS6KA3
39 cleft palate, isolated 9.9
40 macrodactyly 9.9
41 nevus, epidermal 9.9
42 sturge-weber syndrome 9.9
43 tuberous sclerosis 1 9.9
44 ataxia-telangiectasia 9.9
45 donohue syndrome 9.9
46 canavan disease 9.9
47 sudden infant death syndrome 9.9
48 band heterotopia 9.9
49 polymicrogyria, bilateral temporooccipital 9.9
50 muscle hypertrophy 9.9

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

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Head:
macrocephaly
scaphocephaly
enlarged head circumference (97th percentile)

Head And Neck Face:
broad forehead
pointed chin
prognathism

Skeletal Limbs:
patellar subluxation (1 family)

Neurologic Central Nervous System:
intellectual disability
megalencephaly
delayed psychomotor development
speech delay
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

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

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 32 HP:0000256
2 depressivity 32 HP:0000716
3 intellectual disability 32 HP:0001249
4 megalencephaly 32 HP:0001355
5 coarse facial features 32 HP:0000280
6 mandibular prognathia 32 HP:0000303
7 global developmental delay 32 HP:0001263
8 delayed speech and language development 32 HP:0000750
9 optic atrophy 32 HP:0000648
10 myopia 32 occasional (7.5%) HP:0000545
11 broad forehead 32 HP:0000337
12 psychosis 32 occasional (7.5%) HP:0000709
13 abnormality of the musculature 32 HP:0003011
14 pointed chin 32 HP:0000307
15 astigmatism 32 occasional (7.5%) HP:0000483
16 adrenal medullary hypoplasia 32 HP:0008239
17 scaphocephaly 32 HP:0030799
18 patellar subluxation 32 occasional (7.5%) HP:0010499

Drugs & Therapeutics for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Cochrane evidence based reviews: megalencephaly

Genetic Tests for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Anatomical Context for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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

41
Bone, Brain

Publications for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Variations for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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

6 (show top 50) (show all 87)
# Gene Variation Type Significance SNP ID Assembly Location
1 MLC1 NM_015166.3(MLC1): c.178-10T> A single nucleotide variant Likely pathogenic rs80358243 GRCh37 Chromosome 22, 50521612: 50521612
2 MLC1 NM_015166.3(MLC1): c.178-10T> A single nucleotide variant Likely pathogenic rs80358243 GRCh38 Chromosome 22, 50083183: 50083183
3 ABCC8 NM_000352.4(ABCC8): c.3517G> A (p.Val1173Met) single nucleotide variant Likely pathogenic rs141322087 GRCh37 Chromosome 11, 17426099: 17426099
4 ABCC8 NM_000352.4(ABCC8): c.3517G> A (p.Val1173Met) single nucleotide variant Likely pathogenic rs141322087 GRCh38 Chromosome 11, 17404552: 17404552
5 AKT3 NM_005465.4(AKT3): c.1393C> T (p.Arg465Trp) single nucleotide variant Pathogenic/Likely pathogenic rs587776935 GRCh37 Chromosome 1, 243668598: 243668598
6 AKT3 NM_005465.4(AKT3): c.1393C> T (p.Arg465Trp) single nucleotide variant Pathogenic/Likely pathogenic rs587776935 GRCh38 Chromosome 1, 243505296: 243505296
7 TBC1D7 NM_016495.5(TBC1D7): c.538delT (p.Tyr180Thrfs) deletion Pathogenic rs483352922 GRCh37 Chromosome 6, 13307959: 13307959
8 TBC1D7 NM_016495.5(TBC1D7): c.538delT (p.Tyr180Thrfs) deletion Pathogenic rs483352922 GRCh38 Chromosome 6, 13307727: 13307727
9 TBC1D7 NM_016495.5(TBC1D7): c.18_21delGAGA (p.Arg7Thrfs) deletion Pathogenic rs587777652 GRCh37 Chromosome 6, 13327110: 13327113
10 TBC1D7 NM_016495.5(TBC1D7): c.18_21delGAGA (p.Arg7Thrfs) deletion Pathogenic rs587777652 GRCh38 Chromosome 6, 13326878: 13326881
11 NSD1 NM_022455.4(NSD1): c.6050G> A (p.Arg2017Gln) single nucleotide variant Pathogenic/Likely pathogenic rs587784177 GRCh37 Chromosome 5, 176710828: 176710828
12 NSD1 NM_022455.4(NSD1): c.6050G> A (p.Arg2017Gln) single nucleotide variant Pathogenic/Likely pathogenic rs587784177 GRCh38 Chromosome 5, 177283827: 177283827
13 FAM177A1 NM_001079519.1(FAM177A1): c.297dup (p.Trp100Metfs) duplication Likely pathogenic rs730882244 GRCh38 Chromosome 14, 35077176: 35077176
14 FAM177A1 NM_001079519.1(FAM177A1): c.297dup (p.Trp100Metfs) duplication Likely pathogenic rs730882244 GRCh37 Chromosome 14, 35546382: 35546382
15 FIBP NM_198897.1(FIBP): c.673C> T (p.Gln225Ter) single nucleotide variant Pathogenic/Likely pathogenic rs786204849 GRCh38 Chromosome 11, 65885181: 65885181
16 FIBP NM_198897.1(FIBP): c.673C> T (p.Gln225Ter) single nucleotide variant Pathogenic/Likely pathogenic rs786204849 GRCh37 Chromosome 11, 65652652: 65652652
17 TPTE NM_199261.3(TPTE): c.1357-3_1357-2delTA deletion Uncertain significance rs149363218 GRCh37 Chromosome 21, 10910401: 10910402
18 TPTE NM_199261.3(TPTE): c.1357-3_1357-2delTA deletion Uncertain significance rs149363218 GRCh38 Chromosome 21, 10602055: 10602056
19 SLC25A22 NM_024698.5(SLC25A22): c.679G> A (p.Val227Met) single nucleotide variant Uncertain significance rs200603610 GRCh38 Chromosome 11, 792367: 792367
20 SLC25A22 NM_024698.5(SLC25A22): c.679G> A (p.Val227Met) single nucleotide variant Uncertain significance rs200603610 GRCh37 Chromosome 11, 792367: 792367
21 COL11A2 NM_080680.2(COL11A2): c.4559G> A (p.Arg1520His) single nucleotide variant Uncertain significance rs772567850 GRCh37 Chromosome 6, 33133517: 33133517
22 COL11A2 NM_080680.2(COL11A2): c.4559G> A (p.Arg1520His) single nucleotide variant Uncertain significance rs772567850 GRCh38 Chromosome 6, 33165740: 33165740
23 KAT6B NM_012330.3(KAT6B): c.1927A> T (p.Met643Leu) single nucleotide variant Uncertain significance rs778899637 GRCh37 Chromosome 10, 76736022: 76736022
24 KAT6B NM_012330.3(KAT6B): c.1927A> T (p.Met643Leu) single nucleotide variant Uncertain significance rs778899637 GRCh38 Chromosome 10, 74976264: 74976264
25 MT-ND4 NC_012920.1: m.12013A> G single nucleotide variant Uncertain significance rs1057516067 GRCh37 Chromosome MT, 12013: 12013
26 MT-ND4 NC_012920.1: m.12013A> G single nucleotide variant Uncertain significance rs1057516067 GRCh38 Chromosome MT, 12013: 12013
27 MT-ND4 NC_012920.1: m.12018C> G single nucleotide variant Uncertain significance rs1057516068 GRCh37 Chromosome MT, 12018: 12018
28 MT-ND4 NC_012920.1: m.12018C> G single nucleotide variant Uncertain significance rs1057516068 GRCh38 Chromosome MT, 12018: 12018
29 MT-CYB NC_012920.1: m.15246G> A single nucleotide variant Likely pathogenic rs1057516075 GRCh37 Chromosome MT, 15246: 15246
30 MT-CYB NC_012920.1: m.15246G> A single nucleotide variant Likely pathogenic rs1057516075 GRCh38 Chromosome MT, 15246: 15246
31 BTD NM_001281723.2(BTD): c.106_107delGG (p.Gly36Leufs) deletion Uncertain significance rs765906887 GRCh38 Chromosome 3, 15635479: 15635480
32 BTD NM_001281723.2(BTD): c.106_107delGG (p.Gly36Leufs) deletion Uncertain significance rs765906887 GRCh37 Chromosome 3, 15676986: 15676987
33 NFIA NM_001145511.1(NFIA): c.881delG (p.Gly294Glufs) deletion Likely pathogenic rs1057518992 GRCh37 Chromosome 1, 61824905: 61824905
34 NFIA NM_001145511.1(NFIA): c.881delG (p.Gly294Glufs) deletion Likely pathogenic rs1057518992 GRCh38 Chromosome 1, 61359233: 61359233
35 DOCK6 NM_020812.3(DOCK6): c.934C> T (p.His312Tyr) single nucleotide variant Uncertain significance rs370838036 GRCh37 Chromosome 19, 11356328: 11356328
36 DOCK6 NM_020812.3(DOCK6): c.934C> T (p.His312Tyr) single nucleotide variant Uncertain significance rs370838036 GRCh38 Chromosome 19, 11245652: 11245652
37 GLI3 NM_000168.5(GLI3): c.2000G> T (p.Arg667Leu) single nucleotide variant Uncertain significance rs373926115 GRCh37 Chromosome 7, 42012039: 42012039
38 GLI3 NM_000168.5(GLI3): c.2000G> T (p.Arg667Leu) single nucleotide variant Uncertain significance rs373926115 GRCh38 Chromosome 7, 41972440: 41972440
39 NFIB NM_001190737.1(NFIB): c.265C> T (p.Arg89Ter) single nucleotide variant Conflicting interpretations of pathogenicity rs764333096 GRCh38 Chromosome 9, 14307286: 14307286
40 NFIB NM_001190737.1(NFIB): c.265C> T (p.Arg89Ter) single nucleotide variant Conflicting interpretations of pathogenicity rs764333096 GRCh37 Chromosome 9, 14307285: 14307285
41 BICD2 NM_001003800.1(BICD2): c.1636_1638delAAT (p.Asn546del) deletion Likely pathogenic rs1064795760 GRCh38 Chromosome 9, 92719007: 92719009
42 BICD2 NM_001003800.1(BICD2): c.1636_1638delAAT (p.Asn546del) deletion Likely pathogenic rs1064795760 GRCh37 Chromosome 9, 95481289: 95481291
43 TBC1D7 NM_016495.5(TBC1D7): c.747_748insA (p.Val250Serfs) insertion Pathogenic GRCh37 Chromosome 6, 13306678: 13306678
44 TBC1D7 NM_016495.5(TBC1D7): c.747_748insA (p.Val250Serfs) insertion Pathogenic GRCh38 Chromosome 6, 13306445: 13306446
45 ANKRD11 NM_001256182.1(ANKRD11): c.6919C> T (p.Pro2307Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs575642464 GRCh38 Chromosome 16, 89279623: 89279623
46 ANKRD11 NM_001256182.1(ANKRD11): c.6919C> T (p.Pro2307Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs575642464 GRCh37 Chromosome 16, 89346031: 89346031
47 SATB2 NM_001172509.1(SATB2): c.1654_1655delAG (p.Arg552Glyfs) deletion Pathogenic GRCh37 Chromosome 2, 200173568: 200173569
48 SATB2 NM_001172509.1(SATB2): c.1654_1655delAG (p.Arg552Glyfs) deletion Pathogenic GRCh38 Chromosome 2, 199308845: 199308846
49 STXBP1 NM_003165.3(STXBP1): c.360delA (p.Lys120Asnfs) deletion Pathogenic GRCh38 Chromosome 9, 127661136: 127661136
50 STXBP1 NM_003165.3(STXBP1): c.360delA (p.Lys120Asnfs) deletion Pathogenic GRCh37 Chromosome 9, 130423415: 130423415

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 GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.26 AKT3 RPS6KA3 TBC1D7
2 11.12 AKT3 TBC1D7
3 10.78 NFIB NSD1

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 nucleus GO:0005634 9.17 AKT3 FIBP NFIB NSD1 RPS6KA3 SATB2

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

# Name GO ID Score Top Affiliating Genes
1 platelet aggregation GO:0070527 8.62 FIBP STXBP1

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

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 8.8 NFIB NSD1 SATB2

Sources for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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10 dbSNP
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17 ExPASy
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