MCID: MCR237
MIFTS: 27

Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Categories: Genetic 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-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 is EGF/EGFR Signaling Pathway. Affiliated tissues include brain and bone, 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 69)
# Related Disease Score Top Affiliating Genes
1 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 12.5
2 megalencephaly-capillary malformation-polymicrogyria syndrome 12.5
3 megalencephaly 12.5
4 polyhydramnios, megalencephaly, and symptomatic epilepsy 12.3
5 leukoencephalopathy, cystic, without megalencephaly 12.3
6 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 12.3
7 megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 12.2
8 hemimegalencephaly 12.1
9 megalencephaly, autosomal dominant 12.0
10 megalencephaly with dysmyelination 12.0
11 isolated megalencephaly 11.9
12 focal alopecia congenital megalencephaly 11.8
13 rnase t2-deficient leukoencephalopathy 11.8
14 megalencephalic leukoencephalopathy with subcortical cysts 1 11.7
15 cowden syndrome 1 11.4
16 alexander disease 11.4
17 macrocephaly, benign familial 11.2
18 pik3ca-related overgrowth spectrum 11.0
19 neurofaciodigitorenal syndrome 10.8
20 mental retardation, autosomal recessive 34, with variant lissencephaly 10.8
21 early-onset parkinsonism-intellectual disability syndrome 10.8
22 macrocephaly, dysmorphic facies, and psychomotor retardation 10.8
23 polymicrogyria 10.4
24 hydrocephalus 10.3
25 polydactyly 10.3
26 cerebritis 10.1
27 autism 10.0
28 epilepsy 10.0
29 neuronitis 10.0
30 tuberous sclerosis 9.9
31 achondroplasia 9.9
32 thanatophoric dysplasia, type i 9.9
33 alacrima, achalasia, and mental retardation syndrome 9.9
34 periventricular nodular heterotopia 9.9
35 autism spectrum disorder 9.9
36 leukodystrophy 9.9
37 polyhydramnios 9.9
38 cleft palate, isolated 9.7
39 nevus, epidermal 9.7
40 sturge-weber syndrome 9.7
41 tuberous sclerosis 1 9.7
42 ataxia-telangiectasia 9.7
43 canavan disease 9.7
44 sudden infant death syndrome 9.7
45 band heterotopia 9.7
46 polyglucosan body myopathy 1 with or without immunodeficiency 9.7
47 sinusitis 9.7
48 lissencephaly 9.7
49 spastic ataxia 9.7
50 hypogonadotropic hypogonadism 9.7

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
Brain, Bone

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 Likely pathogenic rs587776935 GRCh37 Chromosome 1, 243668598: 243668598
6 AKT3 NM_005465.4(AKT3): c.1393C> T (p.Arg465Trp) single nucleotide variant 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 ARHGAP11A NM_014783.5(ARHGAP11A): c.932G> T (p.Arg311Ile) single nucleotide variant no interpretation for the single variant rs372419991 GRCh38 Chromosome 15, 32628797: 32628797
18 ARHGAP11A NM_014783.5(ARHGAP11A): c.932G> T (p.Arg311Ile) single nucleotide variant no interpretation for the single variant rs372419991 GRCh37 Chromosome 15, 32920998: 32920998
19 ARHGAP11A NM_014783.5(ARHGAP11A): c.1355C> G (p.Ser452Cys) single nucleotide variant no interpretation for the single variant rs146176251 GRCh38 Chromosome 15, 32635787: 32635787
20 ARHGAP11A NM_014783.5(ARHGAP11A): c.1355C> G (p.Ser452Cys) single nucleotide variant no interpretation for the single variant rs146176251 GRCh37 Chromosome 15, 32927988: 32927988
21 TPTE NM_199261.3(TPTE): c.1357-3_1357-2delTA deletion Uncertain significance rs149363218 GRCh37 Chromosome 21, 10910401: 10910402
22 TPTE NM_199261.3(TPTE): c.1357-3_1357-2delTA deletion Uncertain significance rs149363218 GRCh38 Chromosome 21, 10602055: 10602056
23 19p13.12 duplication duplication Likely pathogenic
24 COL11A2 NM_080680.2(COL11A2): c.4559G> A (p.Arg1520His) single nucleotide variant Uncertain significance rs772567850 GRCh37 Chromosome 6, 33133517: 33133517
25 COL11A2 NM_080680.2(COL11A2): c.4559G> A (p.Arg1520His) single nucleotide variant Uncertain significance rs772567850 GRCh38 Chromosome 6, 33165740: 33165740
26 46;XX;ins(3;1)(q23;p22p32)dn Translocation Likely pathogenic
27 46;XY;t(1;3)(q32.1;q13.2)dn Translocation Uncertain significance
28 46;XX;t(2;11)(q11.2;p13)dn Translocation Pathogenic
29 46;XX;t(6;13)(q21;q32)dn Translocation Likely pathogenic
30 46;XY;inv(1)(p11q21)dn inversion Pathogenic
31 46;XX;t(4;14)(p15.2;q13)dn Translocation Likely pathogenic
32 46;XY;t(5;15)(q11.2;q24) Translocation Pathogenic
33 46;XY;t(6;13)(q15;q22.3) Translocation Uncertain significance
34 46;XY;inv(6)(p11.2q25.3) inversion Uncertain significance
35 46;XY;t(6;11)(p12.3;p14.2)dn Translocation Pathogenic
36 46;XX;t(5;17)(p15.31~32;q25.3)dn Translocation Uncertain significance
37 46;XX;t(2;10)(p23;q22.1)dn Translocation Pathogenic
38 46;XY;inv(1)(p22.3p34.1)dn inversion Pathogenic
39 46;XY;t(5;7)(q35;q33)dn Translocation Pathogenic
40 KAT6B NM_012330.3(KAT6B): c.1927A> T (p.Met643Leu) single nucleotide variant Uncertain significance rs778899637 GRCh37 Chromosome 10, 76736022: 76736022
41 KAT6B NM_012330.3(KAT6B): c.1927A> T (p.Met643Leu) single nucleotide variant Uncertain significance rs778899637 GRCh38 Chromosome 10, 74976264: 74976264
42 MT-ND4 NC_012920.1: m.12013A> G single nucleotide variant Uncertain significance rs1057516067 GRCh37 Chromosome MT, 12013: 12013
43 MT-ND4 NC_012920.1: m.12013A> G single nucleotide variant Uncertain significance rs1057516067 GRCh38 Chromosome MT, 12013: 12013
44 MT-ND4 NC_012920.1: m.12018C> G single nucleotide variant Uncertain significance rs1057516068 GRCh37 Chromosome MT, 12018: 12018
45 MT-ND4 NC_012920.1: m.12018C> G single nucleotide variant Uncertain significance rs1057516068 GRCh38 Chromosome MT, 12018: 12018
46 MT-CYB NC_012920.1: m.15246G> A single nucleotide variant Likely pathogenic rs1057516075 GRCh37 Chromosome MT, 15246: 15246
47 MT-CYB NC_012920.1: m.15246G> A single nucleotide variant Likely pathogenic rs1057516075 GRCh38 Chromosome MT, 15246: 15246
48 BTD NM_001281723.2(BTD): c.106_107delGG (p.Gly36Leufs) deletion Uncertain significance rs765906887 GRCh38 Chromosome 3, 15635479: 15635480
49 BTD NM_001281723.2(BTD): c.106_107delGG (p.Gly36Leufs) deletion Uncertain significance rs765906887 GRCh37 Chromosome 3, 15676986: 15676987
50 NFIA NM_001145511.1(NFIA): c.881delG (p.Gly294Glufs) deletion Likely pathogenic rs1057518992 GRCh37 Chromosome 1, 61824905: 61824905

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 10.84 RPS6KA3 STXBP1

GO Terms for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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

Sources for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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