Macrocephaly/megalencephaly Syndrome, Autosomal Recessive disease: Malacards - Research Articles, Drugs, Genes, Clinical Trials

MCID: MCR237 MIFTS: 27	Macrocephaly/megalencephaly Syndrome, Autosomal Recessive Categories: Genetic diseases
Genes Variations Tissues Related diseases Pathways Symptoms & Phenotypes Download Expand all tables

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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:

MalaCards categories:
Global: Genetic diseases

See all MalaCards categories (disease lists)

External Ids:

OMIM ⁵⁷ 248000

MedGen ⁴² C3806412

MeSH ⁴⁴ D058627

UMLS ⁷³ C3806412

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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.

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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
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:

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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

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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

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Genetic Tests for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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Anatomical Context for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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

⁴¹

Brain, Bone

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Publications for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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Genes for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

Genes related to Macrocephaly/megalencephaly Syndrome, Autosomal Recessive (4 elite genes):

- Elite gene

- Cancer Census gene in COSMIC

#	Symbol	Description	Category	Score	Evidence	PubmedIds
1	TBC1D7	TBC1 Domain Family Member 7	Protein Coding	918.32	Molecular basis known ⁵⁷ Pathogenic ⁶ GeneCards inferred via : Disorders (show sections)	23687350 24515783
2	STXBP1	Syntaxin Binding Protein 1	Protein Coding	400	Pathogenic ⁶
3	SATB2	SATB Homeobox 2	Protein Coding	400	Pathogenic ⁶
4	RPS6KA3	Ribosomal Protein S6 Kinase A3	Protein Coding	400	Pathogenic ⁶
5	NSD1	Nuclear Receptor Binding SET Domain Protein 1	Protein Coding	25	Pathogenic/Likely pathogenic ⁶
6	FIBP	FGF1 Intracellular Binding Protein	Protein Coding	25	Pathogenic/Likely pathogenic ⁶

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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

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Expression for Macrocephaly/megalencephaly Syndrome, Autosomal Recessive

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

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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	EGF/EGFR Signaling Pathway ¹	10.84	RPS6KA3 STXBP1

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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

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