MCEPHAS
MCID: MCR096
MIFTS: 41

Macrocephaly/autism Syndrome (MCEPHAS)

Categories: Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Macrocephaly/autism Syndrome

MalaCards integrated aliases for Macrocephaly/autism Syndrome:

Name: Macrocephaly/autism Syndrome 56 73 29 13 6 39 71
Macrocephaly-Intellectual Disability-Autism Syndrome 12 58
Macrocephaly-Autism Syndrome 12 15
Mcephas 73

Characteristics:

Orphanet epidemiological data:

58
macrocephaly-intellectual disability-autism syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
macrocephaly/autism syndrome:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060867
OMIM 56 605309
UMLS via Orphanet 72 C1854416
Orphanet 58 ORPHA210548
MedGen 41 C1854416
UMLS 71 C1854416

Summaries for Macrocephaly/autism Syndrome

OMIM : 56 Macrocephaly/autism syndrome is an autosomal dominant disorder characterized by increased head circumference, abnormal facial features, and delayed psychomotor development resulting in autistic behavior or mental retardation (Herman et al., 2007). Some patients may have a primary immunodeficiency disorder with recurrent infections associated with variably abnormal T- and B-cell function (Tsujita et al., 2016). (605309)

MalaCards based summary : Macrocephaly/autism Syndrome, also known as macrocephaly-intellectual disability-autism syndrome, is related to autism and vacterl association with hydrocephalus. An important gene associated with Macrocephaly/autism Syndrome is PTEN (Phosphatase And Tensin Homolog), and among its related pathways/superpathways are mTOR signaling pathway (KEGG) and PI3K / Akt Signaling. Affiliated tissues include b cells, t cells and brain, and related phenotypes are splenomegaly and hepatomegaly

Disease Ontology : 12 A syndrome characterized by macrocephaly, facial phenotypes including square outline with frontal bossing, 'dished-out' midface, biparietal narrowing, and long philtrum, developmental delay and autism that has material basis in heterozygous mutation in the PTEN gene on chromosome 10q23.

UniProtKB/Swiss-Prot : 73 Macrocephaly/autism syndrome: Patients have autism spectrum disorders and macrocephaly, with head circumferences ranging from +2.5 to +8 SD for age and sex (average head circumference +4.0 SD).

Related Diseases for Macrocephaly/autism Syndrome

Diseases related to Macrocephaly/autism Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 autism 28.2 PTEN NLGN2 NLGN1 HEPACAM DEPDC5
2 vacterl association with hydrocephalus 10.1 PTEN KLLN
3 vacterl association 10.1 PTEN KLLN
4 autism spectrum disorder 10.1
5 glioma susceptibility 2 10.1 PTEN KLLN
6 schizophrenia 13 9.9 NPRL3 DEPDC5
7 epilepsy, familial focal, with variable foci 1 9.8 NPRL3 DEPDC5
8 cowden syndrome 9.6 PTEN NLGN1 KLLN
9 childhood disintegrative disease 9.5 NLGN2 NLGN1
10 phelan-mcdermid syndrome 9.2 NLGN2 NLGN1
11 pervasive developmental disorder 9.1 PTEN NLGN2 NLGN1

Graphical network of the top 20 diseases related to Macrocephaly/autism Syndrome:



Diseases related to Macrocephaly/autism Syndrome

Symptoms & Phenotypes for Macrocephaly/autism Syndrome

Human phenotypes related to Macrocephaly/autism Syndrome:

31 (show all 16)
# Description HPO Frequency HPO Source Accession
1 splenomegaly 31 very rare (1%) HP:0001744
2 hepatomegaly 31 very rare (1%) HP:0002240
3 decreased antibody level in blood 31 very rare (1%) HP:0004313
4 lymphopenia 31 very rare (1%) HP:0001888
5 recurrent infections 31 very rare (1%) HP:0002719
6 obesity 31 HP:0001513
7 frontal bossing 31 HP:0002007
8 intellectual disability 31 HP:0001249
9 global developmental delay 31 HP:0001263
10 depressed nasal bridge 31 HP:0005280
11 short nose 31 HP:0003196
12 long philtrum 31 HP:0000343
13 biparietal narrowing 31 HP:0004422
14 autism 31 HP:0000717
15 broad forehead 31 HP:0000337
16 postnatal macrocephaly 31 HP:0005490

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Face:
frontal bossing
long philtrum
broad forehead
square outline
'dished out' midface

Head And Neck Head:
biparietal narrowing
macrocephaly, postnatal

Neurologic Central Nervous System:
developmental delay
mental retardation

Abdomen Liver:
hepatomegaly (in some patients)

Growth Weight:
obesity (in some patients)

Head And Neck Nose:
depressed nasal bridge
short nose

Neurologic Behavioral Psychiatric Manifestations:
autism

Immunology:
recurrent infections (in some patients)
primary immunodeficiency (in some patients)
opportunistic infections (in some patients)
hypogammaglobulinemia (in some patients)
lymphopenia (in some patients)
more
Abdomen Spleen:
splenomegaly (in some patients)

Clinical features from OMIM:

605309

Drugs & Therapeutics for Macrocephaly/autism Syndrome

Search Clinical Trials , NIH Clinical Center for Macrocephaly/autism Syndrome

Genetic Tests for Macrocephaly/autism Syndrome

Genetic tests related to Macrocephaly/autism Syndrome:

# Genetic test Affiliating Genes
1 Macrocephaly/autism Syndrome 29 PTEN

Anatomical Context for Macrocephaly/autism Syndrome

MalaCards organs/tissues related to Macrocephaly/autism Syndrome:

40
B Cells, T Cells, Brain, Cortex, Thyroid, Breast, Testes

Publications for Macrocephaly/autism Syndrome

Articles related to Macrocephaly/autism Syndrome:

(show all 20)
# Title Authors PMID Year
1
Phosphatase and tensin homolog (PTEN) mutation can cause activated phosphatidylinositol 3-kinase δ syndrome-like immunodeficiency. 56 6
27426521 2016
2
Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. 56 6
23160955 2012
3
Increasing knowledge of PTEN germline mutations: Two additional patients with autism and macrocephaly. 56 6
17286265 2007
4
Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations. 56 6
15805158 2005
5
Pten Mutations Alter Brain Growth Trajectory and Allocation of Cell Types through Elevated β-Catenin Signaling. 56
26180201 2015
6
Decreased aggression and increased repetitive behavior in Pten haploinsufficient mice. 56
25561290 2015
7
Pten haploinsufficient mice show broad brain overgrowth but selective impairments in autism-relevant behavioral tests. 56
24497577 2014
8
Haploinsufficiency for Pten and Serotonin transporter cooperatively influences brain size and social behavior. 56
19208814 2009
9
Pten regulates neuronal arborization and social interaction in mice. 56
16675393 2006
10
Cole-Hughes macrocephaly syndrome and associated autistic manifestations. 56
10982971 2000
11
Germline PTEN mutation in a family with Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. 6
9856571 1998
12
Germline mutations in PTEN are present in Bannayan-Zonana syndrome. 6
9241266 1997
13
Germline mutations in the PTEN/MMAC1 gene in patients with Cowden disease. 6
9259288 1997
14
Autism and macrocephaly. 56
9193390 1997
15
Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome. 6
9140396 1997
16
Autosomal dominant macrocephaly: benign familial macrocephaly or a new syndrome? 56
1719811 1991
17
Genetic Suppression of mTOR Rescues Synaptic and Social Behavioral Abnormalities in a Mouse Model of Pten Haploinsufficiency. 61
31441226 2019
18
A novel missense PTEN mutation identified in a patient with macrocephaly and developmental delay. 61
31149344 2019
19
Hyperconnectivity of prefrontal cortex to amygdala projections in a mouse model of macrocephaly/autism syndrome. 61
27845329 2016
20
Mental deficiency, alterations in performance, and CNS abnormalities in overgrowth syndromes. 61
12561058 2003

Variations for Macrocephaly/autism Syndrome

ClinVar genetic disease variations for Macrocephaly/autism Syndrome:

6 (show all 39) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 PTEN NM_000314.7(PTEN):c.517C>T (p.Arg173Cys)SNV Pathogenic 189500 rs121913293 10:89711899-89711899 10:87952142-87952142
2 PTEN NM_000314.7(PTEN):c.1048dup (p.Thr350fs)duplication Pathogenic 209187 rs797045066 10:89725060-89725061 10:87965303-87965304
3 PTEN NM_000314.7(PTEN):c.900del (p.Ile300fs)deletion Pathogenic 211972 rs797045904 10:89720749-89720749 10:87960992-87960992
4 PTEN NM_000314.7(PTEN):c.697C>T (p.Arg233Ter)SNV Pathogenic 7813 rs121909219 10:89717672-89717672 10:87957915-87957915
5 PTEN NM_000314.7(PTEN):c.388C>T (p.Arg130Ter)SNV Pathogenic 7819 rs121909224 10:89692904-89692904 10:87933147-87933147
6 PTEN NM_000314.7(PTEN):c.640C>T (p.Gln214Ter)SNV Pathogenic 7827 rs121909227 10:89717615-89717615 10:87957858-87957858
7 PTEN NM_000314.7(PTEN):c.1003C>T (p.Arg335Ter)SNV Pathogenic 7833 rs121909231 10:89720852-89720852 10:87961095-87961095
8 PTEN NM_000314.7(PTEN):c.278A>G (p.His93Arg)SNV Pathogenic 7848 rs121909238 10:89692794-89692794 10:87933037-87933037
9 PTEN PTEN, 1-BP INS, 519Tinsertion Pathogenic 7851
10 PTEN NM_001304718.2(PTEN):c.-359C>TSNV Pathogenic 39669 rs397514560 10:89692908-89692908 10:87933151-87933151
11 PTEN NM_001304718.2(PTEN):c.-346dupduplication Pathogenic 39670 rs398123323 10:89692920-89692921 10:87933163-87933164
12 PTEN NM_000314.7(PTEN):c.959T>G (p.Leu320Ter)SNV Pathogenic 428253 rs1114167667 10:89720808-89720808 10:87961051-87961051
13 PTEN NM_001304718.2(PTEN):c.-664_-663GA[3]short repeat Pathogenic 393298 rs1057524874 10:89624267-89624268 10:87864510-87864511
14 PTEN NM_000314.7(PTEN):c.253+2T>ASNV Pathogenic/Likely pathogenic 468676 rs1224040268 10:89690848-89690848 10:87931091-87931091
15 PTEN NM_000314.7(PTEN):c.860C>G (p.Ser287Ter)SNV Pathogenic/Likely pathogenic 216987 rs863224909 10:89720709-89720709 10:87960952-87960952
16 PTEN NM_000314.7(PTEN):c.740T>C (p.Leu247Ser)SNV Likely pathogenic 223142 rs1057519368 10:89717715-89717715 10:87957958-87957958
17 PTEN NM_001304718.2(PTEN):c.-92C>ASNV Likely pathogenic 39668 rs397514559 10:89711882-89711882 10:87952125-87952125
18 PTEN NM_000314.7(PTEN):c.755A>G (p.Asp252Gly)SNV Likely pathogenic 7849 rs121909239 10:89717730-89717730 10:87957973-87957973
19 PTEN NM_000314.7(PTEN):c.722T>C (p.Phe241Ser)SNV Likely pathogenic 7850 rs121909240 10:89717697-89717697 10:87957940-87957940
20 PTEN NM_000314.6(PTEN):c.866_867insGA (p.Val290Lysfs)insertion Likely pathogenic 560715 rs1564568303 10:89720714-89720715 10:87960957-87960958
21 PTEN NM_001304717.5(PTEN):c.1322-1G>ASNV Likely pathogenic 689447 10:89720650-89720650 10:87960893-87960893
22 PTEN NM_000314.7(PTEN):c.404T>A (p.Ile135Lys)SNV Likely pathogenic 428235 rs370795352 10:89692920-89692920 10:87933163-87933163
23 PTEN NM_000314.7(PTEN):c.947T>C (p.Leu316Pro)SNV Conflicting interpretations of pathogenicity 418653 rs1064793345 10:89720796-89720796 10:87961039-87961039
24 PTEN NM_000314.7(PTEN):c.470A>G (p.Glu157Gly)SNV Conflicting interpretations of pathogenicity 427593 rs1085308051 10:89692986-89692986 10:87933229-87933229
25 PTEN NM_000314.7(PTEN):c.862G>A (p.Glu288Lys)SNV Uncertain significance 484603 rs1554825528 10:89720711-89720711 10:87960954-87960954
26 PTEN NM_001126049.1(KLLN):c.-736G>CSNV Uncertain significance 488964 rs1554889801 10:89622980-89622980 10:87863223-87863223
27 PTEN NM_001126049.1(KLLN):c.-792C>TSNV Uncertain significance 127663 rs587779982 10:89623036-89623036 10:87863279-87863279
28 PTEN NM_000314.7(PTEN):c.-834C>TSNV Uncertain significance 127676 rs587779994 10:89623392-89623392 10:87863635-87863635
29 PTEN NM_000314.4(PTEN):c.-943C>TSNV Uncertain significance 127682 rs587779999 10:89623283-89623283 10:87863526-87863526
30 PTEN NM_000314.7(PTEN):c.882T>G (p.Ser294Arg)SNV Uncertain significance 127693 rs143335584 10:89720731-89720731 10:87960974-87960974
31 PTEN NM_000314.7(PTEN):c.914G>A (p.Ser305Asn)SNV Uncertain significance 127696 rs587780007 10:89720763-89720763 10:87961006-87961006
32 PTEN NM_000314.7(PTEN):c.892C>G (p.Gln298Glu)SNV Uncertain significance 127695 rs371387815 10:89720741-89720741 10:87960984-87960984
33 PTEN NM_000314.4(PTEN):c.-868G>CSNV Uncertain significance 141949 rs587782133 10:89623358-89623358 10:87863601-87863601
34 PTEN NM_001126049.1(KLLN):c.-828C>TSNV Uncertain significance 187362 rs786203674 10:89623072-89623072 10:87863315-87863315
35 PTEN NM_000314.7(PTEN):c.545T>C (p.Leu182Ser)SNV Uncertain significance 187827 rs794729664 10:89711927-89711927 10:87952170-87952170
36 PTEN NM_000314.7(PTEN):c.-665G>ASNV Uncertain significance 189528 rs553371022 10:89623561-89623561 10:87863804-87863804
37 PTEN NM_000314.7(PTEN):c.-821G>TSNV Uncertain significance 234510 rs587779993 10:89623405-89623405 10:87863648-87863648
38 PTEN NM_000314.7(PTEN):c.-764G>ASNV Uncertain significance 7844 rs587776674 10:89623462-89623462 10:87863705-87863705
39 PTEN NM_000314.7(PTEN):c.235G>A (p.Ala79Thr)SNV Likely benign 41682 rs202004587 10:89690828-89690828 10:87931071-87931071

UniProtKB/Swiss-Prot genetic disease variations for Macrocephaly/autism Syndrome:

73
# Symbol AA change Variation ID SNP ID
1 PTEN p.His93Arg VAR_032634 rs121909238
2 PTEN p.Phe241Ser VAR_032636 rs121909240
3 PTEN p.Asp252Gly VAR_032637 rs121909239
4 PTEN p.Thr131Ile VAR_076762 rs397514560
5 PTEN p.Thr167Asn VAR_076763 rs397514559

Expression for Macrocephaly/autism Syndrome

Search GEO for disease gene expression data for Macrocephaly/autism Syndrome.

Pathways for Macrocephaly/autism Syndrome

Pathways related to Macrocephaly/autism Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.39 PTEN NPRL3 MAPKAP1 DEPDC5
2 10.92 PTEN MAPKAP1

GO Terms for Macrocephaly/autism Syndrome

Cellular components related to Macrocephaly/autism Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 postsynaptic membrane GO:0045211 9.43 PTEN NLGN2 NLGN1
2 integral component of postsynaptic membrane GO:0099055 9.32 NLGN2 NLGN1
3 integral component of postsynaptic specialization membrane GO:0099060 9.16 NLGN2 NLGN1
4 spanning component of membrane GO:0089717 8.96 NLGN2 NLGN1
5 GATOR1 complex GO:1990130 8.62 NPRL3 DEPDC5

Biological processes related to Macrocephaly/autism Syndrome according to GeneCards Suite gene sharing:

(show all 25)
# Name GO ID Score Top Affiliating Genes
1 modulation of chemical synaptic transmission GO:0050804 9.62 NLGN2 NLGN1
2 positive regulation of synapse assembly GO:0051965 9.62 NLGN2 NLGN1
3 long-term synaptic potentiation GO:0060291 9.61 PTEN NLGN1
4 synapse organization GO:0050808 9.61 NLGN2 NLGN1
5 cellular response to amino acid starvation GO:0034198 9.6 NPRL3 DEPDC5
6 synaptic vesicle endocytosis GO:0048488 9.59 NLGN2 NLGN1
7 negative regulation of TOR signaling GO:0032007 9.58 NPRL3 DEPDC5
8 regulation of AMPA receptor activity GO:2000311 9.58 NLGN2 NLGN1
9 positive regulation of synaptic transmission, glutamatergic GO:0051968 9.57 NLGN2 NLGN1
10 cardiac muscle tissue development GO:0048738 9.56 PTEN NPRL3
11 neuron cell-cell adhesion GO:0007158 9.55 NLGN2 NLGN1
12 presynapse assembly GO:0099054 9.54 NLGN2 NLGN1
13 protein localization to synapse GO:0035418 9.52 NLGN2 NLGN1
14 regulation of respiratory gaseous exchange by neurological system process GO:0002087 9.51 NLGN2 NLGN1
15 synapse assembly GO:0007416 9.5 PTEN NLGN2 NLGN1
16 positive regulation of synaptic transmission, GABAergic GO:0032230 9.49 NLGN2 NLGN1
17 postsynaptic membrane assembly GO:0097104 9.48 NLGN2 NLGN1
18 negative regulation of dendritic spine morphogenesis GO:0061002 9.46 PTEN NLGN1
19 postsynaptic density protein 95 clustering GO:0097119 9.43 NLGN2 NLGN1
20 positive regulation of synaptic vesicle clustering GO:2000809 9.4 NLGN2 NLGN1
21 positive regulation of protein localization to synapse GO:1902474 9.37 NLGN2 NLGN1
22 postsynaptic specialization assembly GO:0098698 9.26 NLGN2 NLGN1
23 terminal button organization GO:0072553 9.16 NLGN2 NLGN1
24 positive regulation of excitatory postsynaptic potential GO:2000463 9.13 PTEN NLGN2 NLGN1
25 presynaptic membrane assembly GO:0097105 8.8 PTEN NLGN2 NLGN1

Molecular functions related to Macrocephaly/autism Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 PDZ domain binding GO:0030165 9.16 PTEN NLGN1
2 cell adhesion molecule binding GO:0050839 8.96 NLGN2 NLGN1
3 neurexin family protein binding GO:0042043 8.62 NLGN2 NLGN1

Sources for Macrocephaly/autism Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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