PGS
MCID: PTT059
MIFTS: 49

Pettigrew Syndrome (PGS)

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

Aliases & Classifications for Pettigrew Syndrome

MalaCards integrated aliases for Pettigrew Syndrome:

Name: Pettigrew Syndrome 56 12 52 73 29 13 6
X-Linked Intellectual Disability-Dandy-Walker Malformation-Basal Ganglia Disease-Seizures Syndrome 12 52 58
Mrxs21 56 12 73
Mrxs5 56 52 73
Mrx59 56 12 73
Pgs 56 52 73
Syndromic X-Linked Intellectual Disability 5 12 15
Mental Retardation, X-Linked, Syndromic 5 56 43
Mental Retardation, X-Linked Syndromic 5 56 12
Mental Retardation X-Linked Syndromic 5 52 73
Fried Syndrome 12 58
Mrxsf 56 73
Mental Retardation, X-Linked, with Dandy-Walker Malformation, Basal Ganglia Disease, and Seizures 56
X-Linked Intellectual Disability - Dandy-Walker Malformation - Basal Ganglia Disease - Seizures 52
Mental Retardation X-Linked with Dandy-Walker Malformation, Basal Ganglia Disease, and Seizures 73
X-Linked Metal Retardation with Dandy-Walker Malformation, Basal Ganglia Disease, and Seizures 12
Mental Retardation X-Linked with Dandy-Walker Malformation Basal Ganglia Disease and Seizures 52
Dandy-Walker Malformation with Intellectual Disability, Basal Ganglia Disease and Seizures 52
X-Linked Intellectual Disability-Hypotonia-Facial Dysmorphism-Aggressive Behavior Syndrome 58
Dandy-Walker Malformation with Mental Retardation, Basal Ganglia Disease, and Seizures 71
Mental Retardation, X-Linked, Syndromic, Fried Type; Mrxsf 56
Mental Retardation, X-Linked, Syndromic, Fried Type 56
Mental Retardation, X-Linked, Syndromic 21; Mrxs21 56
Mental Retardation, X-Linked Syndromic, Fried Type 39
Mental Retardation, X-Linked, Syndromic 5; Mrxs5 56
Syndromic X-Linked Mental Retardation Fried Type 12
Mental Retardation X-Linked Syndromic Fried Type 73
Mental Retardation, X-Linked, Syndromic 21 56
Syndromic X-Linked Mental Retardation 21 12
Mental Retardation X-Linked Syndromic 21 73
Mental Retardation, X-Linked 59; Mrx59 56
Mental Retardation, X-Linked 59 71

Characteristics:

Orphanet epidemiological data:

58
x-linked intellectual disability-dandy-walker malformation-basal ganglia disease-seizures syndrome
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal;
x-linked intellectual disability-hypotonia-facial dysmorphism-aggressive behavior syndrome
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;
fried syndrome
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Miscellaneous:
onset in infancy
additional features are variably present

Inheritance:
x-linked recessive


HPO:

31
pettigrew syndrome:
Inheritance x-linked inheritance x-linked recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Developmental anomalies during embryogenesis


Summaries for Pettigrew Syndrome

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 1568 Definition X-linked Dandy-Walker malformation with intellectual disability , basal ganglia disease and seizures (XDIBS), or Pettigrew syndrome is a central nervous system malformation characterized by severe intellectual deficit, early hypotonia with progression to spasticity and contractures , choreoathetosis, seizures, dysmorphic face (long face with prominent forehead), and brain imaging abnormalities such as Dandy-Walker malformation (see this term), and iron deposition. Visit the Orphanet disease page for more resources.

MalaCards based summary : Pettigrew Syndrome, also known as x-linked intellectual disability-dandy-walker malformation-basal ganglia disease-seizures syndrome, is related to pemphigoid gestationis and glucagonoma, and has symptoms including seizures, gait ataxia and muscle spasticity. An important gene associated with Pettigrew Syndrome is AP1S2 (Adaptor Related Protein Complex 1 Subunit Sigma 2), and among its related pathways/superpathways are Human cytomegalovirus infection and Delta508-CFTR traffic / ER-to-Golgi in CF. Affiliated tissues include brain, eye and cerebellum, and related phenotypes are global developmental delay and inguinal hernia

Disease Ontology : 12 A syndromic X-linked intellectual disability characterized by intellectual disability and variable features including; choreoathetosis, hydrocephalus, Dandy-Walker malformation, seizures, and iron or calcium deposition in the brain that has material basis in mutation in the AP1S2 gene on chromosome Xp22.

OMIM : 56 Pettigrew syndrome is characterized by mental retardation and highly variable additional features, including choreoathetosis, hydrocephalus, Dandy-Walker malformation, seizures, and iron or calcium deposition in the brain, both between and within families (summary by Cacciagli et al., 2014). See 311510 for another X-linked mental retardation syndrome associated with basal ganglia disease (Waisman syndrome). See 220219 for another mental retardation syndrome with Dandy-Walker malformation. (304340)

UniProtKB/Swiss-Prot : 73 Pettigrew syndrome: A syndrome characterized by mental retardation and additional highly variable features, including choreoathetosis, hydrocephalus, Dandy- Walker malformation, seizures, and iron or calcium deposition in the brain. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.

Related Diseases for Pettigrew Syndrome

Diseases related to Pettigrew Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 184)
# Related Disease Score Top Affiliating Genes
1 pemphigoid gestationis 11.8
2 glucagonoma 11.4
3 aromatase deficiency 11.2
4 primary pigmented nodular adrenocortical disease 11.2
5 phacolytic glaucoma 11.2
6 pyoderma 10.3
7 pyoderma gangrenosum 10.3
8 hair whorl 10.2
9 lung cancer 10.2
10 periodontitis 10.2
11 gastric cancer 10.1
12 bone resorption disease 10.1
13 dandy-walker syndrome 10.1
14 alacrima, achalasia, and mental retardation syndrome 10.1
15 visual epilepsy 10.1
16 basal ganglia disease 10.1
17 seizure disorder 10.1
18 hypertension, essential 10.1
19 allergic rhinitis 10.1
20 primary hyperparathyroidism 10.1
21 lyme disease 10.1
22 pathological gambling 10.1
23 hyperparathyroidism 10.1
24 rhinitis 10.1
25 peptic ulcer disease 10.1
26 breast cancer 10.0
27 triiodothyronine receptor auxiliary protein 10.0
28 periodontitis, chronic 10.0
29 cervical cancer 10.0
30 ovarian hyperstimulation syndrome 10.0
31 acute promyelocytic leukemia 10.0
32 pain agnosia 10.0
33 adenoid cystic carcinoma 10.0
34 gastroparesis 10.0
35 diarrhea 10.0
36 amenorrhea 10.0
37 duodenal ulcer 10.0
38 astrocytoma 10.0
39 fibrosarcoma 10.0
40 gastritis 10.0
41 liver disease 10.0
42 ovarian cyst 10.0
43 kidney disease 10.0
44 end stage renal disease 10.0
45 vasculitis 10.0
46 atrophic gastritis 10.0
47 cervix uteri carcinoma in situ 10.0
48 acute myocardial infarction 10.0
49 48,xyyy 10.0
50 cervical intraepithelial neoplasia 10.0

Graphical network of the top 20 diseases related to Pettigrew Syndrome:



Diseases related to Pettigrew Syndrome

Symptoms & Phenotypes for Pettigrew Syndrome

Human phenotypes related to Pettigrew Syndrome:

58 31 (show top 50) (show all 60)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001263
2 inguinal hernia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000023
3 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
4 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000256
5 hydrocephalus 58 31 occasional (7.5%) Very frequent (99-80%) HP:0000238
6 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
7 gait disturbance 58 31 hallmark (90%) Very frequent (99-80%),Frequent (79-30%) HP:0001288
8 feeding difficulties 58 31 hallmark (90%) Very frequent (99-80%) HP:0011968
9 skeletal muscle atrophy 58 31 hallmark (90%) Very frequent (99-80%),Occasional (29-5%) HP:0003202
10 strabismus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000486
11 cryptorchidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000028
12 cerebral cortical atrophy 58 31 hallmark (90%) Very frequent (99-80%) HP:0002120
13 open mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000194
14 aplasia/hypoplasia of the cerebellum 58 31 hallmark (90%) Very frequent (99-80%) HP:0007360
15 long face 58 31 hallmark (90%) Very frequent (99-80%),Frequent (79-30%) HP:0000276
16 protruding ear 58 31 hallmark (90%) Very frequent (99-80%) HP:0000411
17 ventriculomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002119
18 intellectual disability, moderate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002342
19 high forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000348
20 cerebral calcification 58 31 occasional (7.5%) Very frequent (99-80%) HP:0002514
21 triangular face 58 31 hallmark (90%) Very frequent (99-80%) HP:0000325
22 long nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0003189
23 intellectual disability, profound 58 31 hallmark (90%) Very frequent (99-80%) HP:0002187
24 spastic diplegia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001264
25 aggressive behavior 58 31 hallmark (90%) Very frequent (99-80%),Frequent (79-30%) HP:0000718
26 generalized hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001290
27 poor speech 58 31 hallmark (90%) Very frequent (99-80%) HP:0002465
28 short chin 58 31 hallmark (90%) Very frequent (99-80%) HP:0000331
29 coarse facial features 58 31 frequent (33%) Frequent (79-30%) HP:0000280
30 macrotia 58 31 frequent (33%) Frequent (79-30%) HP:0000400
31 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
32 eeg abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0002353
33 myopathy 58 31 frequent (33%) Frequent (79-30%) HP:0003198
34 high palate 58 31 frequent (33%) Frequent (79-30%) HP:0000218
35 short philtrum 58 31 frequent (33%) Frequent (79-30%) HP:0000322
36 autistic behavior 58 31 frequent (33%) Frequent (79-30%) HP:0000729
37 hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000365
38 thickened calvaria 58 31 occasional (7.5%) Occasional (29-5%) HP:0002684
39 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
40 abnormal cerebellum morphology 58 31 occasional (7.5%) Occasional (29-5%) HP:0001317
41 abnormality of the optic nerve 58 31 occasional (7.5%) Occasional (29-5%) HP:0000587
42 dandy-walker malformation 31 occasional (7.5%) HP:0001305
43 mandibular prognathia 31 HP:0000303
44 abnormal facial shape 58 Very frequent (99-80%)
45 thick vermilion border 31 HP:0012471
46 sensorineural hearing impairment 31 HP:0000407
47 flexion contracture 31 HP:0001371
48 spasticity 31 HP:0001257
49 intellectual disability, severe 31 HP:0010864
50 prominent forehead 31 HP:0011220

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Face:
coarse facial features
prominent forehead
long face
prominent jaw

Neurologic Central Nervous System:
seizures
spasticity
choreoathetosis
mental retardation, severe
ataxic gait
more
Neurologic Behavioral Psychiatric Manifestations:
self-injurious behavior

Head And Neck Eyes:
deep-set eyes

Skeletal:
joint contractures

Skeletal Spine:
scoliosis

Neurologic Peripheral Nervous System:
hyperreflexia

Muscle Soft Tissue:
hypotonia

Head And Neck Mouth:
large mouth
full lips

Head And Neck Nose:
large nose

Clinical features from OMIM:

304340

UMLS symptoms related to Pettigrew Syndrome:


seizures, gait ataxia, muscle spasticity

Drugs & Therapeutics for Pettigrew Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Search for Fragility Indicators Among People Aged 50+ With Chronic HIV Infection Unknown status NCT02874118

Search NIH Clinical Center for Pettigrew Syndrome

Cochrane evidence based reviews: mental retardation, x-linked, syndromic 5

Genetic Tests for Pettigrew Syndrome

Genetic tests related to Pettigrew Syndrome:

# Genetic test Affiliating Genes
1 Pettigrew Syndrome 29 AP1S2

Anatomical Context for Pettigrew Syndrome

MalaCards organs/tissues related to Pettigrew Syndrome:

40
Brain, Eye, Cerebellum, Skeletal Muscle

Publications for Pettigrew Syndrome

Articles related to Pettigrew Syndrome:

(show all 13)
# Title Authors PMID Year
1
AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome). 6 61 56
23756445 2014
2
Mutations in the AP1S2 gene encoding the sigma 2 subunit of the adaptor protein 1 complex are associated with syndromic X-linked mental retardation with hydrocephalus and calcifications in basal ganglia. 56 6
17617514 2007
3
Mutations in the gene encoding the Sigma 2 subunit of the adaptor protein 1 complex, AP1S2, cause X-linked mental retardation. 6 56
17186471 2006
4
Syndromic form of X-linked mental retardation with marked hypotonia in early life, severe mental handicap, and difficult adult behavior maps to Xp22. 6 56
12599187 2003
5
Regional localization of a nonspecific X-linked mental retardation gene (MRX59) to Xp21.2-p22.2. 6 56
10398241 1999
6
New X-linked mental retardation disorder with Dandy-Walker malformation, basal ganglia disease, and seizures. 6 56
2018058 1991
7
X-linked mental retardation and-or hydrocephalus. 6 56
5054319 1972
8
A systematic, large-scale resequencing screen of X-chromosome coding exons in mental retardation. 56
19377476 2009
9
X-linked inheritance of Dandy-Walker variant. 56
11822699 2002
10
Prenatal diagnosis of Dandy-Walker malformation in a family displaying X-linked inheritance. 56
8464840 1993
11
Linkage of the gene for an X-linked mental retardation disorder to a hypervariable (AGAT)n repeat motif within the human hypoxanthine phosphoribosyltransferase (HPRT) locus (Xq26). 56
1746558 1991
12
Possible linkage between Xg and the locus for a gene causing mental retardation with or without hydrocephalus. 56
4697849 1973
13
A novel splice site mutation in AP1S2 gene for X-linked mental retardation in a Chinese pedigree and literature review. 61
30714330 2019

Variations for Pettigrew Syndrome

ClinVar genetic disease variations for Pettigrew Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 AP1S2 NM_001272071.2(AP1S2):c.281del (p.Phe94fs)deletion Pathogenic 434219 rs1555904182 X:15864033-15864033 X:15845910-15845910
2 AP1S2 NM_001272071.2(AP1S2):c.106C>T (p.Gln36Ter)SNV Pathogenic 10777 rs104894739 X:15870542-15870542 X:15852419-15852419
3 AP1S2 NM_001272071.2(AP1S2):c.154C>T (p.Arg52Ter)SNV Pathogenic 10778 rs104894735 X:15870494-15870494 X:15852371-15852371
4 AP1S2 NM_001272071.2(AP1S2):c.180-5_180-2deldeletion Pathogenic 10779 rs587776738 X:15864136-15864139 X:15846013-15846016
5 AP1S2 NM_001272071.2(AP1S2):c.288+5G>ASNV Pathogenic 10780 rs587776739 X:15864021-15864021 X:15845898-15845898
6 AP1S2 NM_001272071.2(AP1S2):c.226G>T (p.Glu76Ter)SNV Pathogenic 10781 rs137852213 X:15864088-15864088 X:15845965-15845965
7 AP1S2 NM_001272071.2(AP1S2):c.426+1G>TSNV Pathogenic 140457 rs587777542 X:15863501-15863501 X:15845378-15845378
8 AP1S2 NM_001272071.2(AP1S2):c.1-3C>ASNV Pathogenic 397541 rs1060499672 X:15870650-15870650 X:15852527-15852527
9 CUL4B NM_003588.3(CUL4B):c.2687G>A (p.Arg896Gln)SNV Likely pathogenic 434871 rs1556173896 X:119660671-119660671 X:120526816-120526816

Expression for Pettigrew Syndrome

Search GEO for disease gene expression data for Pettigrew Syndrome.

Pathways for Pettigrew Syndrome

Pathways related to Pettigrew Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.53 CUL4B CALML4 AP1S2 AP1S1 AP1M2 AP1M1
2
Show member pathways
12.13 AP1S2 AP1S1 AP1M2 AP1M1
3
Show member pathways
12.05 AP1S2 AP1S1 AP1M2 AP1M1
4 11.73 AP1S2 AP1S1 AP1M2 AP1M1
5 11.47 AP1S2 AP1S1 AP1M2 AP1M1
6
Show member pathways
11.2 AP1S2 AP1S1 AP1M2 AP1M1
7 10.78 AP1S2 AP1S1 AP1M2 AP1M1

GO Terms for Pettigrew Syndrome

Cellular components related to Pettigrew Syndrome according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 Golgi membrane GO:0000139 9.73 AP1S2 AP1S1 AP1M2 AP1M1
2 cytoplasmic vesicle GO:0031410 9.63 SYT6 PALM AP1S2 AP1S1 AP1M2 AP1M1
3 cytoplasmic vesicle membrane GO:0030659 9.56 AP1S2 AP1S1 AP1M2 AP1M1
4 clathrin-coated vesicle GO:0030136 9.49 AP1M2 AP1M1
5 clathrin-coated pit GO:0005905 9.48 AP1S2 AP1S1
6 clathrin-coated vesicle membrane GO:0030665 9.46 AP1M2 AP1M1
7 membrane coat GO:0030117 9.4 AP1S2 AP1S1
8 clathrin adaptor complex GO:0030131 9.37 AP1M2 AP1M1
9 lysosomal membrane GO:0005765 9.35 AP5B1 AP1S2 AP1S1 AP1M2 AP1M1
10 AP-type membrane coat adaptor complex GO:0030119 9.32 AP5B1 AP1S2
11 trans-Golgi network membrane GO:0032588 8.92 AP1S2 AP1S1 AP1M2 AP1M1

Biological processes related to Pettigrew Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein transport GO:0015031 9.65 AP5B1 AP1S2 AP1S1 AP1M2 AP1M1
2 intracellular protein transport GO:0006886 9.62 AP1S2 AP1S1 AP1M2 AP1M1
3 vesicle-mediated transport GO:0016192 9.55 SYT6 AP1S2 AP1S1 AP1M2 AP1M1
4 antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0019886 9.26 AP1S2 AP1S1 AP1M2 AP1M1
5 regulation of defense response to virus by virus GO:0050690 8.92 AP1S2 AP1S1 AP1M2 AP1M1

Molecular functions related to Pettigrew Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 clathrin adaptor activity GO:0035615 8.62 AP1M2 AP1M1

Sources for Pettigrew 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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