MCID: PTT014
MIFTS: 52

Pitt-Hopkins Syndrome malady

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

Aliases & Classifications for Pitt-Hopkins Syndrome

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Aliases & Descriptions for Pitt-Hopkins Syndrome:

Name: Pitt-Hopkins Syndrome 49 10 11 21 45 22 23 12 51 67 36 65
Pitt Hopkins Syndrome 45 22 24
Pths 23 67
Intellectual Disability, Wide Mouth, Distinctive Facial Features, and Intermittent Hyperventilation Followed by Apnea 45
Mental Retardation Syndromal with Intermittent Hyperventilation 67
 
Encephalopathy Severe Epileptic with Autonomic Dysfunction 67
Pallister-Hall Syndrome 65
Mesh; D006985 67
Mesh; D008607 67
Phs 23

Characteristics:

Orphanet epidemiological data:

51
pitt-hopkins syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

61
pitt-hopkins syndrome:
Inheritance: autosomal dominant inheritance


Classifications:



External Ids:

OMIM49 610954
Disease Ontology10 DOID:0060488
ICD1027 Q87.0
MeSH36 C537403
Orphanet51 2896
ICD10 via Orphanet28 Q87.0
MESH via Orphanet37 C537403
UMLS via Orphanet66 C1970431
MedGen34 C1970431
UMLS65 C1970431

Summaries for Pitt-Hopkins Syndrome

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NIH Rare Diseases:45 Pitt-hopkins syndrome is a genetic condition characterized by intellectual disability and developmental delay, recurrent seizures (epilepsy), distinctive facial features, and breathing problems (i.e., periodic hyperventilation followed by apnea). this condition is caused by mutations in the tcf4 transcription factor gene. pitt-hopkins syndrome is inherited in an autosomal dominant pattern. most cases, however, result from a new (de novo) mutation and occur on people with no history of the condition in their family. treatment involves addressing the individual problems seen in each patient, and may include early intervention services, special education, and routine management of medicals concerns like seizures and myopia. last updated: 1/4/2016

MalaCards based summary: Pitt-Hopkins Syndrome, also known as pitt hopkins syndrome, is related to pth-related familial isolated hypoparathyroidism and familial isolated hypoparathyroidism due to impaired pth secretion, and has symptoms including wide mouth, abnormality of the teeth and abnormality of the palate. An important gene associated with Pitt-Hopkins Syndrome is TCF4 (Transcription Factor 4), and among its related pathways is CDO in myogenesis. Affiliated tissues include brain, testes and skin, and related mouse phenotypes are taste/olfaction and nervous system.

Disease Ontology:10 A syndrome characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features. It is caused by heterozygous de novo mutations in the TCF4 gene in chromosome 18q21.

UniProtKB/Swiss-Prot:67 Pitt-Hopkins syndrome: A syndrome characterized by mental retardation, wide mouth and distinctive facial features, and intermittent hyperventilation followed by apnea. Features include intellectual disability with severe speech impairment, normal growth parameters at birth, postnatal microcephaly, breathing anomalies, severe motor developmental delay, motor incoordination, ocular anomalies, constipation, seizures, typical behavior and subtle brain abnormalities.

Genetics Home Reference:23 Pitt-Hopkins syndrome is a condition characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features.

OMIM:49 The Pitt-Hopkins syndrome is characterized by mental retardation, wide mouth and distinctive facial features, and... (610954) more...

GeneReviews summary for NBK100240

Related Diseases for Pitt-Hopkins Syndrome

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Diseases in the Pitt-Hopkins Syndrome family:

Pitt-Hopkins-Like Syndrome 2 Pitt-Hopkins-Like Syndrome

Diseases related to Pitt-Hopkins Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50)    (show all 63)
idRelated DiseaseScoreTop Affiliating Genes
1pth-related familial isolated hypoparathyroidism12.3
2familial isolated hypoparathyroidism due to impaired pth secretion12.3
3pallister-hall syndrome11.5
4hyperoxaluria, primary, type iii11.5
5hyperphenylalaninemia, bh4-deficient, d11.5
6pulmonary hypertension11.0
7pitt-hopkins-like syndrome 210.9
8cortical dysplasia-focal epilepsy syndrome10.9
9lactic acidosis10.8
10lung cancer10.8
11alzheimer disease10.7
12influenza10.7
13metabolic acidosis10.7
14obesity10.7
15sarcoma10.7
16prostatitis10.7
17neuroblastoma10.7
18renal osteodystrophy10.6
19pseudohypoparathyroidism, type ib10.6
20colorectal cancer10.6
21smith-lemli-opitz syndrome10.6
22pancreatic ductal adenocarcinoma10.6
23hyperparathyroidism10.6
24neural tube defects10.6
25ischemic heart disease10.6
26dengue disease10.6
27dengue hemorrhagic fever10.6
28pulmonary tuberculosis10.6
29acute lymphocytic leukemia10.5
30islet cell tumor10.5
31leukemia10.5
32paroxysmal nocturnal hemoglobinuria10.5
33cortical blindness10.5
34hypertrophic cardiomyopathy10.5
35cholera10.5
36hyperinsulinism10.5
37neurilemmoma10.5
38syringomyelia10.5
39gastritis10.5
40pancreatitis10.5
41hemoglobinuria10.5
42neuropathy10.5
43atrophic gastritis10.5
44otitis externa10.5
45pulmonic stenosis10.5
46soft tissue sarcoma10.5
47cardiomyopathy10.5
48paresthesia10.5
49hypocalcemia, autosomal dominant10.4
50pseudohypoparathyroidism ia10.4

Graphical network of the top 20 diseases related to Pitt-Hopkins Syndrome:



Diseases related to pitt-hopkins syndrome

Symptoms for Pitt-Hopkins Syndrome

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Symptoms by clinical synopsis from OMIM:

610954

Clinical features from OMIM:

610954

Symptoms:

 51 (show all 24)
  • microcephaly
  • deepset eyes/enophthalmos
  • anteverted nares/nostrils
  • macrostomia/big mouth
  • thick lips
  • palate anomalies
  • abnormal dentition/dental position/implantation/unerupted/dental ankylosis
  • helix thickened/sculpted
  • gastroesophageal reflux/pyrosis/esophagitis/hiatal hernia/gastroparesia
  • constipation
  • ataxia/incoordination/trouble of the equilibrium
  • hypotonia
  • speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • autosomal dominant inheritance
  • failure to thrive/difficulties for feeding in infancy/growth delay
  • myopia
  • tapered fingers
  • respiratory rhythm disorder
  • apnea/sleep apnea
  • undescended/ectopic testes/cryptorchidia/unfixed testes
  • seizures/epilepsy/absences/spasms/status epilepticus
  • irregular/patchy skin hypopigmentation
  • micropenis/small penis/agenesis

HPO human phenotypes related to Pitt-Hopkins Syndrome:

(show all 58)
id Description Frequency HPO Source Accession
1 wide mouth hallmark (90%) HP:0000154
2 abnormality of the teeth hallmark (90%) HP:0000164
3 abnormality of the palate hallmark (90%) HP:0000174
4 thick lower lip vermilion hallmark (90%) HP:0000179
5 microcephaly hallmark (90%) HP:0000252
6 thickened helices hallmark (90%) HP:0000391
7 anteverted nares hallmark (90%) HP:0000463
8 deeply set eye hallmark (90%) HP:0000490
9 muscular hypotonia hallmark (90%) HP:0001252
10 constipation hallmark (90%) HP:0002019
11 neurological speech impairment hallmark (90%) HP:0002167
12 incoordination hallmark (90%) HP:0002311
13 cognitive impairment hallmark (90%) HP:0100543
14 cryptorchidism typical (50%) HP:0000028
15 myopia typical (50%) HP:0000545
16 tapered finger typical (50%) HP:0001182
17 seizures typical (50%) HP:0001250
18 apnea typical (50%) HP:0002104
19 hypopigmented skin patches occasional (7.5%) HP:0001053
20 hypoplasia of penis occasional (7.5%) HP:0008736
21 cryptorchidism HP:0000028
22 micropenis HP:0000054
23 open mouth HP:0000194
24 microcephaly HP:0000252
25 coarse facial features HP:0000280
26 full cheeks HP:0000293
27 short philtrum HP:0000322
28 narrow forehead HP:0000341
29 cupped ear HP:0000378
30 wide nasal bridge HP:0000431
31 short neck HP:0000470
32 astigmatism HP:0000483
33 strabismus HP:0000486
34 deeply set eye HP:0000490
35 myopia HP:0000545
36 upslanted palpebral fissure HP:0000582
37 widely spaced teeth HP:0000687
38 aggressive behavior HP:0000718
39 single transverse palmar crease HP:0000954
40 tapered finger HP:0001182
41 clubbing HP:0001217
42 seizures HP:0001250
43 muscular hypotonia HP:0001252
44 motor delay HP:0001270
45 encephalopathy HP:0001298
46 absent speech HP:0001344
47 pes planus HP:0001763
48 narrow foot HP:0001786
49 constipation HP:0002019
50 gastroesophageal reflux HP:0002020
51 gait ataxia HP:0002066
52 hypoplasia of the corpus callosum HP:0002079
53 incoordination HP:0002311
54 dysautonomia HP:0002459
55 intermittent hyperventilation HP:0004879
56 intellectual disability, progressive HP:0006887
57 intellectual disability, severe HP:0010864
58 clinodactyly HP:0030084

Drugs & Therapeutics for Pitt-Hopkins Syndrome

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Interventional clinical trials:

Search ClinicalTrials, NIH Clinical Center for Pitt-Hopkins Syndrome


Cochrane evidence based reviews: pitt-hopkins syndrome

Genetic Tests for Pitt-Hopkins Syndrome

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Genetic tests related to Pitt-Hopkins Syndrome:

id Genetic test Affiliating Genes
1 Pitt-Hopkins Syndrome22 TCF4

Anatomical Context for Pitt-Hopkins Syndrome

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MalaCards organs/tissues related to Pitt-Hopkins Syndrome:

33
Brain, Testes, Skin, Eye, Lung, Endothelial, Uterus

Animal Models for Pitt-Hopkins Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Pitt-Hopkins Syndrome:

38
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053949.0ASCL1, CDKL5, CNTNAP2
2MP:00036316.9ASCL1, CDKL5, CNTNAP2, MEF2C, NRXN1, SLC9A6
3MP:00053866.4ASCL1, CDKL5, CHD6, CNTNAP2, MEF2C, NRXN1

Publications for Pitt-Hopkins Syndrome

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Articles related to Pitt-Hopkins Syndrome:

(show all 35)
idTitleAuthorsYear
1
An Unusual Cause of a High Carbonhydrate Antigen 19-9 Level in an Elderly Individual: Polycystic Liver Disease. (26189862)
2015
2
Insulinlike Growth Factor-1 and Its Binding Protein-3 Polymorphisms Predict Circulating IGF-1 Level and Appendicular Skeletal Muscle Mass in Chinese Elderly. (25548030)
2015
3
Aripiprazole: A Review of Its Use in the Treatment of Manic Episodes in Adolescents with Bipolar I Disorder. (24399490)
2014
4
Immunohistochemical loss of BRCA1 protein in uterine serous carcinoma. (24681740)
2014
5
Thrombocytopenia: an early marker of late mortality in type B aortic dissection. (23604315)
2013
6
Serum lemur tyrosine kinase 3 expression in colorectal cancer patients predicts cancer progression and prognosis. (24174317)
2013
7
Risk factors for variant Creutzfeldt-Jakob disease in dental practice: a case-control study. (23222357)
2012
8
Stewart-Treves syndrome arising in patients with lymphaticovenular anastomosis for chronic lymphedema of the leg. (22522788)
2012
9
MAPK signaling pathways regulate IL-8 mRNA stability and IL-8 protein expression in cystic fibrosis lung epithelial cell lines. (20952496)
2011
10
HLA-Cw*1202-B*5201-DRB1*1502 haplotype increases risk for ulcerative colitis but reduces risk for Crohn's disease. (21699788)
2011
11
Gardner syndrome complicated with hydronephrosis. A case report. (22470715)
2010
12
Heterozygous glucokinase mutations and birth weight in Spanish children. (20536962)
2010
13
Reliability and validity of pendulum test measures of spasticity obtained with the Polhemus tracking system from patients with chronic stroke. (19642989)
2009
14
Targeting the RET pathway in thyroid cancer. (19934298)
2009
15
Association between tortilla consumption and human urinary fumonisin B1 levels in a Mexican population. (18349288)
2008
16
Mutation of F417 but not of L418 or L420 in the lipid binding domain decreases the activity of triacylglycerol hydrolase. (16282638)
2006
17
Investigating four 'myths' surrounding dysphagia in patients with metastatic esophageal cancer. A multi-institutional study from the North Central Cancer Treatment Group. (15569365)
2004
18
Apolipoprotein E polymorphism in ischemic cerebrovascular diseases and vascular dementia patients in Taiwan. (15084782)
2004
19
The fibril-associated collagen IX provides a novel mechanism for cell adhesion to cartilaginous matrix. (15383545)
2004
20
Is the factor XIII 34Val/Leu polymorphism a protective factor for cerebrovascular disease? (12542492)
2003
21
TEL-JAK2 mediates constitutive activation of the phosphatidylinositol 3'-kinase/protein kinase B signaling pathway. (11435425)
2001
22
Chronic intestinal pseudo-obstruction. (11060471)
2000
23
Arteriosclerosis in rat aortic allografts: early changes in endothelial integrity and smooth muscle phenotype. (10919577)
2000
24
Topical clindamycin versus systemic tetracycline in the treatment of hidradenitis suppurativa. (9843011)
1998
25
Mapping of amino acid residues in the p34 subunit of human single- stranded DNA-binding protein phosphorylated by DNA-dependent protein kinase and Cdc2 kinase in vitro. (9139719)
1997
26
Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice. (7816818)
1995
27
Protein tyrosine (de-)phosphorylation in head and neck squamous cell carcinoma. (8179861)
1994
28
Differential reduction in the volume of leiomyoma and uterus during buserelin treatment. (8059616)
1994
29
In vitro reversal of heparin effect with heparinase: evaluation with whole blood prothrombin time and activated partial thromboplastin time in cardiac surgical patients. (7943773)
1994
30
Cataract development and cataract surgery in patients with juvenile rheumatoid arthritis-associated iridocyclitis. (8510892)
1993
31
Isolation of turkey rhinotracheitis virus from five-day-old turkeys. (3132782)
1988
32
The sequelae of Osgood-Schlatter's disease in adults. (3182124)
1988
33
Pharmacokinetics and therapeutic efficacy of gentamicin in an experimental pleural empyema rabbit model. (3116920)
1987
34
Immunofluorescence identification of Thermopolyspora polyspora, the causative agent of farmer's lung. (4976327)
1969
35

Variations for Pitt-Hopkins Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Pitt-Hopkins Syndrome:

67 (show all 13)
id Symbol AA change Variation ID SNP ID
1TCF4p.Arg576GlnVAR_034704
2TCF4p.Arg576TrpVAR_034705
3TCF4p.Asp535GlyVAR_058632
4TCF4p.Arg572GlyVAR_058633
5TCF4p.Ala610ValVAR_058634
6TCF4p.Gly358ValVAR_066839
7TCF4p.Arg574ProVAR_066840
8TCF4p.Arg578HisVAR_066841
9TCF4p.Arg565TrpVAR_066970
10TCF4p.Arg572GlnVAR_066971
11TCF4p.Arg574HisVAR_066972
12TCF4p.Arg578ProVAR_066973
13TCF4p.Ala583ProVAR_066974

Clinvar genetic disease variations for Pitt-Hopkins Syndrome:

5 (show all 33)
id Gene Variation Type Significance SNP ID Assembly Location
1TCF4NM_001083962.1(TCF4): c.1146+1G> Asingle nucleotide variantPathogenicrs587784458GRCh37Chr 18, 52924545: 52924545
2TCF4NM_001083962.1(TCF4): c.1498G> T (p.Gly500Ter)single nucleotide variantPathogenicrs587784459GRCh37Chr 18, 52899891: 52899891
3TCF4NM_001083962.1(TCF4): c.1741G> T (p.Val581Phe)single nucleotide variantLikely pathogenicrs587784460GRCh37Chr 18, 52896216: 52896216
4TCF4NM_001083962.1(TCF4): c.1840G> C (p.Ala614Pro)single nucleotide variantLikely pathogenicrs587784462GRCh37Chr 18, 52896117: 52896117
5TCF4NM_001083962.1(TCF4): c.415delC (p.Leu139Phefs)deletionPathogenicrs587784463GRCh37Chr 18, 53018189: 53018189
6TCF4NM_001083962.1(TCF4): c.469C> T (p.Arg157Ter)single nucleotide variantPathogenicrs587784464GRCh37Chr 18, 53018135: 53018135
7TCF4NM_001083962.1(TCF4): c.655+1G> Asingle nucleotide variantPathogenicrs587784465GRCh37Chr 18, 52946781: 52946781
8TCF4NM_001083962.1(TCF4): c.656-1G> Csingle nucleotide variantPathogenicrs587784466GRCh37Chr 18, 52942984: 52942984
9TCF4NM_001083962.1(TCF4): c.791delG (p.Ser264Thrfs)deletionPathogenicrs587784468GRCh37Chr 18, 52937193: 52937193
10TCF4NM_001083962.1(TCF4): c.990G> A (p.Ser330=)single nucleotide variantLikely pathogenicrs587784469GRCh37Chr 18, 52928697: 52928697
11TCF4NM_001083962.1(TCF4): c.991-2A> Gsingle nucleotide variantPathogenicrs587784470GRCh37Chr 18, 52927260: 52927260
12TCF4NM_001083962.1(TCF4): c.1414delG (p.Val472Phefs)deletionPathogenicrs727504174GRCh37Chr 18, 52901851: 52901851
13TCF4NM_001083962.1(TCF4): c.1357dupA (p.Thr453Asnfs)duplicationPathogenicrs786200992GRCh37Chr 18, 52901908: 52901908
14TCF4NM_001083962.1(TCF4): c.748C> T (p.Gln250Ter)single nucleotide variantPathogenicrs727504175GRCh37Chr 18, 52942891: 52942891
15TCF4NM_001083962.1(TCF4): c.655+1G> Tsingle nucleotide variantPathogenicrs587784465GRCh37Chr 18, 52946781: 52946781
16TCF4NM_001083962.1(TCF4): c.1438C> T (p.Gln480Ter)single nucleotide variantPathogenicrs727505396GRCh38Chr 18, 55234596: 55234596
17TCF4NM_001083962.1(TCF4): c.968C> T (p.Ala323Val)single nucleotide variantPathogenicrs797045003GRCh38Chr 18, 55261488: 55261488
18TCF4NM_001083962.1(TCF4): c.1069+1G> Tsingle nucleotide variantPathogenicrs797045072GRCh37Chr 18, 52927179: 52927179
19TCF4NM_001083962.1(TCF4): c.1411C> T (p.Gln471Ter)single nucleotide variantPathogenicrs797046033GRCh37Chr 18, 52901854: 52901854
20TCF4NM_001083962.1(TCF4): c.1871A> C (p.Gln624Pro)single nucleotide variantLikely pathogenicrs797046034GRCh37Chr 18, 52896086: 52896086
21TCF4NM_001083962.1(TCF4): c.1965dupC (p.Gly656Argfs)duplicationLikely pathogenic, Pathogenicrs797046035GRCh38Chr 18, 55228276: 55228276
22TCF4NM_001083962.1(TCF4): c.655+2_655+3insGTinsertionPathogenicrs797046036GRCh37Chr 18, 52946779: 52946780
23TCF4NM_003199.2(TCF4): c.978delAinsGG (p.Ala327Glyfs)indelPathogenicrs863223404GRCh37Chr 18, 52928709: 52928710
24TCF4NM_001083962.1(TCF4): c.550-2A> Gsingle nucleotide variantLikely pathogenicrs863224934GRCh38Chr 18, 55279658: 55279658
25TCF4NM_001083962.1(TCF4): c.1738C> T (p.Arg580Trp)single nucleotide variantPathogenicrs121909120GRCh37Chr 18, 52896219: 52896219
26TCF4NM_001083962.1(TCF4): c.1739G> A (p.Arg580Gln)single nucleotide variantPathogenicrs121909121GRCh37Chr 18, 52896218: 52896218
27TCF4NM_001083962.1(TCF4): c.1153C> T (p.Arg385Ter)single nucleotide variantPathogenicrs121909122GRCh37Chr 18, 52921925: 52921925
28TCF4TCF4, IVS9AS, G-C, -1single nucleotide variantPathogenic
29TCF4NM_001083962.1(TCF4): c.1733G> C (p.Arg578Pro)single nucleotide variantPathogenicrs121909123GRCh37Chr 18, 52896224: 52896224
30TCF4TCF4, 1-BP DEL, 908CdeletionPathogenic
31TCF4NM_001083962.1(TCF4): c.1086G> A (p.Trp362Ter)single nucleotide variantPathogenicrs398123560GRCh37Chr 18, 52924606: 52924606
32TCF4NM_001083962.1(TCF4): c.1733G> A (p.Arg578His)single nucleotide variantPathogenicrs121909123GRCh37Chr 18, 52896224: 52896224
33TCF4NM_001083962.1(TCF4): c.514_517delAAAG (p.Lys172Phefs)deletionPathogenicrs398123561GRCh37Chr 18, 53017622: 53017625

Expression for genes affiliated with Pitt-Hopkins Syndrome

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Search GEO for disease gene expression data for Pitt-Hopkins Syndrome.

Pathways for genes affiliated with Pitt-Hopkins Syndrome

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Pathways related to Pitt-Hopkins Syndrome according to GeneCards Suite gene sharing:

idSuper pathwaysScoreTop Affiliating Genes
1
Show member pathways
9.3MEF2C, TCF4

GO Terms for genes affiliated with Pitt-Hopkins Syndrome

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Biological processes related to Pitt-Hopkins Syndrome according to GeneCards Suite gene sharing:

(show all 8)
idNameGO IDScoreTop Affiliating Genes
1vocalization behaviorGO:007162510.0CNTNAP2, NRXN1
2adult behaviorGO:00305349.9CNTNAP2, NRXN1
3social behaviorGO:00351769.7CNTNAP2, NRXN1
4regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activityGO:20003119.6MEF2C, NRXN1
5cerebral cortex developmentGO:00219879.4ASCL1, CNTNAP2
6neuron differentiationGO:00301829.2ASCL1, MEF2C
7positive regulation of neuron differentiationGO:00456669.1ASCL1, MEF2C
8neuron migrationGO:00017648.2ASCL1, CDKL5, MEF2C

Molecular functions related to Pitt-Hopkins Syndrome according to GeneCards Suite gene sharing:

idNameGO IDScoreTop Affiliating Genes
1chromatin bindingGO:00036829.3MEF2C, TCF4

Sources for Pitt-Hopkins Syndrome

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2CDC
14ExPASy
15FDA
16FMA
24GTR
25HGMD
26HMDB
27ICD10
28ICD10 via Orphanet
29ICD9CM
30IUPHAR
31KEGG
34MedGen
36MeSH
37MESH via Orphanet
38MGI
41NCI
42NCIt
43NDF-RT
46NINDS
47Novoseek
49OMIM
50OMIM via Orphanet
54PubMed
55QIAGEN
60SNOMED-CT via Orphanet
64Tumor Gene Family of Databases
65UMLS
66UMLS via Orphanet