MCID: PTT014
MIFTS: 54

Pitt-Hopkins Syndrome malady

Genetic diseases, Rare diseases, Neuronal diseases, Mental diseases categories

Summaries for Pitt-Hopkins Syndrome

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NIH Rare Diseases:41 Pitt-hopkins syndrome is a genetic condition characterized by intellectual disability, a wide mouth, other distinctive facial features, and abnormal breathing (i.e., periodic hyperventilation followed by apnea). it is believed that the syndrome is associated with mutations in the tcf4 transcription factor gene. the majority of cases reported thus far are believed to be sporadic; therefore, most of the individuals who have pitt-hopkins syndrome do not have any family members with the condition. treatment is symptomatic. last updated: 11/26/2013

MalaCards based summary: Pitt-Hopkins Syndrome, also known as pitt hopkins syndrome, is related to leukemia and hyperparathyroidism, 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 are Regulation of Wnt-mediated beta catenin signaling and target gene transcription and Human Embryonic Stem Cell Pluripotency. The compound mononucleotide have been mentioned in the context of this disorder. Affiliated tissues include testes, eye and skin, and related mouse phenotypes are taste/olfaction and craniofacial.

Genetics Home Reference:21 Pitt-Hopkins syndrome is a condition characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features.

OMIM:45 The Pitt-Hopkins syndrome is characterized by mental retardation, wide mouth and distinctive facial features, and... (610954) more...

GeneReviews summary for pitt-hopkins

Aliases & Classifications for Pitt-Hopkins Syndrome

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Sources:
60UMLS, 45OMIM, 10diseasecard, 19GeneReviews, 41NIH Rare Diseases, 21Genetics Home Reference, 47Orphanet, 20GeneTests, 22GTR, 34MESH via Orphanet, 26ICD10 via Orphanet, 61UMLS via Orphanet
See all sources

Pitt-Hopkins Syndrome, Aliases & Descriptions:

Name: Pitt-Hopkins Syndrome 45 10 19 41 21 47 60
Pitt Hopkins Syndrome 41 20 22
Mental Retardation, Wide Mouth, Distinctive Facial Features, and Intermittent Hyperventilation Followed by Apnea 41
 
Pallister-Hall Syndrome 60
Pths 21
Phs 21


Classifications:

Malacards categories (disease lists): (See all malacards categories)
Global: Genetic diseases, Rare diseases
Anatomical: Neuronal diseases, Mental diseases


Characteristics (Orphanet epidemiological data):

47
pitt-hopkins syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal


External Ids:

OMIM45 610954
Orphanet47 2896
MESH via Orphanet34 C537403
ICD10 via Orphanet26 Q87.0
UMLS via Orphanet61 C1970431

Related Diseases for Pitt-Hopkins Syndrome

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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:

 47 (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 57)
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 autosomal dominant inheritance HP:0000006
22 cryptorchidism HP:0000028
23 micropenis HP:0000054
24 open mouth HP:0000194
25 microcephaly HP:0000252
26 coarse facial features HP:0000280
27 full cheeks HP:0000293
28 short philtrum HP:0000322
29 narrow forehead HP:0000341
30 cupped ear HP:0000378
31 wide nasal bridge HP:0000431
32 short neck HP:0000470
33 astigmatism HP:0000483
34 strabismus HP:0000486
35 deeply set eye HP:0000490
36 myopia HP:0000545
37 upslanted palpebral fissure HP:0000582
38 widely spaced teeth HP:0000687
39 aggressive behavior HP:0000718
40 single transverse palmar crease HP:0000954
41 tapered finger HP:0001182
42 clubbing HP:0001217
43 seizures HP:0001250
44 muscular hypotonia HP:0001252
45 motor delay HP:0001270
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 hyperventilation HP:0002883
55 intellectual disability, progressive HP:0006887
56 intellectual disability, severe HP:0010864
57 clinodactyly HP:0030084

Drugs & Therapeutics for Pitt-Hopkins Syndrome

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Drug clinical trials:

Search ClinicalTrials for Pitt-Hopkins Syndrome

Search NIH Clinical Center for 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 Syndrome20 22 TCF4

Anatomical Context for Pitt-Hopkins Syndrome

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MalaCards organs/tissues related to Pitt-Hopkins Syndrome:

31
Testes, Eye, Skin

Animal Models for Pitt-Hopkins Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Pitt-Hopkins Syndrome:

35
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053949.4GLI3, CNTNAP2
2MP:00053828.7TCF7L2, TCF4, GLI3
3MP:00053848.5TCF7L2, TCF4, CNTNAP2, GLI3
4MP:00053868.0CNTNAP2, NRXN1, TCF7L2, CHD6
5MP:00036317.7NRXN1, TCF7L2, TCF4, CNTNAP2, GLI3

Publications for Pitt-Hopkins Syndrome

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Articles related to Pitt-Hopkins Syndrome:

(show all 35)
idTitleAuthorsYear
1
Successful use of acetazolamide for central apnea in a child with Pitt-Hopkins syndrome. (25900839)
2015
2
Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription. (23640545)
2013
3
Somatic mosaicism in a mother of two children with Pitt-Hopkins syndrome. (22335494)
2013
4
A case of Pitt-Hopkins syndrome with absence of hyperventilation. (23248353)
2013
5
263.4A kb deletion within the TCF4 gene consistent with Pitt-Hopkins syndrome, inherited from a mosaic parent with normal phenotype. (23528641)
2013
6
Previously unreported difficult intubation in a child with Pitt-Hopkins syndrome. (24383606)
2013
7
Tissue-limited ring chromosome 18 mosaicism as a cause of Pitt-Hopkins syndrome. (22887345)
2012
8
Pitt-Hopkins syndrome in a boy with Charcot Marie Tooth disease type 1A: a rare co-occurrence of 2 genetic disorders. (22378661)
2012
9
Acetazolamide for severe apnea in Pitt-Hopkins syndrome. (22407847)
2012
10
Pitt-Hopkins syndrome-associated mutations in TCF4 lead to variable impairment of the transcription factor function ranging from hypomorphic to dominant-negative effects. (22460224)
2012
11
Clinical and polygraphic improvement of breathing abnormalities after valproate in a case of Pitt-Hopkins syndrome. (22378662)
2012
12
Functional analysis of TCF4 missense mutations that cause Pitt- Hopkins syndrome. (22777675)
2012
13
Pitt-Hopkins Syndrome. (22670138)
2012
14
Development, cognition, and behaviour in Pitt-Hopkins syndrome. (22712893)
2012
15
Proposal of a clinical score for the molecular test for Pitt-Hopkins syndrome. (22678594)
2012
16
Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome: clinical score and further delineation of the TCF4 mutational spectrum. (22045651)
2012
17
Pitt-Hopkins syndrome should be in the differential diagnosis for males presenting with an ATR-X phenotype. (22040220)
2011
18
Fetal pads as a clue to the diagnosis of Pitt-Hopkins syndrome. (21671383)
2011
19
The Pitt-Hopkins syndrome: report of 16 new patients and clinical diagnostic criteria. (21671391)
2011
20
Neurologic and ocular phenotype in Pitt-Hopkins syndrome and a zebrafish model. (21544580)
2011
21
TCF4, schizophrenia, and Pitt-Hopkins Syndrome. (20421335)
2010
22
Pitt-Hopkins syndrome: report of a case with a TCF4 gene mutation. (20205897)
2010
23
Genotype-phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations. (19938247)
2009
24
Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. (19235238)
2009
25
Hyperventilation and the Pitt-Hopkins syndrome. (18611190)
2008
26
Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome. (18627065)
2008
27
TCF4 deletions in Pitt-Hopkins Syndrome. (18781613)
2008
28
Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic description of 16 novel patients. (18728071)
2008
29
Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4. (17478476)
2007
30
Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome). (17436255)
2007
31
Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction. (17436254)
2007
32
Pitt-Hopkins syndrome in two patients and further definition of the phenotype. (16531728)
2006
33
Possible case of Pitt-Hopkins syndrome in sibs. (11568923)
2001
34
Mental retardation, &quot;coarse&quot; face, and hyperbreathing: confirmation of the Pitt-Hopkins syndrome. (9475596)
1998
35
Pitt-Hopkins Syndrome (22934316)
1993

Variations for Pitt-Hopkins Syndrome

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

62 (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:

6 (show all 35)
id Gene Variation Type Significance SNP ID Assembly Location
1GLI3NM_000168.5(GLI3): c.2023delG (p.Glu675Serfs)deletionPathogenicrs116840744GRCh37Chr 7, 42012016: 42012016
2GLI3NM_000168.5(GLI3): c.2012delG (p.Gly671Glufs)deletionPathogenicrs116840743GRCh37Chr 7, 42012027: 42012027
3GLI3NM_000168.5(GLI3): c.3439G> T (p.Glu1147Ter)single nucleotide variantPathogenicrs116840768GRCh37Chr 7, 42005232: 42005232
4GLI3NM_000168.5: c.2770_2771insNC_012920.1: g.12243..12314insertionPathogenicGRCh37Chr 7, 42005900: 42005901
5GLI3NM_000168.5(GLI3): c.1998_2001delCCGA (p.Pro668Leufs)deletionPathogenicrs116840742GRCh37Chr 7, 42012038: 42012041
6GLI3NM_000168.5(GLI3): c.2032delG (p.Asp678Thrfs)deletionPathogenicrs116840745GRCh37Chr 7, 42012007: 42012007
7GLI3NM_000168.5(GLI3): c.2058_2059delGGinsAT (p.Glu687Ter)indelPathogenicrs116840746GRCh37Chr 7, 42011980: 42011981
8GLI3NM_000168.5(GLI3): c.2062G> T (p.Glu688Ter)single nucleotide variantPathogenicrs116840747GRCh37Chr 7, 42011977: 42011977
9GLI3NM_000168.5(GLI3): c.2110C> T (p.Gln704Ter)single nucleotide variantPathogenicrs116840748GRCh37Chr 7, 42007515: 42007515
10GLI3NM_000168.5(GLI3): c.2139delC (p.Cys713Terfs)deletionPathogenicrs116840749GRCh37Chr 7, 42007486: 42007486
11GLI3NM_000168.5(GLI3): c.2146C> T (p.Gln716Ter)single nucleotide variantPathogenicrs116840750GRCh37Chr 7, 42007479: 42007479
12GLI3NM_000168.5(GLI3): c.2149C> T (p.Gln717Ter)single nucleotide variantPathogenicrs116840751GRCh37Chr 7, 42007476: 42007476
13GLI3NM_000168.5(GLI3): c.2157delC (p.Ile720Serfs)deletionPathogenicrs116840752GRCh37Chr 7, 42007468: 42007468
14GLI3NM_000168.5(GLI3): c.2172dupC (p.Asn725Glnfs)duplicationPathogenicrs116840753GRCh37Chr 7, 42007452: 42007453
15GLI3NM_000168.5(GLI3): c.2197_2198delAC (p.Thr733Argfs)deletionPathogenicrs116840755GRCh37Chr 7, 42007427: 42007428
16GLI3NM_000168.5(GLI3): c.2346_2356delGCTAAAACAAG (p.Arg782Serfs)deletionPathogenicrs116840756GRCh37Chr 7, 42007269: 42007279
17GLI3NM_000168.5(GLI3): c.2351_2355delAACAA (p.Lys784Serfs)deletionPathogenicrs116840757GRCh37Chr 7, 42007270: 42007274
18GLI3NM_000168.5(GLI3): c.2431+1G> Asingle nucleotide variantPathogenicrs116840758GRCh37Chr 7, 42007193: 42007193
19GLI3NM_000168.5(GLI3): c.2483delC (p.Pro828Argfs)deletionPathogenicrs116840759GRCh37Chr 7, 42006188: 42006188
20GLI3NM_000168.5(GLI3): c.2567C> A (p.Ser856Ter)single nucleotide variantPathogenicrs116840760GRCh37Chr 7, 42006104: 42006104
21GLI3NM_000168.5(GLI3): c.2620delC (p.Arg874Alafs)deletionPathogenicrs116840761GRCh37Chr 7, 42006051: 42006051
22GLI3NM_000168.5(GLI3): c.2628delC (p.Ser877Alafs)deletionPathogenicrs116840762GRCh37Chr 7, 42006043: 42006043
23GLI3NM_000168.5(GLI3): c.2799C> G (p.Tyr933Ter)single nucleotide variantPathogenicrs116840763GRCh37Chr 7, 42005872: 42005872
24GLI3NM_000168.5(GLI3): c.2935delT (p.Cys979Alafs)deletionPathogenicrs116840764GRCh37Chr 7, 42005736: 42005736
25GLI3NM_000168.5(GLI3): c.3004delG (p.Val1002Terfs)deletionPathogenicrs116840765GRCh37Chr 7, 42005667: 42005667
26GLI3NM_000168.5(GLI3): c.3324C> G (p.Tyr1108Ter)single nucleotide variantPathogenicrs116840766GRCh37Chr 7, 42005347: 42005347
27GLI3NM_000168.5(GLI3): c.3386_3387delTT (p.Phe1129Terfs)deletionPathogenicrs281864935GRCh37Chr 7, 42005284: 42005285
28GLI3NM_000168.5(GLI3): c.3456G> T (p.Glu1152Asp)single nucleotide variantPathogenicrs116840769GRCh37Chr 7, 42005215: 42005215
29GLI3NM_000168.5(GLI3): c.3481C> T (p.Gln1161Ter)single nucleotide variantPathogenicrs116840770GRCh37Chr 7, 42005190: 42005190
30TCF4NM_001083962.1(TCF4): c.1738C> T (p.Arg580Trp)single nucleotide variantPathogenicrs121909120GRCh37Chr 18, 52896219: 52896219
31TCF4NM_001083962.1(TCF4): c.1739G> A (p.Arg580Gln)single nucleotide variantPathogenicrs121909121GRCh37Chr 18, 52896218: 52896218
32TCF4NM_001083962.1(TCF4): c.1153C> T (p.Arg385Ter)single nucleotide variantPathogenicrs121909122GRCh37Chr 18, 52921925: 52921925
33TCF4TCF4, IVS9AS, G-C, -1single nucleotide variantPathogenic
34TCF4NM_001083962.1(TCF4): c.1733G> C (p.Arg578Pro)single nucleotide variantPathogenicrs121909123GRCh37Chr 18, 52896224: 52896224
35TCF4TCF4, 1-BP DEL, 908CdeletionPathogenic

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 pathways (with members indented)ScoreTop Affiliating Genes
19.4TCF4, TCF7L2
2
Show member pathways
9.4TCF4, TCF7L2
3
Show member pathways
9.4GLI3, TCF7L2
49.1NRXN1, CNTNAP2

Compounds for genes affiliated with Pitt-Hopkins Syndrome

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Sources:
43Novoseek
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Compounds related to Pitt-Hopkins Syndrome according to GeneCards Suite gene sharing:

idCompoundScoreTop Affiliating Genes
1mononucleotide439.4TCF4, TCF7L2

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 9)
idNameGO IDScoreTop Affiliating Genes
1embryonic digestive tract morphogenesisGO:00485579.6GLI3, TCF7L2
2odontogenesis of dentin-containing toothGO:00424759.4GLI3, TCF7L2
3vocalization behaviorGO:00716259.3NRXN1, CNTNAP2
4brain developmentGO:00074209.3CNTNAP2, TCF7L2
5negative regulation of canonical Wnt signaling pathwayGO:00900909.3GLI3, TCF7L2
6adult behaviorGO:00305349.3NRXN1, CNTNAP2
7social behaviorGO:00351769.2NRXN1, CNTNAP2
8learningGO:00076129.2CNTNAP2, NRXN1
9positive regulation of transcription from RNA polymerase II promoterGO:00459448.7TCF7L2, TCF4, GLI3

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

idNameGO IDScoreTop Affiliating Genes
1beta-catenin bindingGO:00080139.1GLI3, TCF7L2
2RNA polymerase II core promoter proximal region sequence-specific DNA bindingGO:00009789.0GLI3, TCF4, TCF7L2
3sequence-specific DNA binding transcription factor activityGO:00037009.0GLI3, TCF4, TCF7L2
4chromatin bindingGO:00036828.8CHD6, TCF7L2, GLI3

Products for genes affiliated with Pitt-Hopkins Syndrome

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Sources for Pitt-Hopkins Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
33MeSH
34MESH via Orphanet
35MGI
38NCIt
39NDF-RT
42NINDS
43Novoseek
45OMIM
46OMIM via Orphanet
50PubMed
51QIAGEN
56SNOMED-CT via Orphanet
60UMLS
61UMLS via Orphanet