PHS
MCID: PTT014
MIFTS: 59

Pitt-Hopkins Syndrome (PHS) malady

Genetic diseases, Rare diseases, Neuronal diseases, Mental diseases categories
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Summaries for Pitt-Hopkins Syndrome

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43NIH Rare Diseases, 21Genetics Home Reference, 47OMIM, 19GeneReviews, 33MalaCards
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NIH Rare Diseases:43 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: Pitt-Hopkins Syndrome, also known as pitt hopkins syndrome, is related to leukemia and hyperparathyroidism, and has symptoms including respiratory rhythm disorder, undescended/ectopic testes/cryptorchidia/unfixed testes and myopia. An important gene associated with Pitt-Hopkins Syndrome is TCF4 (transcription factor 4), and among its related pathways are WNT Signaling and Wnt Signaling Pathway. The compounds glycogen and mononucleotide have been mentioned in the context of this disorder. Affiliated tissues include testes, eye and skin, and related mouse phenotypes are nervous system and behavior/neurological.

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

Description from OMIM:47 610954

GeneReviews summary for pitt-hopkins

Aliases & Classifications for Pitt-Hopkins Syndrome

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Sources:
19GeneReviews, 43NIH Rare Diseases, 20GeneTests, 22GTR, 21Genetics Home Reference, 47OMIM, 49Orphanet, 62UMLS, 26ICD10 via Orphanet, 36MESH via Orphanet, 63UMLS via Orphanet
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Classifications:

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


Characteristics (Orphanet epidemiological data):

49
pitt-hopkins syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000; Age of onset: Neonatal/infancy


Aliases & Descriptions:

pitt-hopkins syndrome 19 43 21 47 49 62
pitt hopkins syndrome 43 20 22
mental retardation, wide mouth, distinctive facial features, and intermittent hyperventilation followed by apnea 43
deficiency of phosphorylase kinase 62
glycogen storage disease, type ix 62
pallister-hall syndrome 62
pths 21
phs 21


External Ids:

ICD10 via Orphanet26 Q87.0
OMIM47 610954
MESH via Orphanet36 C537403
UMLS via Orphanet63 C1970431

Related Diseases for Pitt-Hopkins Syndrome

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17GeneCards, 18GeneDecks
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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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47OMIM, 49Orphanet
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Symptoms by clinical synopsis from OMIM:

610954

Clinical features from OMIM:

610954

Symptoms:

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

Drugs & Therapeutics for Pitt-Hopkins Syndrome

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Sources:
42NIH Clinical Center, 6ClinicalTrials
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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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20GeneTests, 22GTR
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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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33MalaCards
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MalaCards organs/tissues related to Pitt-Hopkins Syndrome:

33
Testes, Eye, Skin

Animal Models for Pitt-Hopkins Syndrome or affiliated genes

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37MGI
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MGI Mouse Phenotypes related to Pitt-Hopkins Syndrome:

37
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00036318.1NRXN1, CNTNAP2, TCF4, TCF7L2
2MP:00053867.7NRXN1, CNTNAP2, TCF7L2, CHD6

Publications for Pitt-Hopkins Syndrome

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52PubMed
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Articles related to Pitt-Hopkins Syndrome:

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

Variations for Pitt-Hopkins Syndrome

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Sources:
64UniProtKB/Swiss-Prot, 1 National Center for Biotechnology Information (Clinvar)
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UniProtKB/Swiss-Prot genetic disease variations for Pitt-Hopkins Syndrome:

64 (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:

1 (show all 35)
id Gene Name 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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2BioGPS, 15Gene Expression Omnibus DataSets
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Expression patterns in normal tissues for genes affiliated with Pitt-Hopkins Syndrome

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

Pathways for genes affiliated with Pitt-Hopkins Syndrome

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Sources:
50PathCards, 53QIAGEN, 38NCBI BioSystems Database, 54R&D Systems, 30KEGG
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Pathways related to Pitt-Hopkins Syndrome according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
19.4TCF4, TCF7L2
2
Show member pathways
Wnt Signaling Pathway NetPath38
9.4TCF4, TCF7L2
3
Show member pathways
9.4TCF7L2, TCF4
49.4TCF4, TCF7L2
59.1NRXN1, CNTNAP2

Compounds for genes affiliated with Pitt-Hopkins Syndrome

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45Novoseek, 24HMDB
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Compounds related to Pitt-Hopkins Syndrome according to GeneCards/GeneDecks:

idCompoundScoreTop Affiliating Genes
1glycogen45 2410.4TCF4, TCF7L2
2mononucleotide459.1TCF4, TCF7L2

GO Terms for genes affiliated with Pitt-Hopkins Syndrome

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16Gene Ontology
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Cellular components related to Pitt-Hopkins Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1transcription factor complexGO:0056679.4TCF4, TCF7L2

Biological processes related to Pitt-Hopkins Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1brain developmentGO:0074209.3CNTNAP2, TCF7L2
2vocalization behaviorGO:0716259.2NRXN1, CNTNAP2
3adult behaviorGO:0305349.1NRXN1, CNTNAP2
4social behaviorGO:0351769.0CNTNAP2, NRXN1
5learningGO:0076128.8NRXN1, CNTNAP2

Molecular functions related to Pitt-Hopkins Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1chromatin bindingGO:0036829.3TCF7L2, CHD6
2RNA polymerase II core promoter proximal region sequence-specific DNA bindingGO:0009789.1TCF4, TCF7L2

Products for genes affiliated with Pitt-Hopkins Syndrome

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Sources for Pitt-Hopkins Syndrome

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4CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
29IUPHAR
30KEGG
35MeSH
36MESH via Orphanet
37MGI
40NCIt
41NDF-RT
44NINDS
45Novoseek
47OMIM
48OMIM via Orphanet
52PubMed
53QIAGEN
59SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet