PTHS
MCID: PTT014
MIFTS: 47

Pitt-Hopkins Syndrome (PTHS) 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 52 11 23 48 24 25 54 70 12 39 13 68
Pitt Hopkins Syndrome 48 24 27
Pths 25 70
Intellectual Disability, Wide Mouth, Distinctive Facial Features, and Intermittent Hyperventilation Followed by Apnea 48
Mental Retardation Syndromal with Intermittent Hyperventilation 70
 
Encephalopathy Severe Epileptic with Autonomic Dysfunction 70
Mesh; D006985 70
Mesh; D008607 70
Phs 25

Characteristics:

Orphanet epidemiological data:

54
pitt-hopkins syndrome:
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal

HPO:

64
pitt-hopkins syndrome:
Inheritance: autosomal dominant inheritance

Classifications:



External Ids:

OMIM52 610954
Disease Ontology11 DOID:0060488
MeSH39 C537403
Orphanet54 ORPHA2896
SNOMED-CT62 702344008
UMLS via Orphanet69 C1970431
ICD10 via Orphanet31 Q87.0
MESH via Orphanet40 C537403
MedGen37 C1970431

Summaries for Pitt-Hopkins Syndrome

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NIH Rare Diseases:48 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 pseudohypoparathyroidism, type ib, and has symptoms including constipation, constipation and seizures. An important gene associated with Pitt-Hopkins Syndrome is TCF4 (Transcription Factor 4), and among its related pathways is Cell adhesion molecules (CAMs). Affiliated tissues include brain, eye and testes, and related mouse phenotypes are behavior/neurological and nervous system.

Disease Ontology:11 A syndrome characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features. It has material basis in heterozygous de novo mutations in the TCF4 gene in chromosome 18q21.

Genetics Home Reference:25 Pitt-Hopkins syndrome is a condition characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures (epilepsy), and distinctive facial features.

OMIM:52 The Pitt-Hopkins syndrome is characterized by mental retardation, wide mouth and distinctive facial features, and... (610954) more...

UniProtKB/Swiss-Prot:70 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.

GeneReviews 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 81)
idRelated DiseaseScoreTop Affiliating Genes
1pth-related familial isolated hypoparathyroidism11.8
2pseudohypoparathyroidism, type ib11.4
3hypoparathyroidism, familial isolated11.4
4pulmonary hypertension11.4
5pitt-hopkins-like syndrome 211.3
6cortical dysplasia-focal epilepsy syndrome11.3
7hyperparathyroidism11.2
8hypoparathyroidism11.2
9lactic acidosis11.2
10pseudohypoparathyroidism11.1
11renal osteodystrophy11.1
12pallister-hall syndrome11.0
13hyperoxaluria, primary, type iii11.0
14metabolic acidosis11.0
15h. pylori infection11.0
16hyperphenylalaninemia, bh4-deficient, d10.9
17hypocalcemia, autosomal dominant10.9
18hypomagnesemia 1, intestinal10.9
19pseudohypoparathyroidism ia10.9
20acid sphingomyelinase deficiency10.8
21hyperparathyroidism, familial primary10.8
22pseudohypoparathyroidism ic10.8
23pseudohypoparathyroidism, type ii10.8
24smith-lemli-opitz syndrome10.7
25gitelman syndrome10.7
26leukemia, chronic myeloid, somatic10.7
27bartter disease10.7
28urinary system disease10.7
29hyperuricemia10.7
30renal tubular acidosis, distal10.7
31proximal renal tubular acidosis10.7
32hypoparathyroidism-retardation-dysmorphism syndrome10.7
33hypocalciuric hypercalcemia, type i10.7
34pseudopseudohypoparathyroidism10.7
35hypophosphatemic rickets, x-linked dominant10.7
36metaphyseal chondrodysplasia, murk jansen type10.7
37leukemia10.3
38lung cancer10.2
39alzheimer disease10.2
40intellectual disability10.2
41osteoporosis10.2
42gastroesophageal reflux10.1
43plasma cell leukemia10.0CNTNAP2, NRXN1
44esophagitis10.0
45lymphoblastic leukemia10.0
46myeloid leukemia10.0
47schizophrenia10.0
48charcot-marie-tooth disease, type 1a10.0
49charcot-marie-tooth disease10.0
50non-syndromic intellectual disability10.0

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



Diseases related to pitt-hopkins syndrome

Symptoms & Phenotypes for Pitt-Hopkins Syndrome

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Symptoms by clinical synopsis from OMIM:

610954

Clinical features from OMIM:

610954

Human phenotypes related to Pitt-Hopkins Syndrome:

 64 (show all 38)
id Description HPO Frequency HPO Source Accession
1 cryptorchidism64 HP:0000028
2 micropenis64 HP:0000054
3 open mouth64 HP:0000194
4 microcephaly64 HP:0000252
5 coarse facial features64 HP:0000280
6 full cheeks64 HP:0000293
7 short philtrum64 HP:0000322
8 narrow forehead64 HP:0000341
9 cupped ear64 HP:0000378
10 wide nasal bridge64 HP:0000431
11 short neck64 HP:0000470
12 astigmatism64 HP:0000483
13 strabismus64 HP:0000486
14 deeply set eye64 HP:0000490
15 myopia64 HP:0000545
16 upslanted palpebral fissure64 HP:0000582
17 widely spaced teeth64 HP:0000687
18 aggressive behavior64 HP:0000718
19 single transverse palmar crease64 HP:0000954
20 tapered finger64 HP:0001182
21 clubbing64 HP:0001217
22 seizures64 HP:0001250
23 muscular hypotonia64 HP:0001252
24 motor delay64 HP:0001270
25 encephalopathy64 HP:0001298
26 absent speech64 HP:0001344
27 pes planus64 HP:0001763
28 narrow foot64 HP:0001786
29 constipation64 HP:0002019
30 gastroesophageal reflux64 HP:0002020
31 gait ataxia64 HP:0002066
32 hypoplasia of the corpus callosum64 HP:0002079
33 incoordination64 HP:0002311
34 dysautonomia64 HP:0002459
35 intermittent hyperventilation64 HP:0004879
36 intellectual disability, progressive64 HP:0006887
37 intellectual disability, severe64 HP:0010864
38 clinodactyly64 HP:0030084

UMLS symptoms related to Pitt-Hopkins Syndrome:


constipation, seizures, nasal flaring, abnormal coordination

MGI Mouse Phenotypes related to Pitt-Hopkins Syndrome according to GeneCards Suite gene sharing:

41
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053868.4CDKL5, CHD6, CNTNAP2, NRXN1, SLC9A6
2MP:00036317.3CDKL5, CNTNAP2, LARP7, NRXN1, SLC9A6, TCF4

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 Syndrome27 24 TCF4

Anatomical Context for Pitt-Hopkins Syndrome

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MalaCards organs/tissues related to Pitt-Hopkins Syndrome:

36
Brain, Eye, Testes

Publications for Pitt-Hopkins Syndrome

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Articles related to Pitt-Hopkins Syndrome:

(show all 45)
idTitleAuthorsYear
1
An adapted walking intervention for a child with Pitt Hopkins syndrome(). (28125296)
2017
2
Osteopathic Manipulative Treatment Limits Chronic Constipation in a Child with Pitt-Hopkins Syndrome. (28251008)
2017
3
A case of Pitt-Hopkins syndrome presented with Angelman-like syndromic phenotypes. (27864810)
2016
4
Phenotype and natural history in 101 individuals with Pitt-Hopkins syndrome through an internet questionnaire system. (27072915)
2016
5
Neurodevelopmental models of transcription factor 4 deficiency converge on a common ion channel as a potential therapeutic target for Pitt Hopkins syndrome. (28032012)
2016
6
Partial deletion of TCF4 in three generation family with non-syndromic intellectual disability, without features of Pitt-Hopkins syndrome. (27132474)
2016
7
Introducing Pitt-Hopkins syndrome-associated mutations of TCF4 to Drosophila daughterless. (26621827)
2015
8
Pitt-Hopkins Syndrome and Differential Diagnosis: A Molecular and Clinical Challenge. (27617128)
2015
9
Successful use of acetazolamide for central apnea in a child with Pitt-Hopkins syndrome. (25900839)
2015
10
Pitt-Hopkins syndrome: Mental retardation, psychomotor and developmental delays with facial dysmorphism. (27625870)
2014
11
A case of Pitt-Hopkins syndrome with absence of hyperventilation. (23248353)
2013
12
Pitt-Hopkins Syndrome: intellectual disability due to loss of TCF4-regulated gene transcription. (23640545)
2013
13
Somatic mosaicism in a mother of two children with Pitt-Hopkins syndrome. (22335494)
2013
14
263.4A kb deletion within the TCF4 gene consistent with Pitt-Hopkins syndrome, inherited from a mosaic parent with normal phenotype. (23528641)
2013
15
Previously unreported difficult intubation in a child with Pitt-Hopkins syndrome. (24383606)
2013
16
Pitt-Hopkins Syndrome. (22670138)
2012
17
Functional analysis of TCF4 missense mutations that cause Pitt- Hopkins syndrome. (22777675)
2012
18
Acetazolamide for severe apnea in Pitt-Hopkins syndrome. (22407847)
2012
19
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
20
Development, cognition, and behaviour in Pitt-Hopkins syndrome. (22712893)
2012
21
Pitt-Hopkins syndrome in a boy with Charcot Marie Tooth disease type 1A: a rare co-occurrence of 2 genetic disorders. (22378661)
2012
22
Proposal of a clinical score for the molecular test for Pitt-Hopkins syndrome. (22678594)
2012
23
Clinical and polygraphic improvement of breathing abnormalities after valproate in a case of Pitt-Hopkins syndrome. (22378662)
2012
24
Tissue-limited ring chromosome 18 mosaicism as a cause of Pitt-Hopkins syndrome. (22887345)
2012
25
Pitt-Hopkins Syndrome (28520343)
2012
26
Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome: clinical score and further delineation of the TCF4 mutational spectrum. (22045651)
2012
27
The Pitt-Hopkins syndrome: report of 16 new patients and clinical diagnostic criteria. (21671391)
2011
28
Pitt-Hopkins syndrome should be in the differential diagnosis for males presenting with an ATR-X phenotype. (22040220)
2011
29
Fetal pads as a clue to the diagnosis of Pitt-Hopkins syndrome. (21671383)
2011
30
Neurologic and ocular phenotype in Pitt-Hopkins syndrome and a zebrafish model. (21544580)
2011
31
TCF4, schizophrenia, and Pitt-Hopkins Syndrome. (20421335)
2010
32
Pitt-Hopkins syndrome: report of a case with a TCF4 gene mutation. (20205897)
2010
33
Genotype-phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations. (19938247)
2009
34
Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. (19235238)
2009
35
Hyperventilation and the Pitt-Hopkins syndrome. (18611190)
2008
36
TCF4 deletions in Pitt-Hopkins Syndrome. (18781613)
2008
37
Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic description of 16 novel patients. (18728071)
2008
38
Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome. (18627065)
2008
39
Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome). (17436255)
2007
40
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
41
Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4. (17478476)
2007
42
Pitt-Hopkins syndrome in two patients and further definition of the phenotype. (16531728)
2006
43
Possible case of Pitt-Hopkins syndrome in sibs. (11568923)
2001
44
Mental retardation, "coarse" face, and hyperbreathing: confirmation of the Pitt-Hopkins syndrome. (9475596)
1998
45
Pitt-Hopkins Syndrome (22934316)
1993

Variations for Pitt-Hopkins Syndrome

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

70 (show all 13)
id Symbol AA change Variation ID SNP ID
1TCF4p.Arg576GlnVAR_034704rs121909121
2TCF4p.Arg576TrpVAR_034705rs121909120
3TCF4p.Asp535GlyVAR_058632
4TCF4p.Arg572GlyVAR_058633
5TCF4p.Ala610ValVAR_058634
6TCF4p.Gly358ValVAR_066839
7TCF4p.Arg574ProVAR_066840rs121909123
8TCF4p.Arg578HisVAR_066841
9TCF4p.Arg565TrpVAR_066970
10TCF4p.Arg572GlnVAR_066971
11TCF4p.Arg574HisVAR_066972rs121909123
12TCF4p.Arg578ProVAR_066973
13TCF4p.Ala583ProVAR_066974

Clinvar genetic disease variations for Pitt-Hopkins Syndrome:

5 (show all 34)
id Gene Variation Type Significance SNP ID Assembly Location
1TCF4NM_ 001083962.1(TCF4): c.1146+1G> ASNVPathogenicrs587784458GRCh37Chr 18, 52924545: 52924545
2TCF4NM_ 001083962.1(TCF4): c.1498G> T (p.Gly500Ter)SNVPathogenicrs587784459GRCh37Chr 18, 52899891: 52899891
3TCF4NM_ 001083962.1(TCF4): c.1741G> T (p.Val581Phe)SNVLikely pathogenicrs587784460GRCh38Chr 18, 55228985: 55228985
4TCF4NM_ 001083962.1(TCF4): c.1840G> C (p.Ala614Pro)SNVLikely pathogenicrs587784462GRCh38Chr 18, 55228886: 55228886
5TCF4NM_ 001083962.1(TCF4): c.415delC (p.Leu139Phefs)deletionPathogenicrs587784463GRCh38Chr 18, 55350958: 55350958
6TCF4NM_ 001083962.1(TCF4): c.469C> T (p.Arg157Ter)SNVPathogenicrs587784464GRCh38Chr 18, 55350904: 55350904
7TCF4NM_ 001083962.1(TCF4): c.655+1G> ASNVPathogenicrs587784465GRCh38Chr 18, 55279550: 55279550
8TCF4NM_ 001083962.1(TCF4): c.656-1G> CSNVPathogenicrs587784466GRCh38Chr 18, 55275753: 55275753
9TCF4NM_ 001083962.1(TCF4): c.791delG (p.Ser264Thrfs)deletionPathogenicrs587784468GRCh37Chr 18, 52937193: 52937193
10TCF4NM_ 001083962.1(TCF4): c.990G> A (p.Ser330=)SNVLikely pathogenicrs587784469GRCh37Chr 18, 52928697: 52928697
11TCF4NM_ 001083962.1(TCF4): c.991-2A> GSNVPathogenicrs587784470GRCh37Chr 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)SNVPathogenicrs727504175GRCh37Chr 18, 52942891: 52942891
15TCF4NM_ 001083962.1(TCF4): c.655+1G> TSNVPathogenicrs587784465GRCh37Chr 18, 52946781: 52946781
16TCF4NM_ 001083962.1(TCF4): c.1438C> T (p.Gln480Ter)SNVPathogenicrs727505396GRCh38Chr 18, 55234596: 55234596
17TCF4NM_ 001083962.1(TCF4): c.968C> T (p.Ala323Val)SNVPathogenicrs797045003GRCh38Chr 18, 55261488: 55261488
18TCF4NM_ 001083962.1(TCF4): c.1069+1G> TSNVPathogenicrs797045072GRCh37Chr 18, 52927179: 52927179
19TCF4NM_ 001083962.1(TCF4): c.1411C> T (p.Gln471Ter)SNVPathogenicrs797046033GRCh37Chr 18, 52901854: 52901854
20TCF4NM_ 001083962.1(TCF4): c.1871A> C (p.Gln624Pro)SNVLikely pathogenicrs797046034GRCh37Chr 18, 52896086: 52896086
21TCF4NM_ 001083962.1(TCF4): c.1965dupC (p.Gly656Argfs)duplicationPathogenic/ Likely pathogenicrs797046035GRCh37Chr 18, 52895507: 52895507
22TCF4NM_ 001083962.1(TCF4): c.655+2_ 655+3insGTinsertionPathogenicrs797046036GRCh37Chr 18, 52946779: 52946780
23TCF4NM_ 003199.2(TCF4): c.978delAinsGG (p.Ala327Glyfs)indelPathogenicrs863223404GRCh37Chr 18, 52928709: 52928709
24TCF4NM_ 001083962.1(TCF4): c.550-2A> GSNVLikely pathogenicrs863224934GRCh38Chr 18, 55279658: 55279658
25TCF4NM_ 001243234.1(TCF4): c.656dupT (p.Leu219Phefs)duplicationLikely pathogenicrs1057519592GRCh37Chr 18, 52924556: 52924556
26TCF4NM_ 001083962.1(TCF4): c.1738C> T (p.Arg580Trp)SNVPathogenic/ Likely pathogenicrs121909120GRCh37Chr 18, 52896219: 52896219
27TCF4NM_ 001083962.1(TCF4): c.1739G> A (p.Arg580Gln)SNVPathogenicrs121909121GRCh37Chr 18, 52896218: 52896218
28TCF4NM_ 001083962.1(TCF4): c.1153C> T (p.Arg385Ter)SNVPathogenicrs121909122GRCh37Chr 18, 52921925: 52921925
29TCF4TCF4, IVS9AS, G-C, -1SNVPathogenic
30TCF4NM_ 001083962.1(TCF4): c.1733G> C (p.Arg578Pro)SNVPathogenicrs121909123GRCh37Chr 18, 52896224: 52896224
31TCF4TCF4, 1-BP DEL, 908CdeletionPathogenic
32TCF4NM_ 001083962.1(TCF4): c.1086G> A (p.Trp362Ter)SNVPathogenicrs398123560GRCh37Chr 18, 52924606: 52924606
33TCF4NM_ 001083962.1(TCF4): c.1733G> A (p.Arg578His)SNVPathogenicrs121909123GRCh37Chr 18, 52896224: 52896224
34TCF4NM_ 001083962.1(TCF4): c.514_ 517delAAAG (p.Lys172Phefs)deletionPathogenicrs398123561GRCh37Chr 18, 53017622: 53017625

Copy number variations for Pitt-Hopkins Syndrome from CNVD:

6
id CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1122008185110812151312629DeletionTCF4Pitt-Hopkins syndrome

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
19.6CNTNAP2, NRXN1

GO Terms for genes affiliated with Pitt-Hopkins Syndrome

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

idNameGO IDScoreTop Affiliating Genes
1synapseGO:00452028.6CDKL5, NRXN1, SLC9A6

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

idNameGO IDScoreTop Affiliating Genes
1adult behaviorGO:003053410.2CNTNAP2, NRXN1
2learningGO:000761210.1CNTNAP2, NRXN1
3social behaviorGO:003517610.0CNTNAP2, NRXN1
4vocal learningGO:00422979.9CNTNAP2, NRXN1
5vocalization behaviorGO:00716259.6CNTNAP2, NRXN1

Sources for Pitt-Hopkins Syndrome

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2CDC
6CNVD
10DGIdb
15ExPASy
16FDA
17FMA
27GTR
28HGMD
29HMDB
30ICD10
31ICD10 via Orphanet
32ICD9CM
33IUPHAR
34KEGG
37MedGen
39MeSH
40MESH via Orphanet
41MGI
44NCI
45NCIt
46NDF-RT
49NINDS
50Novoseek
52OMIM
53OMIM via Orphanet
57PubMed
58QIAGEN
63SNOMED-CT via Orphanet
67Tumor Gene Family of Databases
68UMLS
69UMLS via Orphanet