PTHS
MCID: PTT014
MIFTS: 60

Pitt-Hopkins Syndrome (PTHS)

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

Aliases & Classifications for Pitt-Hopkins Syndrome

MalaCards integrated aliases for Pitt-Hopkins Syndrome:

Name: Pitt-Hopkins Syndrome 56 12 74 24 52 25 58 73 36 29 13 6 43 15 39 71
Pths 56 25 73
Intellectual Disability, Wide Mouth, Distinctive Facial Features, and Intermittent Hyperventilation Followed by Apnea 52
Mental Retardation, Syndromal, with Intermittent Hyperventilation 56
Mental Retardation Syndromal with Intermittent Hyperventilation 73
Encephalopathy, Severe Epileptic, with Autonomic Dysfunction 56
Encephalopathy Severe Epileptic with Autonomic Dysfunction 73
Pitt Hopkins Syndrome 52
Mesh; D006985 73
Mesh; D008607 73
Phs 25

Characteristics:

Orphanet epidemiological data:

58
pitt-hopkins syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal dominant


HPO:

31
pitt-hopkins syndrome:
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance Penetrance of a pathogenic tcf4 allele is complete, though some phenotypic variability is seen among sibs born to a presumably mosaic parent.

Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Pitt-Hopkins Syndrome

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. People with Pitt-Hopkins syndrome have moderate to severe intellectual disability. Most affected individuals have delayed development of mental and motor skills (psychomotor delay). They are delayed in learning to walk and developing fine motor skills such as picking up small items with their fingers. People with Pitt-Hopkins syndrome typically do not develop speech; some may learn to say a few words. Many affected individuals exhibit features of autistic spectrum disorders, which are characterized by impaired communication and socialization skills. Breathing problems in individuals with Pitt-Hopkins syndrome are characterized by episodes of rapid breathing (hyperventilation) followed by periods in which breathing slows or stops (apnea). These episodes can cause a lack of oxygen in the blood, leading to a bluish appearance of the skin or lips (cyanosis). In some cases, the lack of oxygen can cause loss of consciousness. Some older individuals with Pitt-Hopkins syndrome develop widened and rounded tips of the fingers and toes (clubbing) because of recurrent episodes of decreased oxygen in the blood. The breathing problems occur only when the person is awake and typically first appear in mid-childhood, but they can begin as early as infancy. Episodes of hyperventilation and apnea can be triggered by emotions such as excitement or anxiety or by extreme tiredness (fatigue). Epilepsy occurs in most people with Pitt-Hopkins syndrome and usually begins during childhood, although it can be present from birth. Individuals with Pitt-Hopkins syndrome have distinctive facial features that include thin eyebrows, sunken eyes, a prominent nose with a high nasal bridge, a pronounced double curve of the upper lip (Cupid's bow), a wide mouth with full lips, and widely spaced teeth. The ears are usually thick and cup-shaped. Children with Pitt-Hopkins syndrome typically have a happy, excitable demeanor with frequent smiling, laughter, and hand-flapping movements. However, they can also experience anxiety and behavioral problems. Other features of Pitt-Hopkins syndrome may include constipation and other gastrointestinal problems, an unusually small head (microcephaly), nearsightedness (myopia), eyes that do not look in the same direction (strabismus), short stature, and minor brain abnormalities. Affected individuals may also have small hands and feet, a single crease across the palms of the hands, flat feet (pes planus), or unusually fleshy pads at the tips of the fingers and toes. Males with Pitt-Hopkins syndrome may have undescended testes (cryptorchidism).

MalaCards based summary : Pitt-Hopkins Syndrome, also known as pths, is related to pitt-hopkins-like syndrome 1 and pitt-hopkins-like syndrome, and has symptoms including seizures, constipation and nasal flaring. An important gene associated with Pitt-Hopkins Syndrome is TCF4 (Transcription Factor 4), and among its related pathways/superpathways is Cell adhesion molecules (CAMs). The drugs Magnesium citrate and Sodium citrate have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and eye, and related phenotypes are short neck and muscular hypotonia

Disease Ontology : 12 A syndrome characterized by intellectual disability and developmental delay, breathing problems, recurrent seizures, and distinctive facial features and that has material basis in heterozygous de novo mutations in the TCF4 gene in chromosome 18q21.

NIH Rare Diseases : 52 Pitt-Hopkins syndrome (PTHS) is a genetic syndrome that causes developmental delays, moderate to severe intellectual disability , behavioral differences, distinctive facial features, and breathing problems such as episodes of rapid breathing (hyperventilation ) and breath-holding. Other features may include symptoms of autism spectrum disorder, sleep disturbances, seizures , constipation, nearsightedness, and minor skeletal abnormalities. PTHS is caused by a mutation in the TCF4 gene , or by a loss (deletion ) of the part of chromosome 18 that contains the TCF4 gene. Inheritance is autosomal dominant , but PTHS typically is not inherited from a parent, occurring sporadically due to a new mutation in people with no family history of PTHS. The diagnosis may be suspected based on signs and symptoms and can be confirmed with genetic testing . There is no cure for PTHS, but there are ways to manage or improve many of the signs and symptoms. Management may include early intervention services for infants and young children, an individualized education plan for school-aged children, behavioral therapy, and routine treatment of seizures, nearsightedness, constipation, and skeletal abnormalities.

OMIM : 56 The Pitt-Hopkins syndrome is characterized by mental retardation, wide mouth and distinctive facial features, and intermittent hyperventilation followed by apnea (Zweier et al., 2007). See also Pitt-Hopkins-like syndrome-1 (610042), caused by mutation in the CNTNAP2 gene (604569) on chromosome 7q35, and Pitt-Hopkins-like syndrome-2 (600565), caused by mutation in the NRXN1 gene (600565) on chromosome 2p16.3. (610954)

KEGG : 36 Pitt-Hopkins Syndrome (PHS) is a rare disorder of severe mental retardation. Facial dysmorphism include a beaked nose, flared nostrils, and a wide mouth with a 'cupid's-bow' shaped upper lip. A particular breathing pattern is characteristic of PHS. The defective gene is TCF4 in PHS, and in patients who show severe mental retardation and other features resembling PHS have mutations in CNTNAP2 and Neurexin I.

UniProtKB/Swiss-Prot : 73 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.

Wikipedia : 74 Pitt-Hopkins syndrome (PTHS) is a rare genetic disorder characterized by developmental delay, epilepsy,... more...

GeneReviews: NBK100240

Related Diseases for Pitt-Hopkins Syndrome

Diseases in the Pitt-Hopkins Syndrome family:

Pitt-Hopkins-Like Syndrome 1 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 1516)
# Related Disease Score Top Affiliating Genes
1 pitt-hopkins-like syndrome 1 33.6 NRXN1 MECP2 CNTNAP2
2 pitt-hopkins-like syndrome 31.1 NRXN1 CNTNAP2
3 seizure disorder 30.8 MECP2 CDKL5
4 angelman syndrome 30.3 UBE3A TCF4 SLC9A7 SLC9A6 MECP2 CDKL5
5 alacrima, achalasia, and mental retardation syndrome 30.2 UBE3A TCF4 SLC9A6 NRXN1 MECP2 IQSEC2
6 rett syndrome 30.0 UBE3A TCF4 MECP2 FOXG1 CDKL5 ANKRD31
7 syndromic intellectual disability 29.8 TCF4 SLC9A7 SLC9A6 MECP2 IQSEC2
8 autism spectrum disorder 29.6 ZNF804A UBE3A NRXN1 MECP2 MBD5 IQSEC2
9 schizophrenia 29.5 ZNF804A TCF4 NRXN1 MECP2 MBD5 EHMT1
10 mowat-wilson syndrome 29.4 UBE3A SLC9A7 SLC9A6 MECP2 MBD5 FOXG1
11 fragile x syndrome 29.3 UBE3A NRXN1 MECP2 CNTNAP2
12 focal epilepsy 29.1 MECP2 CNTNAP2 CDKL5
13 bruxism 28.8 UBE3A MECP2 IQSEC2 FOXG1 CDKL5
14 christianson syndrome 28.1 UBE3A SLC9A7 SLC9A6 MECP2 MBD5 FOXG1
15 autism 27.2 ZNF804A UBE3A TCF4 NRXN1 MECP2 MBD5
16 pallister-hall syndrome 12.2
17 hypoparathyroidism, familial isolated 12.1
18 pseudohypoparathyroidism, type ib 11.9
19 pulmonary hypertension 11.8
20 paroxysmal hemicrania 11.8
21 pitt-hopkins-like syndrome 2 11.7
22 pseudohypoparathyroidism, type ia 11.7
23 leukemia, chronic myeloid 11.7
24 hyperparathyroidism, neonatal severe 11.7
25 pseudohypoparathyroidism, type ii 11.7
26 distal renal tubular acidosis 11.6
27 gastroesophageal reflux 11.6
28 parathyroid carcinoma 11.6
29 chondrodysplasia, blomstrand type 11.5
30 hyperparathyroidism 1 11.5
31 mucolipidosis ii alpha/beta 11.5
32 metabolic acidosis 11.5
33 hyperoxaluria, primary, type iii 11.4
34 lactic acidosis 11.4
35 helicobacter pylori infection 11.4
36 metaphyseal chondrodysplasia, jansen type 11.4
37 rickets 11.4
38 pheochromocytoma 11.4
39 hyperuricemia 11.4
40 bartter disease 11.4
41 renal tubular acidosis, proximal 11.4
42 osteopetrosis 11.4
43 chronic thromboembolic pulmonary hypertension 11.4
44 hypophosphatemic rickets, x-linked dominant 11.4
45 hyperphenylalaninemia, bh4-deficient, d 11.4
46 pulmonary hypertension owing to lung disease and/or hypoxia 11.4
47 hypomagnesemia 1, intestinal 11.3
48 inclusion-cell disease 11.2
49 acid sphingomyelinase deficiency 11.2
50 pulmonary hypertension with unclear multifactorial mechanism 11.2

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



Diseases related to Pitt-Hopkins Syndrome

Symptoms & Phenotypes for Pitt-Hopkins Syndrome

Human phenotypes related to Pitt-Hopkins Syndrome:

58 31 (show top 50) (show all 85)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000470
2 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001252
3 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
4 constipation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002019
5 dysphasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002357
6 coarse facial features 58 31 hallmark (90%) Very frequent (99-80%) HP:0000280
7 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
8 pes planus 58 31 hallmark (90%) Very frequent (99-80%) HP:0001763
9 thick vermilion border 58 31 hallmark (90%) Very frequent (99-80%) HP:0012471
10 feeding difficulties 58 31 hallmark (90%) Very frequent (99-80%) HP:0011968
11 intellectual disability, moderate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002342
12 microcephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000252
13 anteverted nares 58 31 hallmark (90%) Very frequent (99-80%) HP:0000463
14 gastroesophageal reflux 58 31 hallmark (90%) Very frequent (99-80%) HP:0002020
15 full cheeks 58 31 hallmark (90%) Very frequent (99-80%) HP:0000293
16 short philtrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000322
17 narrow forehead 58 31 hallmark (90%) Very frequent (99-80%) HP:0000341
18 specific learning disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001328
19 myopia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000545
20 aphasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002381
21 prominent nasal bridge 58 31 hallmark (90%) Very frequent (99-80%) HP:0000426
22 wide mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000154
23 deeply set eye 58 31 hallmark (90%) Very frequent (99-80%) HP:0000490
24 small hand 58 31 hallmark (90%) Very frequent (99-80%) HP:0200055
25 overhanging nasal tip 58 31 hallmark (90%) Very frequent (99-80%) HP:0011833
26 upslanted palpebral fissure 58 31 hallmark (90%) Very frequent (99-80%) HP:0000582
27 echolalia 58 31 hallmark (90%) Very frequent (99-80%) HP:0010529
28 esophagitis 58 31 hallmark (90%) Very frequent (99-80%) HP:0100633
29 abnormal palate morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0000174
30 thickened helices 58 31 hallmark (90%) Very frequent (99-80%) HP:0000391
31 hiatus hernia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002036
32 tapered finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0001182
33 astigmatism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000483
34 finger clinodactyly 58 31 hallmark (90%) Very frequent (99-80%) HP:0040019
35 misalignment of teeth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000692
36 single transverse palmar crease 58 31 hallmark (90%) Very frequent (99-80%) HP:0000954
37 pes valgus 58 31 hallmark (90%) Very frequent (99-80%) HP:0008081
38 short metatarsal 58 31 hallmark (90%) Very frequent (99-80%) HP:0010743
39 mutism 58 31 hallmark (90%) Very frequent (99-80%) HP:0002300
40 failure of eruption of permanent teeth 58 31 hallmark (90%) Very frequent (99-80%) HP:0006352
41 broad fingertip 58 31 hallmark (90%) Very frequent (99-80%) HP:0011300
42 seizures 58 31 frequent (33%) Frequent (79-30%) HP:0001250
43 sleep apnea 58 31 frequent (33%) Frequent (79-30%) HP:0010535
44 acrocyanosis 58 31 frequent (33%) Frequent (79-30%) HP:0001063
45 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
46 absent speech 58 31 frequent (33%) Frequent (79-30%) HP:0001344
47 gait ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0002066
48 narrow foot 58 31 frequent (33%) Frequent (79-30%) HP:0001786
49 aplasia/hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0007370
50 small cerebral cortex 58 31 frequent (33%) Frequent (79-30%) HP:0002472

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Neck:
short neck

Neurologic Central Nervous System:
seizures
incoordination
hypotonia
delayed motor development
mental retardation, severe
more
Head And Neck Teeth:
widely spaced teeth

Genitourinary Internal Genitalia Male:
cryptorchidism

Head And Neck Face:
full cheeks
short philtrum
square forehead
coarse face
bitemporal narrowing
more
Respiratory:
hyperventilation
abnormal breathing patterns
intermittent breathing

Muscle Soft Tissue:
hypotonia

Genitourinary External Genitalia Male:
small penis

Head And Neck Mouth:
wide open mouth
cupid's bow upper lip
thick, fleshy lips

Skeletal Hands:
clinodactyly
simian crease
tapered fingers
small, slender palms
clubbing of the fingers
more
Abdomen Gastrointestinal:
constipation
gastroesophageal reflux

Skeletal Feet:
pes planus
pes valgus
slender feet
fetal pads

Head And Neck Head:
microcephaly

Head And Neck Eyes:
strabismus
myopia
astigmatism
deep-set eyes
upslanting palpebral fissures

Head And Neck Nose:
broad nasal bridge
beaked nasal bridge
downturned, pointed nasal tip
flaring nostrils

Head And Neck Ears:
cup-shaped ears
fleshy ears

Neurologic Behavioral Psychiatric Manifestations:
aggression
happy personality
sterotypical movements

Clinical features from OMIM:

610954

UMLS symptoms related to Pitt-Hopkins Syndrome:


seizures, constipation, nasal flaring

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

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased shRNA abundance (Z-score < -2) GR00366-A-148 9.36 CHD6
2 Decreased shRNA abundance (Z-score < -2) GR00366-A-15 9.36 CHD6
3 Decreased shRNA abundance (Z-score < -2) GR00366-A-17 9.36 CHD6 SPIB UBE3A
4 Decreased shRNA abundance (Z-score < -2) GR00366-A-175 9.36 UBE3A
5 Decreased shRNA abundance (Z-score < -2) GR00366-A-213 9.36 CHD6
6 Decreased shRNA abundance (Z-score < -2) GR00366-A-33 9.36 SPIB
7 Decreased shRNA abundance (Z-score < -2) GR00366-A-34 9.36 SPIB
8 Decreased shRNA abundance (Z-score < -2) GR00366-A-95 9.36 SPIB UBE3A

MGI Mouse Phenotypes related to Pitt-Hopkins Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.73 CDKL5 CHD6 CNTNAP2 EHMT1 FOXG1 MBD5
2 nervous system MP:0003631 9.36 CDKL5 CNTNAP2 EHMT1 FOXG1 MBD5 MECP2

Drugs & Therapeutics for Pitt-Hopkins Syndrome

Drugs for Pitt-Hopkins Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 14)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Magnesium citrate Approved Phase 2 3344-18-1
2
Sodium citrate Approved, Investigational Phase 2 68-04-2
3
Vancomycin Approved Phase 2 1404-90-6 441141 14969
4
Citric acid Approved, Nutraceutical, Vet_approved Phase 2 77-92-9 311
5
Calcium Approved, Nutraceutical Phase 2 7440-70-2 271
6 Anti-Infective Agents Phase 2
7 Gastrointestinal Agents Phase 2
8 Anticoagulants Phase 2
9 Cathartics Phase 2
10 Citrate Phase 2
11 Chelating Agents Phase 2
12 Anti-Bacterial Agents Phase 2
13 Calcium, Dietary Phase 2
14 Laxatives Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Microbiota Transfer Therapy for Children With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders Recruiting NCT04132427 Phase 2
2 Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Pitt-Hopkins Syndrome

Cochrane evidence based reviews: pitt-hopkins syndrome

Genetic Tests for Pitt-Hopkins Syndrome

Genetic tests related to Pitt-Hopkins Syndrome:

# Genetic test Affiliating Genes
1 Pitt-Hopkins Syndrome 29 TCF4

Anatomical Context for Pitt-Hopkins Syndrome

MalaCards organs/tissues related to Pitt-Hopkins Syndrome:

40
Brain, Testes, Eye, Skin, Cortex, Bone, Endothelial

Publications for Pitt-Hopkins Syndrome

Articles related to Pitt-Hopkins Syndrome:

(show top 50) (show all 198)
# Title Authors PMID Year
1
Further delineation of Pitt-Hopkins syndrome: phenotypic and genotypic description of 16 novel patients. 56 6 24 61
18728071 2008
2
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. 61 24 6 56
17436254 2007
3
Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome). 61 6 24 56
17436255 2007
4
Pitt-Hopkins syndrome in two patients and further definition of the phenotype. 61 24 6 56
16531728 2006
5
Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome: clinical score and further delineation of the TCF4 mutational spectrum. 24 56 61
22045651 2012
6
Fetal pads as a clue to the diagnosis of Pitt-Hopkins syndrome. 61 24 56
21671383 2011
7
The Pitt-Hopkins syndrome: report of 16 new patients and clinical diagnostic criteria. 61 24 56
21671391 2011
8
Genotype-phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations. 56 24 61
19938247 2009
9
Mutational, functional, and expression studies of the TCF4 gene in Pitt-Hopkins syndrome. 24 56 61
19235238 2009
10
Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome. 24 61 56
18627065 2008
11
Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4. 24 56 61
17478476 2007
12
Pitt-Hopkins Syndrome 6 61
22934316 2012
13
Possible case of Pitt-Hopkins syndrome in sibs. 56 61
11568923 2001
14
Mental retardation, "coarse" face, and hyperbreathing: confirmation of the Pitt-Hopkins syndrome. 56 61
9475596 1998
15
Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series. 24 61
29318938 2018
16
Impairment of different protein domains causes variable clinical presentation within Pitt-Hopkins syndrome and suggests intragenic molecular syndromology of TCF4. 24 61
28807867 2017
17
Tcf4 Regulates Synaptic Plasticity, DNA Methylation, and Memory Function. 24 61
27568567 2016
18
Partial deletion of TCF4 in three generation family with non-syndromic intellectual disability, without features of Pitt-Hopkins syndrome. 61 24
27132474 2016
19
Complex translocation disrupting TCF4 and altering TCF4 isoform expression segregates as mild autosomal dominant intellectual disability. 24 61
27179618 2016
20
Phenotype and natural history in 101 individuals with Pitt-Hopkins syndrome through an internet questionnaire system. 24 61
27072915 2016
21
Neurodevelopmental models of transcription factor 4 deficiency converge on a common ion channel as a potential therapeutic target for Pitt Hopkins syndrome. 61 24
28032012 2016
22
Successful use of acetazolamide for central apnea in a child with Pitt-Hopkins syndrome. 61 24
25900839 2015
23
Somatic mosaicism in a mother of two children with Pitt-Hopkins syndrome. 24 61
22335494 2013
24
Pitt-Hopkins syndrome in a boy with Charcot Marie Tooth disease type 1A: a rare co-occurrence of 2 genetic disorders. 61 24
22378661 2012
25
Clinical and polygraphic improvement of breathing abnormalities after valproate in a case of Pitt-Hopkins syndrome. 61 24
22378662 2012
26
Mosaic 18q21.2 deletions including the TCF4 gene: a clinical report. 24 61
23165966 2012
27
Development, cognition, and behaviour in Pitt-Hopkins syndrome. 61 24
22712893 2012
28
Acetazolamide for severe apnea in Pitt-Hopkins syndrome. 24 61
22407847 2012
29
Transcription factor 4 and myocyte enhancer factor 2C mutations are not common causes of Rett syndrome. 61 24
22383159 2012
30
Pitt-Hopkins syndrome should be in the differential diagnosis for males presenting with an ATR-X phenotype. 24 61
22040220 2011
31
Mosaic microdeletion 18q21 as a cause of mental retardation. 24 61
20813211 2010
32
Two percent of patients suspected of having Angelman syndrome have TCF4 mutations. 61 24
20184619 2010
33
Interstitial deletion of 18q: comparative genomic hybridization array analysis of 46, XX,del(18)(q21.2.q21.33). 61 24
19813260 2010
34
TCF4 deletions in Pitt-Hopkins Syndrome. 24 61
18781613 2008
35
Deletion 18q21.2q21.32 involving TCF4 in a boy diagnosed by CGH-array. 61 24
18222743 2008
36
European combined analysis of the CTG18.1 and the ERDA1 CAG/CTG repeats in bipolar disorder. 6
12032737 2002
37
Mental retardation, macrostomia and hyperpnoea syndrome. 56
8489799 1993
38
A syndrome of mental retardation, wide mouth and intermittent overbreathing. 56
728011 1978
39
Trinucleotide Repeat Expansion in the Transcription Factor 4 (TCF4) Gene Leads to Widespread mRNA Splicing Changes in Fuchs' Endothelial Corneal Dystrophy. 24
28118661 2017
40
Somatic mosaicism detected by exon-targeted, high-resolution aCGH in 10,362 consecutive cases. 24
24398791 2014
41
The role of the TCF4 gene in the phenotype of individuals with 18q segmental deletions. 24
21671075 2011
42
Functional diversity of human basic helix-loop-helix transcription factor TCF4 isoforms generated by alternative 5' exon usage and splicing. 24
21789225 2011
43
The E-protein Tcf4 interacts with Math1 to regulate differentiation of a specific subset of neuronal progenitors. 24
17878293 2007
44
Basic helix-loop-helix factors in cortical development. 24
12848929 2003
45
Enhancer-specific modulation of E protein activity. 24
11724804 2002
46
HASH-1 and E2-2 are expressed in human neuroblastoma cells and form a functional complex. 24
10903890 2000
47
Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. 24
10611221 2000
48
Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system. 24
9388783 1997
49
A natural classification of the basic helix-loop-helix class of transcription factors. 24
9144210 1997
50
B-lymphocyte development is regulated by the combined dosage of three basic helix-loop-helix genes, E2A, E2-2, and HEB. 24
8649400 1996

Variations for Pitt-Hopkins Syndrome

ClinVar genetic disease variations for Pitt-Hopkins Syndrome:

6 (show top 50) (show all 231) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TCF4 NM_001083962.2(TCF4):c.1153C>T (p.Arg385Ter)SNV Pathogenic 7372 rs121909122 18:52921925-52921925 18:55254694-55254694
2 TCF4 TCF4, IVS9AS, G-C, -1SNV Pathogenic 7373
3 TCF4 NM_001083962.2(TCF4):c.1733G>C (p.Arg578Pro)SNV Pathogenic 7374 rs121909123 18:52896224-52896224 18:55228993-55228993
4 TCF4 NM_001083962.2(TCF4):c.908del (p.Thr303fs)deletion Pathogenic 7375 18:52937076-52937076 18:55269845-55269845
5 TCF4 NM_001083962.2(TCF4):c.1738C>T (p.Arg580Trp)SNV Pathogenic 7370 rs121909120 18:52896219-52896219 18:55228988-55228988
6 TCF4 NM_001083962.2(TCF4):c.1733G>A (p.Arg578His)SNV Pathogenic 93542 rs121909123 18:52896224-52896224 18:55228993-55228993
7 TCF4 NM_001083962.2(TCF4):c.1498G>T (p.Gly500Ter)SNV Pathogenic 160078 rs587784459 18:52899891-52899891 18:55232660-55232660
8 TCF4 NM_001083962.2(TCF4):c.1146+1G>ASNV Pathogenic 160076 rs587784458 18:52924545-52924545 18:55257314-55257314
9 TCF4 NM_001083962.2(TCF4):c.991-2A>GSNV Pathogenic 160093 rs587784470 18:52927260-52927260 18:55260029-55260029
10 TCF4 NM_001083962.2(TCF4):c.791del (p.Ser264fs)deletion Pathogenic 160090 rs587784468 18:52937193-52937193 18:55269962-55269962
11 TCF4 NM_001083962.2(TCF4):c.656-1G>CSNV Pathogenic 160087 rs587784466 18:52942984-52942984 18:55275753-55275753
12 TCF4 NM_001083962.2(TCF4):c.655+1G>ASNV Pathogenic 160086 rs587784465 18:52946781-52946781 18:55279550-55279550
13 TCF4 NM_001083962.2(TCF4):c.469C>T (p.Arg157Ter)SNV Pathogenic 160085 rs587784464 18:53018135-53018135 18:55350904-55350904
14 TCF4 NM_001083962.2(TCF4):c.415del (p.Leu139fs)deletion Pathogenic 160084 rs587784463 18:53018189-53018189 18:55350958-55350958
15 TCF4 NM_001083962.2(TCF4):c.655+1G>TSNV Pathogenic 167729 rs587784465 18:52946781-52946781 18:55279550-55279550
16 TCF4 NM_001083962.2(TCF4):c.1438C>T (p.Gln480Ter)SNV Pathogenic 180214 rs727505396 18:52901827-52901827 18:55234596-55234596
17 TCF4 NM_001083962.2(TCF4):c.1570C>T (p.Gln524Ter)SNV Pathogenic 207534 rs796053418 18:52899819-52899819 18:55232588-55232588
18 TCF4 NM_001083962.2(TCF4):c.968C>T (p.Ala323Val)SNV Pathogenic 208487 rs797045003 18:52928719-52928719 18:55261488-55261488
19 TCF4 NM_001083962.2(TCF4):c.1069+1G>TSNV Pathogenic 209195 rs797045072 18:52927179-52927179 18:55259948-55259948
20 TCF4 NM_001083962.2(TCF4):c.1411C>T (p.Gln471Ter)SNV Pathogenic 212377 rs797046033 18:52901854-52901854 18:55234623-55234623
21 TCF4 NM_001083962.2(TCF4):c.655+1_655+2dupduplication Pathogenic 212381 rs797046036 18:52946779-52946780 18:55279548-55279549
22 TCF4 NM_001083962.2(TCF4):c.978delinsGG (p.Ala327fs)indel Pathogenic 212724 rs863223404 18:52928709-52928709 18:55261478-55261478
23 TCF4 NM_001083962.2(TCF4):c.520C>T (p.Arg174Ter)SNV Pathogenic 235853 rs878853149 18:53017619-53017619 18:55350388-55350388
24 TCF4 NM_001083962.2(TCF4):c.1719_1722dup (p.Ala575fs)duplication Pathogenic 374031 rs1057518848 18:52896235-52896238 18:55229004-55229007
25 TCF4 NM_001083962.2(TCF4):c.1953_1954TC[2] (p.Ser653fs)short repeat Pathogenic 431137 rs1135401807 18:52895514-52895515 18:55228283-55228284
26 TCF4 NM_001083962.2(TCF4):c.1504del (p.Gln502fs)deletion Pathogenic 468948 rs1555718426 18:52899885-52899885 18:55232654-55232654
27 TCF4 NM_001083962.2(TCF4):c.1834del (p.His612fs)deletion Pathogenic 436963 rs1555710069 18:52896123-52896123 18:55228892-55228892
28 TCF4 NC_000018.9:g.(?_52895436)_(53303148_?)deldeletion Pathogenic 468945 18:52895436-53303148 18:55228205-55635917
29 TCF4 NM_001083962.2(TCF4):c.1557del (p.Asp520fs)deletion Pathogenic 468949 rs1555717982 18:52899832-52899832 18:55232601-55232601
30 TCF4 NM_001083962.2(TCF4):c.919_922+2delinsGTCCCindel Pathogenic 545571 rs1555789019 18:52937060-52937065 18:55269829-55269834
31 TCF4 NM_001083962.2(TCF4):c.1292del (p.Gly431fs)deletion Pathogenic 561127 rs1568471940 18:52921785-52921786 18:55254555-55254555
32 TCF4 NM_001083962.2(TCF4):c.1034del (p.Pro345fs)deletion Pathogenic 561126 rs1568509890 18:52927214-52927215 18:55259984-55259984
33 TCF4 NM_001083962.2(TCF4):c.937_941del (p.Gly313fs)deletion Pathogenic 561128 rs1568523662 18:52928745-52928750 18:55261515-55261519
34 TCF4 NM_001083962.2(TCF4):c.696del (p.Gly232_Met233insTer)deletion Pathogenic 562214 rs1568622225 18:52942943-52942943 18:55275712-55275712
35 TCF4 NM_001083962.2(TCF4):c.740_741AT[1] (p.Ile248fs)short repeat Pathogenic 565375 rs1568620706 18:52942896-52942897 18:55275665-55275666
36 TCF4 NM_001083962.2(TCF4):c.1527del (p.Ser510fs)deletion Pathogenic 574899 rs1568331766 18:52899862-52899862 18:55232631-55232631
37 TCF4 NM_001083962.2(TCF4):c.1146+3A>GSNV Pathogenic 565600 rs1568490874 18:52924543-52924543 18:55257312-55257312
38 TCF4 NM_001083962.2(TCF4):c.1552G>T (p.Glu518Ter)SNV Pathogenic 577819 rs1555718063 18:52899837-52899837 18:55232606-55232606
39 TCF4 NM_001083962.2(TCF4):c.1705C>T (p.Arg569Trp)SNV Pathogenic 620020 rs1568305976 18:52896252-52896252 18:55229021-55229021
40 TCF4 NM_001083962.2(TCF4):c.1486+2T>GSNV Pathogenic 626271 rs1555721921 18:52901777-52901777 18:55234546-55234546
41 TCF4 NM_001083962.2(TCF4):c.1328C>G (p.Ser443Ter)SNV Pathogenic 661273 18:52921750-52921750 18:55254519-55254519
42 TCF4 NM_001083962.2(TCF4):c.593_602delinsGCCGACTACAATAGGGAC (p.Ser198_Tyr201delinsCysArgLeuGlnTer)indel Pathogenic 663924 18:52946835-52946844 18:55279604-55279613
43 TCF4 NM_001083962.2(TCF4):c.740dup (p.His247fs)duplication Pathogenic 569100 rs1568620774 18:52942899-52942899 18:55275668-55275668
44 TCF4 NM_001083962.2(TCF4):c.923-2A>GSNV Pathogenic 656789 18:52928766-52928766 18:55261535-55261535
45 TCF4 NM_001083962.2(TCF4):c.1726C>T (p.Arg576Ter)SNV Pathogenic/Likely pathogenic 488988 rs1555710726 18:52896231-52896231 18:55229000-55229000
46 TCF4 NM_001083962.2(TCF4):c.1876C>T (p.Arg626Ter)SNV Pathogenic/Likely pathogenic 430016 rs1131691735 18:52896081-52896081 18:55228850-55228850
47 TCF4 NM_001083962.2(TCF4):c.1965dup (p.Gly656fs)duplication Pathogenic/Likely pathogenic 212379 rs797046035 18:52895507-52895507 18:55228276-55228276
48 TCF4 NM_001083962.2(TCF4):c.990G>A (p.Ser330=)SNV Pathogenic/Likely pathogenic 160092 rs587784469 18:52928697-52928697 18:55261466-55261466
49 TCF4 NM_001083962.2(TCF4):c.1739G>A (p.Arg580Gln)SNV Pathogenic/Likely pathogenic 7371 rs121909121 18:52896218-52896218 18:55228987-55228987
50 TCF4 NM_001083962.2(TCF4):c.1840G>C (p.Ala614Pro)SNV Likely pathogenic 160081 rs587784462 18:52896117-52896117 18:55228886-55228886

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

73 (show all 13)
# Symbol AA change Variation ID SNP ID
1 TCF4 p.Arg576Gln VAR_034704 rs121909121
2 TCF4 p.Arg576Trp VAR_034705 rs121909120
3 TCF4 p.Asp535Gly VAR_058632
4 TCF4 p.Arg572Gly VAR_058633
5 TCF4 p.Ala610Val VAR_058634
6 TCF4 p.Gly358Val VAR_066839
7 TCF4 p.Arg574Pro VAR_066840 rs121909123
8 TCF4 p.Arg578His VAR_066841
9 TCF4 p.Arg565Trp VAR_066970
10 TCF4 p.Arg572Gln VAR_066971 rs105752107
11 TCF4 p.Arg574His VAR_066972 rs121909123
12 TCF4 p.Arg578Pro VAR_066973
13 TCF4 p.Ala583Pro VAR_066974

Copy number variations for Pitt-Hopkins Syndrome from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 122008 18 51108121 51312629 Deletion TCF4 Pitt-Hopkins syndrome

Expression for Pitt-Hopkins Syndrome

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

Pathways for Pitt-Hopkins Syndrome

Pathways related to Pitt-Hopkins Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 Cell adhesion molecules (CAMs) hsa04514

GO Terms for Pitt-Hopkins Syndrome

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

# Name GO ID Score Top Affiliating Genes
1 neuron projection development GO:0031175 9.65 NRXN1 MECP2 CNTNAP2
2 brain development GO:0007420 9.56 UBE3A MECP2 FOXG1 CNTNAP2
3 positive regulation of neuron differentiation GO:0045666 9.54 TCF4 TCF12 FOXG1
4 histone methylation GO:0016571 9.46 MECP2 EHMT1
5 regulation of pH GO:0006885 9.43 SLC9A7 SLC9A6
6 sodium ion import across plasma membrane GO:0098719 9.4 SLC9A7 SLC9A6
7 learning GO:0007612 9.33 NRXN1 MECP2 CNTNAP2
8 vocalization behavior GO:0071625 9.32 NRXN1 CNTNAP2
9 vocal learning GO:0042297 8.96 NRXN1 CNTNAP2
10 social behavior GO:0035176 8.8 NRXN1 MECP2 CNTNAP2

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

# Name GO ID Score Top Affiliating Genes
1 bHLH transcription factor binding GO:0043425 9.26 TCF4 TCF12
2 solute:proton antiporter activity GO:0015299 9.16 SLC9A7 SLC9A6
3 sodium:proton antiporter activity GO:0015385 8.96 SLC9A7 SLC9A6
4 potassium:proton antiporter activity GO:0015386 8.62 SLC9A7 SLC9A6

Sources for Pitt-Hopkins 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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