Pitt-Hopkins syndrome

Pitt-Hopkins syndrome (PHS) is characterized by the association of intellectual deficit, characteristic facial dysmorphism and problems of abnormal and irregular breathing.



Input patient's signs and symptoms


Narrow down the case reports



Total: 21 (papers)

   


(per page)
Matched Phenotype  Gene  Mutation  MeSH
Rank
(Similarity)		 PMID
(PMCID)
1
(58.5%)		 19813260
 Interstitial deletion of 18q: comparative genomic hybridization array analysis of 46, XX,del(18)(q21.2.q21.33).
Kato Z, Morimoto W, Kimura T, Matsushima A, Kondo N.
Birth Defects Res A Clin Mol Teratol. 2010;88(2):132-5.
Short philtrum Abnormality of the hand
MBD1 MBD2
Basic Helix-Loop-Helix Leucine Zipper Transcriptio... Chromosome Deletion Chromosomes, Human, Pair 18 Craniofacial Abnormalities DNA-Binding Proteins Developmental Disabilities Females Genetic Association Studies Homo sapiens Intellectual Disability Oligonucleotide Array Sequence Analysis Psychomotor Disorders Rett Syndrome Syndrome Transcription Factor 4
2
(51.5%)		 16531728
 Pitt-Hopkins syndrome in two patients and further definition of the phenotype.
Peippo MM, Simola KO, Valanne LK, Larsen AT, Kahkonen M, Auranen MP, Ignatius J.
Clin Dysmorphol. 2006;15(2):47-54.
Wide mouth Microcephaly Clubbing
rs121909120
Child Child, Preschool Congenital Foot Deformity Congenital Hand Deformities Electroencephalography Homo sapiens Infant Magnetic Resonance Imaging Male Nervous System Physiological Phenomena Phenotype Syndrome
3
(41.7%)		 18627065
 Disruption of the TCF4 gene in a girl with mental retardation but without the classical Pitt-Hopkins syndrome.
Kalscheuer VM, Feenstra I, Van Ravenswaaij-Arts CM, Smeets DF, Menzel C, Ullmann R, Musante L, Ropers HH.
Am J Med Genet A. 2008;146A(16):2053-9.
Wide mouth Microcephaly
CHD6 TCF4
rs1057521070 rs1555710171 rs1555710416 rs1555721921 rs1555763998 rs1555764170 rs1555778204 rs1555797231 rs1555797248
Basic Helix-Loop-Helix Leucine Zipper Transcriptio... Child, Preschool Chromosomes, Human, Pair 18 Chromosomes, Human, Pair 20 DNA-Binding Proteins Face Females Fluorescent in Situ Hybridization Homo sapiens Intellectual Disability Oligonucleotide Array Sequence Analysis Phenotype Reverse Transcriptase Polymerase Chain Reaction Syndrome TCF Transcription Factors Transcription Factor 4
4
(39.0%)		 22378661
 Pitt-Hopkins syndrome in a boy with Charcot Marie Tooth disease type 1A: a rare co-occurrence of 2 genetic disorders.
Ghosh PS, Friedman NR, Ghosh D.
J Child Neurol. 2012;27(12):1602-6.
Microcephaly
Basic Helix-Loop-Helix Leucine Zipper Transcriptio... Charcot-Marie-Tooth Disease Electroencephalography Facies Homo sapiens Hyperventilation Infant Intellectual Disability Magnetic Resonance Imaging Male Transcription Factor 4
4
(39.0%)		 20813211
 Mosaic microdeletion 18q21 as a cause of mental retardation.
Stavropoulos DJ, MacGregor DL, Yoon G.
Eur J Med Genet. 2010;53(6):396-9.
Microcephaly
TCF4
Basic Helix-Loop-Helix Leucine Zipper Transcriptio... Child Chromosomes, Human, Pair 18 Cytogenetic Analysis Facies Females Gene Deletion Homo sapiens Hyperventilation Intellectual Disability Microcephaly Transcription Factor 4
6
(36.8%)		 17478476
 Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4.
Brockschmidt A, Todt U, Ryu S, Hoischen A, Landwehr C, Birnbaum S, Frenck W, Radlwimmer B, Lichter P, Engels H, Driever W, Kubisch C, Weber RG.
Hum Mol Genet. 2007;16(12):1488-94.
Wide mouth Hypotonia
rs1057521070 rs1555710171 rs1555710416 rs1555721921 rs1555763998 rs1555764170 rs1555778204 rs1555797231 rs1555797248
Animals Basic Helix-Loop-Helix Leucine Zipper Transcriptio... Child Cytogenetic Analysis DNA-Binding Proteins Face Females Haplotypes Homo sapiens Hyperventilation Intellectual Disability Language Development Disorders Models, Genetic Mutation Syndrome TCF Transcription Factors Transcription Factor 4 Zebrafish
7
(27.8%)		 21671383
 Fetal pads as a clue to the diagnosis of Pitt-Hopkins syndrome.
Lehalle D, Williams C, Siu VM, Clayton-Smith J.
Am J Med Genet A. 2011;155A(7):1685-9.
Wide mouth
TCF4
Basic Helix-Loop-Helix Leucine Zipper Transcriptio... Child Child, Preschool Facies Females Fingers Homo sapiens Hyperventilation Intellectual Disability Male Mutation Phenotype Toes Transcription Factor 4
7
(27.8%)		 20184619
 Two percent of patients suspected of having Angelman syndrome have TCF4 mutations.
Takano K, Lyons M, Moyes C, Jones J, Schwartz CE.
Clin Genet. 2010;78(3):282-8.
Wide mouth
TCF4 UBE3A
p|FS|S|384|T|7 p|SUB|R|582|P
Angelman Syndrome Base Sequence Basic Helix-Loop-Helix Leucine Zipper Transcriptio... Child DNA Mutational Analysis Homo sapiens Male Missense Mutation Mutation Transcription Factor 4
9
(26.3%)		 11568923
 Possible case of Pitt-Hopkins syndrome in sibs.
Orrico A, Galli L, Zappella M, Lam CW, Bonifacio S, Torricelli F, Hayek G.
Am J Med Genet. 2001;103(2):157-9.
Coarse facial features
Adult Craniofacial Abnormalities Females Growth Disorders Homo sapiens Hyperventilation Intellectual Disability Male Syndrome
10
(4.0%)		 29604340
 A case of Pitt-hopkins Syndrome with de novo mutation in TCF4: Clinical features and treatment for epilepsy.
Liu Y, Guo Y, Liu P, Li F, Yang C, Song J, Hu J, Xin D, Chen Z.
Int J Dev Neurosci. 2018;67:51-54.
Cyanosis
TCF4
p|SUB|R|728|X
Anticonvulsants Child, Preschool Epilepsy Facies Females Homo sapiens Hyperventilation Intellectual Disability Magnetic Resonance Imaging Mutation Transcription Factor 4
        

Phenotype(s) retrieved from Orphanet

    Total: 70

HPO ID Term Frequency
HP:0000154 Wide mouth Very frequent (99-80%)
HP:0000174 Abnormal palate morphology Very frequent (99-80%)
HP:0000252 Microcephaly Very frequent (99-80%)
HP:0000280 Coarse facial features Very frequent (99-80%)
HP:0000293 Full cheeks Very frequent (99-80%)
HP:0000322 Short philtrum Very frequent (99-80%)
HP:0000341 Narrow forehead Very frequent (99-80%)
HP:0000391 Thickened helices Very frequent (99-80%)
HP:0000426 Prominent nasal bridge Very frequent (99-80%)
HP:0000463 Anteverted nares Very frequent (99-80%)
HP:0000470 Short neck Very frequent (99-80%)
HP:0000483 Astigmatism Very frequent (99-80%)
HP:0000490 Deeply set eye Very frequent (99-80%)
HP:0000545 Myopia Very frequent (99-80%)
HP:0000582 Upslanted palpebral fissure Very frequent (99-80%)
HP:0000692 Misalignment of teeth Very frequent (99-80%)
HP:0000954 Single transverse palmar crease Very frequent (99-80%)
HP:0001182 Tapered finger Very frequent (99-80%)
HP:0001249 Intellectual disability Very frequent (99-80%)
HP:0001251 Ataxia Very frequent (99-80%)
HP:0001252 Muscular hypotonia Very frequent (99-80%)
HP:0001263 Global developmental delay Very frequent (99-80%)
HP:0001328 Specific learning disability Very frequent (99-80%)
HP:0001508 Failure to thrive Very frequent (99-80%)
HP:0001510 Growth delay Very frequent (99-80%)
HP:0001763 Pes planus Very frequent (99-80%)
HP:0002019 Constipation Very frequent (99-80%)
HP:0002020 Gastroesophageal reflux Very frequent (99-80%)
HP:0002036 Hiatus hernia Very frequent (99-80%)
HP:0002300 Mutism Very frequent (99-80%)
HP:0002342 Intellectual disability, moderate Very frequent (99-80%)
HP:0002357 Dysphasia Very frequent (99-80%)
HP:0002360 Sleep disturbance Very frequent (99-80%)
HP:0002381 Aphasia Very frequent (99-80%)
HP:0006352 Failure of eruption of permanent teeth Very frequent (99-80%)
HP:0008081 Pes valgus Very frequent (99-80%)
HP:0010529 Echolalia Very frequent (99-80%)
HP:0010743 Short metatarsal Very frequent (99-80%)
HP:0011039 Abnormality of the helix Very frequent (99-80%)
HP:0011300 Broad fingertip Very frequent (99-80%)
HP:0011833 Overhanging nasal tip Very frequent (99-80%)
HP:0011968 Feeding difficulties Very frequent (99-80%)
HP:0012471 Thick vermilion border Very frequent (99-80%)
HP:0040019 Finger clinodactyly Very frequent (99-80%)
HP:0100633 Esophagitis Very frequent (99-80%)
HP:0200055 Small hand Very frequent (99-80%)
HP:0000451 Triangular nasal tip Frequent (79-30%)
HP:0000486 Strabismus Frequent (79-30%)
HP:0001063 Acrocyanosis Frequent (79-30%)
HP:0001250 Seizures Frequent (79-30%)
HP:0001344 Absent speech Frequent (79-30%)
HP:0001786 Narrow foot Frequent (79-30%)
HP:0002066 Gait ataxia Frequent (79-30%)
HP:0002472 Small cerebral cortex Frequent (79-30%)
HP:0002793 Abnormal pattern of respiration Frequent (79-30%)
HP:0002883 Hyperventilation Frequent (79-30%)
HP:0007370 Aplasia/Hypoplasia of the corpus callosum Frequent (79-30%)
HP:0010535 Sleep apnea Frequent (79-30%)
HP:0000028 Cryptorchidism Occasional (29-5%)
HP:0000054 Micropenis Occasional (29-5%)
HP:0000718 Aggressive behavior Occasional (29-5%)
HP:0000729 Autistic behavior Occasional (29-5%)
HP:0001053 Hypopigmented skin patches Occasional (29-5%)
HP:0002558 Supernumerary nipple Occasional (29-5%)
HP:0002650 Scoliosis Occasional (29-5%)
HP:0008897 Postnatal growth retardation Occasional (29-5%)
HP:0040082 Happy demeanor Occasional (29-5%)
HP:0100716 Self-injurious behavior Occasional (29-5%)
HP:0002251 Aganglionic megacolon Very rare (4-1%)
HP:0012189 Hodgkin lymphoma Very rare (4-1%)


Phenotype(s) retrieved from case reports

    Total: 14

HPO ID Term # of case reports
HP:0002883 Hyperventilation 5
HP:0000154 Wide mouth 2
HP:0000252 Microcephaly 1
HP:0000490 Deeply set eye 1
HP:0000687 Widely spaced teeth 1
HP:0001249 Intellectual disability 1
HP:0001250 Seizures 1
HP:0001298 Encephalopathy 1
HP:0002104 Apnea 1
HP:0004879 Intermittent hyperventilation 1
HP:0011947 Respiratory tract infection 1
HP:0012450 Chronic constipation 1
HP:0025356 Psychomotor retardation 1
HP:0200134 Epileptic encephalopathy 1


Causative gene(s) retrieved from Orphanet

    Total: 2

Gene Symbol Gene Name Entrez Gene ID
TCF4 transcription factor 4 6925
TCF4 transcription factor 4 6925