Pitt-Hopkins syndrome

A developmental disorder characterized by intellectual disability, wide mouth and distinctive facies, and intermittent hyperventilation followed by APNEA. It is caused by de novo autosomal dominant mutations in the TCF4 gene. OMIM: 610954

Also Known As:

Networked: 52 relevant articles (2 outcomes, 1 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neurodevelopmental Disorders
2.	Schizophrenia (Dementia Praecox)
3.	Intellectual Disability (Idiocy)
4.	Autism Spectrum Disorder
5.	Autistic Disorder (Autism)

Experts

1.	Sepp, Mari: 7 articles (12/2021 - 07/2012)
2.	Timmusk, Tõnis: 6 articles (12/2021 - 07/2012)
3.	Maher, Brady J: 5 articles (01/2021 - 01/2016)
4.	Kennedy, Andrew J: 3 articles (10/2022 - 10/2015)
5.	Nurm, Kaja: 3 articles (12/2021 - 10/2017)
6.	Page, Stephanie Cerceo: 3 articles (10/2017 - 01/2016)
7.	Rannals, Matthew D: 3 articles (03/2017 - 01/2016)
8.	Sweatt, J David: 3 articles (01/2016 - 05/2013)
9.	Philpot, Benjamin D: 2 articles (10/2022 - 01/2018)
10.	Vihma, Hanna: 2 articles (10/2022 - 10/2017)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Pitt-Hopkins syndrome:

1.	Acetazolamide (Diamox)FDA LinkGeneric 06/01/2015 - "Successful use of acetazolamide for central apnea in a child with Pitt-Hopkins syndrome." 04/01/2012 - "Acetazolamide for severe apnea in Pitt-Hopkins syndrome." 01/01/2022 - "We present a case of a teenage patient with Pitt-Hopkins syndrome who had very frequent apneic spells that responded well to treatment with topiramate after limited response to acetazolamide."
2.	Topiramate (Topamax)FDA LinkGeneric 01/01/2022 - "A Case Report of Topiramate for Severe Breath Holding Spells in a Teenage Boy with Pitt-Hopkins Syndrome." 01/01/2022 - "We present a case of a teenage patient with Pitt-Hopkins syndrome who had very frequent apneic spells that responded well to treatment with topiramate after limited response to acetazolamide."
3.	Clemastine (Clemastine Fumarate)FDA LinkGeneric 01/01/2023 - "In this study, we show that the promyelinating compounds, clemastine, sobetirome and Sob-AM2 are effective at restoring myelination defects in a Pitt-Hopkins syndrome mouse model. "
4.	GC 1 compoundIBA 01/01/2023 - "In this study, we show that the promyelinating compounds, clemastine, sobetirome and Sob-AM2 are effective at restoring myelination defects in a Pitt-Hopkins syndrome mouse model. " 01/01/2023 - "To confirm behavioural rescue was achieved via enhancing myelination, we show that treatment with the thyroid hormone receptor agonist sobetirome or its brain penetrating prodrug Sob-AM2, was also effective at normalizing oligodendrocyte precursor cell and oligodendrocyte densities and behaviour in the Pitt-Hopkins syndrome mouse model. "
5.	Transcription Factor 4IBA 01/20/2023 - "Genetic variation in the transcription factor 4 ( TCF4) gene is associated with risk for a variety of developmental and psychiatric conditions, which includes a syndromic form of ASD called Pitt Hopkins Syndrome (PTHS). " 01/01/2021 - "Molecular and Cellular Function of Transcription Factor 4 in Pitt-Hopkins Syndrome." 12/01/2020 - "Pitt-Hopkins syndrome is a rare neurodevelopment disorder caused by haploinsufficiency of the transcription factor 4 (TCF4). " 03/01/2017 - "Molecular Mechanisms of Transcription Factor 4 in Pitt Hopkins Syndrome." 04/12/2016 - "Pitt-Hopkins syndrome (PTHS; MIM# 610954) is a genetically determined entity mainly caused by mutations in TransCription Factor 4 (TCF4). "
6.	Basic Helix-Loop-Helix Transcription FactorsIBA 06/01/2016 - "Mutations in TCF4 (basic helix-loop-helix transcription factor 4), a gene with complex organization and multiple transcription initiation sites, are usually associated with Pitt-Hopkins syndrome (PTHS). " 01/01/2016 - "Mutations of TCF4, which encodes a basic helix-loop-helix transcription factor, cause Pitt-Hopkins syndrome (PTHS) via multiple genetic mechanisms. " 01/01/2020 - "Germline mutations in the basic helix-loop-helix transcription factor 4 (TCF4) cause the Pitt-Hopkins syndrome (PTHS), a developmental disorder with severe intellectual disability. " 06/15/2007 - "Severe mental retardation with breathing abnormalities (Pitt-Hopkins syndrome) is caused by haploinsufficiency of the neuronal bHLH transcription factor TCF4." 05/01/2007 - "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."
7.	Proteins (Proteins, Gene)FDA Link 01/01/2016 - "Finally, moderate reduction of ribosome content and general protein synthesis followed overexpression of two Pitt-Hopkins syndrome mutant variants of TCF4. " 05/01/2017 - "Intragenic deletions of the contactin-associated protein-like 2 gene (CNTNAP2) have been found in patients with Gilles de la Tourette syndrome, intellectual disability (ID), obsessive compulsive disorder, cortical dysplasia-focal epilepsy syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, stuttering, and attention deficit hyperactivity disorder. " 02/01/2015 - "Based on genomic rearrangements and copy number variations, the contactin-associated protein-like 2 gene (CNTNAP2) has been implicated in neurodevelopmental disorders such as Gilles de la Tourette syndrome, intellectual disability, obsessive compulsive disorder, cortical dysplasia-focal epilepsy syndrome, autism, schizophrenia, Pitt-Hopkins syndrome, and attention deficit hyperactivity disorder. " 12/01/2022 - "TCF4 haploinsufficiency by deletions, truncating variants or loss-of-function missense variants within the DNA-binding and protein interacting bHLH domain causes Pitt-Hopkins syndrome (PTHS). " 12/01/2021 - "We show that Pitt-Hopkins syndrome-associated missense mutations within the basic helix-loop-helix domain of TCF4 and a Rett-like syndrome-associated mutation in a transcription activation domain result in altered DNA-binding and transcriptional activity of the protein. "
8.	Valproic Acid (Depakote)FDA LinkGeneric 12/01/2012 - "Clinical and polygraphic improvement of breathing abnormalities after valproate in a case of Pitt-Hopkins syndrome." 10/01/2019 - "A 13-year-old girl with genetically confirmed Pitt-Hopkins syndrome with uncontrolled seizures, while on treatment with levetiracetam and valproic acid, was started on perampanel, reaching seizure control. "
9.	Transcription Factors (Transcription Factor)IBA 07/01/2012 - "Pitt-Hopkins syndrome-associated mutations in TCF4 lead to variable impairment of the transcription factor function ranging from hypomorphic to dominant-negative effects." 05/03/2013 - "TCF4 (transcription factor 4; E2-2, ITF2) is a transcription factor that when haplo-insufficient causes Pitt-Hopkins Syndrome (PTHS), an autism-spectrum disorder that is associated with pervasive developmental delay and severe intellectual disability. "
10.	DNA (Deoxyribonucleic Acid)IBA 12/01/2022 - "TCF4 haploinsufficiency by deletions, truncating variants or loss-of-function missense variants within the DNA-binding and protein interacting bHLH domain causes Pitt-Hopkins syndrome (PTHS). " 12/01/2021 - "We show that Pitt-Hopkins syndrome-associated missense mutations within the basic helix-loop-helix domain of TCF4 and a Rett-like syndrome-associated mutation in a transcription activation domain result in altered DNA-binding and transcriptional activity of the protein. "

Therapies and Procedures

1.	Therapeutics 01/01/2023 - "Together, these results provide preclinical evidence that promyelinating therapies may be beneficial in Pitt-Hopkins syndrome and potentially other neurodevelopmental disorders characterized by dysmyelination."
2.	Osteopathic Manipulation 01/01/2017 - "Osteopathic Manipulative Treatment Limits Chronic Constipation in a Child with Pitt-Hopkins Syndrome."