Kisho

Kisho is an information platform, not a medical provider. Nothing on this site constitutes medical advice, diagnosis, or treatment recommendations. All content is aggregated from publicly available sources (including ClinicalTrials.gov, PubMed, FDA.gov, and Orphanet) and is provided for informational purposes only. Clinical trial eligibility, treatment decisions, and any health-related actions should always be discussed with a qualified healthcare professional. Kisho does not endorse any specific therapy, organization, or clinical trial. Terms of use · Privacy policy

Pitt-Hopkins syndrome (PTHS) - Clinical Profile, Genes & Research | Kisho | Kisho

Features include always present findings: Sparse medial eyebrow, Widely spaced teeth, Deep philtrum, and Severe intellectual disability and others; and very common findings: Astigmatism, Low muscle tone (hypotonia), Gastroesophageal reflux, and Coarse facial features and others. 96 total HPO annotations.

Organ System	Phenotype Count	Example Features
Brain and nerves	16	Seizure, Gait ataxia, Intellectual disability
Arms and legs	7	Prominent fingertip pads, Overlapping toe, Tapered finger
Digestive system	4	Gastroesophageal reflux, Constipation, Feeding difficulties
Head and neck	4	Coarse facial features, Microcephaly, Secondary microcephaly
Growth and development	3	Failure to thrive, Growth delay, Postnatal growth retardation
Skin	2	Hyperconvex nail, Hypopigmented skin patches
Eyes	1	Strabismus
Muscles	1	Low muscle tone (hypotonia)
Bones and joints	1	Sideways curvature of the spine (scoliosis)
Pregnancy and birth	1	Fetal nuchal edema
Lungs and breathing	1	Sleep apnea
Blood and immune system	1	Hodgkin lymphoma

GeneReviews

Clinical Guidance

Pitt-Hopkins syndrome (PTHS) is characterized by distinctive facial features, significant developmental delays with moderate-to-severe intellectual disability, neurobehavioral/psychiatric manifestations (e.g., stereotypic hand movements, autism spectrum disorder), and autonomic dysfunction (e.g., episodic hyperventilation and/or breath-holding while awake). Speech is significantly affected. Although most individuals are nonverbal, receptive language is often stronger than expressive language. Other common findings are sleep disturbances, seizures, constipation, and severe myopia .

Table 2.

Pitt-Hopkins Syndrome: Frequency of Select Features

Feature | % of Persons w/Feature

Facial gestalt | 90%-95%

Developmental delay/ intellectual disability | 100%

Delayed motor milestones | 100%

Source: GeneReviews — "Pitt-Hopkins Syndrome"

Diagnosis

Drawn from GeneReviews diagnostic guidelines, newborn screening panel status (RUSP), and ClinGen gene-disease validity classifications. Reflects current clinical evidence and consensus where available.

GeneReviews

Diagnostic Criteria

Clinical and molecular diagnostic criteria for Pitt-Hopkins syndrome (PTHS) have been established [.]

Suggestive Findings

PTHS should be suspected in a proband with the following clinical and imaging findings and family history.

Clinical findings

• Developmental delay/ intellectual disability

Delayed motor milestones, often associated with hypotonia
Severely limited-to-absent speech, with regression in verbal abilities in some individuals
Intellectual disability, typically moderate to severe

• Neurobehavioral/psychiatric manifestations

Source: GeneReviews — "Pitt-Hopkins Syndrome"

GeneReviews

Differential Diagnosis

Disorders with features that overlap those of Pitt-Hopkins syndrome (PTHS) are listed in . Of these disorders, Rett syndrome and Angelman syndrome are the most common. Most of the disorders are distinguished from PTHS by the absence of typical PTHS facial features. Table 3. Disorders to Consider in the Differential Diagnosis of Pitt-Hopkins Syndrome

Gene(s)/ Genetic Alteration	Disorder	MOI	Common Features of Disorder
ARX	ARX-related ID syndrome (OMIM 309510)	XL	DD, severe speech disorder, seizures; Recurrent hyperventilation episodes reported in 1 persons w/an ARX pathogenic variant.

Genetic testing for TCF4 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for Pitt-Hopkins syndrome has been reported in the published literature.

Treatment

Compiled from FDA-approved drug records, orphan drug designations, and FDA Adverse Event Reporting System (FAERS) safety data. GeneReviews management guidance is included where available.

No approved treatments are currently available for Pitt-Hopkins syndrome. An additional 3 compounds hold orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for Pitt-Hopkins syndrome, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for Pitt-Hopkins syndrome. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Brand Name	Generic Name	Sponsor	Designated	Exclusivity End	Designation Status
Lyophilized microbiota purified from the stool of screened, healthy human donors	Lyophilized microbiota purified from the stool of screened, healthy human donors	Gut-Brain Axis Therapeutics	2023	—	Designated
nicardipine	nicardipine	Collaborations Pharmaceuticals, Inc.	2019	—	Designated
Cyclo(-L-Glycyl-L-2-Allylproline)	Cyclo(-L-Glycyl-L-2-Allylproline)	Neuren Pharmaceuticals, Ltd.	2019	—	Designated

Gene therapy approaches for Pitt-Hopkins syndrome have been reported in the published literature.

GeneReviews

Management Guidelines

Clinical practice guidelines for management of individuals with Pitt-Hopkins syndrome (PTHS) have been published .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with PTHS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 4.

Pitt-Hopkins Syndrome: Recommended Evaluations Following Initial Diagnosis

System/Concern | Evaluation | Comment

Neurologic eval

| By child neurologist | • To establish a neurologic baseline evaluate for other neurologic issues such as sleep dysfunction or seizures

To incl brain MRI if not previously performed
Consider EEG if seizures are a concern.

Developmental delay/ intellectual disability

| Developmental assessment | • To assess cognitive baseline determine the types of services educational strategies needed

For infants young children: evaluate for early intervention.
For school-age children: determine need for IEP or 504 plan.

Communication skills

Clinical Trials

5 trials found

Explore Trials

Prognosis

Based on GeneReviews surveillance recommendations, HPO phenotype frequency and severity annotations, and published prevalence estimates from Orphanet and OMIM.

GeneReviews

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. Pitt-Hopkins Syndrome: Recommended Surveillance

System/Concern	Evaluation	Frequency
Development	Monitor developmental progress educational needs.	At each visit Feeding
Ophthalmologic	Monitor for changes in refractive error (usually high myopia) strabismus.	Per treating ophthalmologist Low vision services
Musculoskeletal	Physical medicine specialist OT/PT to assess mobility, need for orthotics, durable equipment, self-help skills	At each visit Assess for scoliosis.
Family/Community	Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).	At each visit
Transition to adult care	Develop plan for transition from pediatric to adult care.2	Starting by age ~10 yrs ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; OT = occupational therapist; PT = physical therapist 1.

Source: GeneReviews — "Pitt-Hopkins Syndrome"

Phenotype severity distribution: 7 always present features, 46 very common features, 16 common features.

Estimated prevalence: Unknown (Unknown prevalence).

Research Landscape

Sourced from ClinicalTrials.gov and PubMed. Publication types are classified using NLM-curated article metadata; research type breakdowns reflect the nature of published work for this disease.

5 clinical trials registered, 1 recruiting. Interventions under study include other interventions, drug therapy, and gene therapy. Pipeline includes 1 PHASE2, 2 PHASE1. Research is sponsored by a mix of industry and academic institutions.

NCT ID	Title	Phase	Sponsor	Status
[NCT06321796](https://clinicaltrials.gov/study/NCT06321796)	Microbiota Transfer Therapy for Children and Adults With Both Pitt Hopkins Syndrome and Gastrointestinal Disorders	PHASE2	Gut-Brain-Axis Therapeutics Inc.	UNKNOWN
[NCT07135050](https://clinicaltrials.gov/study/NCT07135050)	Phase 1/2 Study of MZ-1866, an AAV-9 Gene Therapy Delivered by Intracerebroventricular Injection to Participants With Pitt Hopkins Syndrome	PHASE1	Mahzi Therapeutics	UNKNOWN
[NCT03655223](https://clinicaltrials.gov/study/NCT03655223)	Early Check: Expanded Screening in Newborns	—	RTI International	ACTIVE_NOT_RECRUITING
[NCT07150026](https://clinicaltrials.gov/study/NCT07150026)	An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Pitt Hopkins Syndrome	PHASE1	Unravel Biosciences, Inc.	UNKNOWN
[NCT01793168](https://clinicaltrials.gov/study/NCT01793168)	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford	—	Sanford Health	RECRUITING

37 publications have been identified in PubMed for Pitt-Hopkins syndrome. Research spans Basic Science / Preclinical (51%), Case Report / Case Series (27%), and Epidemiology / Natural History (8%).

Research Type	Count	% of Total
Laboratory research	19	51%
Patient case studies	10	27%
Disease patterns and progression	3	8%
Testing and diagnosis research	2	5%
New treatment approaches	2	5%
Research summaries	1

Recent Publications

Shen W (2026). [PMID: 42210665](https://pubmed.ncbi.nlm.nih.gov/42210665/). *Mol Genet Genomic Med*. [Case Report / Case Series]
Burette AC (2026). [PMID: 42238855](https://pubmed.ncbi.nlm.nih.gov/42238855/). *Front Neuroanat*. [Basic Science / Preclinical]
Tamberg L (2026). [PMID: 41500834](https://pubmed.ncbi.nlm.nih.gov/41500834/). *eNeuro*. [Basic Science / Preclinical]
Vermudez SAD (2026). [PMID: 41997465](https://pubmed.ncbi.nlm.nih.gov/41997465/). *Mol Cell Neurosci*. [Basic Science / Preclinical]
Sozańska N (2026). [PMID: 42106138](https://pubmed.ncbi.nlm.nih.gov/42106138/). *Arch Biochem Biophys*. [Basic Science / Preclinical]
de Carvalho LM (2025). [PMID: 39929970](https://pubmed.ncbi.nlm.nih.gov/39929970/). *Scientific reports*. [Basic Science / Preclinical]
Sozańska N (2025). [PMID: 40452023](https://pubmed.ncbi.nlm.nih.gov/40452023/). *Cell communication and signaling : CCS*. [Basic Science / Preclinical]
Arnold ZE (2025). [PMID: 40822316](https://pubmed.ncbi.nlm.nih.gov/40822316/). *Translational science of rare diseases*. [Case Report / Case Series]
Zeng L (2025). [PMID: 41253748](https://pubmed.ncbi.nlm.nih.gov/41253748/). *Translational psychiatry*. [Basic Science / Preclinical]
Suspitsin EN (2025). [PMID: 41255692](https://pubmed.ncbi.nlm.nih.gov/41255692/). *World journal of clinical pediatrics*. [Epidemiology / Natural History]

Kisho

Pitt-Hopkins syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Orphan Drug Designations

Management Guidelines

Evaluations Following Initial Diagnosis

Neurologic eval

Developmental delay/ intellectual disability

Communication skills

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Questions for Your Care Team

Questions for Your Care Team

Behavioral abnormalities

Breathing abnormalities

Pitt-Hopkins syndrome

Overview

Clinical Presentation

Clinical Guidance

Explore clinical features

Genetic Landscape

Diagnosis

Diagnostic Criteria

Suggestive Findings

Differential Diagnosis

Treatment

Orphan Drug Designations

Management Guidelines

Evaluations Following Initial Diagnosis

Neurologic eval

Developmental delay/ intellectual disability

Communication skills

Clinical Trials

Prognosis

Surveillance Guidelines

Research Landscape

Recent Publications

Medical References

External Resources

OMIM

Orphanet

GARD

Related Diseases

Questions for Your Care Team

Questions for Your Care Team

Behavioral abnormalities

Breathing abnormalities