Pitt-Hopkins syndrome

Información en español Title

Other Names:

Pitt Hopkins syndrome; Intellectual disability, wide mouth, distinctive facial features, and intermittent hyperventilation followed by apnea

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

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.^[1]^[2]

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.^[1]

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.^[1]

Last updated: 6/11/2018

Symptoms Symptoms

Pitt-Hopkins syndrome (PTHS) can have a variety of signs and symptoms. Specific symptoms present and their severity can vary from person to person. Early symptoms, which often become apparent in the first year of life, may include very low muscle tone (hypotonia) and significant developmental delays. Some infants have a small head size (microcephaly). Children may learn to walk months or years later than expected, and some children never acquire the skills to walk independently. Speech is significantly delayed, and while some children learn to say a few words, most do not speak. However, some are able to understand and follow simple directions. Intellectual disability generally ranges from moderate to severe.^[1]^[2]^[3]

Additional signs and symptoms of PTHS may include:^[1]^[2]^[3]^[4]

Behavioral differences: Symptoms of autism spectrum disorder may be present. Other behavioral characteristics that have been reported include unusual behavior during feeding, aggressive outbursts, anxiety, hand biting and head banging, and other stereotypic hand or head movements. However, many children with PTHS are described as having happy dispositions.
Distinctive facial features: These may become more obvious with age and may include deeply-set eyes, a prominent nose, short philtrum, wide mouth, full lower lip, widely-spaced teeth, and/or a prominent chin.
Breathing problems: These may include episodes of rapid breathing (episodic hyperventilation) followed by episodes of struggling to breath or not breathing. Episodes of breathing problems may be triggered by anxiety, excitement, or tiredness. Failure to breathe may cause a bluish discoloration of the skin (cyanosis) or fainting.
Seizures: These occur in almost half of people with PTHS, and the type and severity varies. Seizures may begin any time during childhood or adolescence.
Sleep disturbances: These may include problems falling asleep or staying asleep, and/or night terrors.
Eye or vision problems: Nearsightedness (myopia) can be severe and may become apparent before 2 years of age. Other eye abnormalities may include misalignment (strabismus) and astigmatism.
Gastrointestinal problems: These may include early feeding issues (which often resolve), constipation (which can be severe), and reflux.
Skeletal features: Those that have been reported in people with PTHS include scoliosis, flat feet, clubfoot, small hands and feet, broad fingertips or tapered fingers, bent or curved finger (clinodactyly), and overlapping toes.

More detailed information about signs and symptoms that may occur in people with PTHS is available from the National Organization for Rare Disorders (NORD) and GeneReviews.

Last updated: 6/11/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Abnormal palate morphology	Abnormality of the palate Abnormality of the roof of the mouth [ more ]	0000174
Anteverted nares	Nasal tip, upturned Upturned nasal tip Upturned nose Upturned nostrils [ more ]	0000463
Aphasia	Difficulty finding words Losing words Loss of words [ more ]	0002381
Astigmatism	Abnormal curving of the cornea or lens of the eye	0000483
Broad fingertip	Broad fingertips	0011300
Coarse facial features	Coarse facial appearance	0000280
Constipation		0002019
Deeply set eye	Deep set eye Deep-set eyes Sunken eye [ more ]	0000490
Dysphasia		0002357
Echolalia	Echoing another person's speech	0010529
Esophagitis	Inflammation of the esophagus	0100633
Failure of eruption of permanent teeth		0006352
Failure to thrive	Faltering weight Weight faltering [ more ]	0001508
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Finger clinodactyly		0040019
Full cheeks	Apple cheeks Big cheeks Increased size of cheeks Large cheeks [ more ]	0000293
Gastroesophageal reflux	Acid reflux Acid reflux disease Heartburn [ more ]	0002020
Global developmental delay		0001263
Hiatus hernia	Stomach hernia	0002036
Intellectual disability, moderate	IQ between 34 and 49	0002342
Microcephaly	Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ]	0000252
Misalignment of teeth	Abnormal dental position Abnormal teeth spacing Abnormality of alignment of teeth Abnormality of teeth spacing Crooked teeth Malaligned teeth Malposition of teeth Malpositioned teeth [ more ]	0000692
Muscular hypotonia	Low or weak muscle tone	0001252
Mutism	Inability to speak Muteness [ more ]	0002300
Myopia	Close sighted Near sighted Near sightedness Nearsightedness [ more ]	0000545
Narrow forehead	Decreased width of the forehead	0000341
Overhanging nasal tip	Drooping nasal tip Hooked tip of nose Low hanging nasal tip Nasal tip, overhanging [ more ]	0011833
Pes planus	Flat feet Flat foot [ more ]	0001763
Pes valgus		0008081
Prominent nasal bridge	Elevated nasal bridge High nasal bridge Prominent bridge of nose Prominent nasal root Protruding bridge of nose Protruding nasal bridge [ more ]	0000426
Short metatarsal	Short long bone of foot	0010743
Short neck	Decreased length of neck	0000470
Short philtrum		0000322
Single transverse palmar crease		0000954
Small hand	Disproportionately small hands	0200055
Specific learning disability		0001328
Tapered finger	Tapered fingertips Tapering fingers [ more ]	0001182
Thick vermilion border	Full lips Increased volume of lip Plump lips Prominent lips Thick lips [ more ]	0012471
Thickened helices		0000391
Upslanted palpebral fissure	Upward slanting of the opening between the eyelids	0000582
Wide mouth	Broad mouth Large mouth [ more ]	0000154
30%-79% of people have these symptoms
Absent speech	Absent speech development Lack of language development Lack of speech No speech development No speech or language development Nonverbal [ more ]	0001344
Acrocyanosis	Persistent blue color of hands, feet, or parts of face	0001063
Aplasia/Hypoplasia of the corpus callosum		0007370
Gait ataxia	Inability to coordinate movements when walking	0002066
Hyperventilation	Rapid breathing	0002883
Narrow foot	Slender feet	0001786
Seizures	Seizure	0001250
Sleep apnea	Pauses in breathing while sleeping	0010535
Small cerebral cortex		0002472
Strabismus	Cross-eyed Squint Squint eyes [ more ]	0000486
Triangular nasal tip	Triangular shaped tip of nose	0000451
5%-29% of people have these symptoms
Aggressive behavior	Aggression Aggressive behaviour Aggressiveness [ more ]	0000718
Autistic behavior		0000729
Cryptorchidism	Undescended testes Undescended testis [ more ]	0000028
Happy demeanor		0040082
Hypopigmented skin patches	Patchy loss of skin color	0001053
Micropenis	Short penis Small penis [ more ]	0000054
Postnatal growth retardation	Growth delay as children	0008897
Scoliosis	Abnormal curving of the spine	0002650
Self-injurious behavior	Self-injurious behaviour	0100716
Supernumerary nipple	Accessory nipple	0002558
1%-4% of people have these symptoms
Aganglionic megacolon	Enlarged colon lacking nerve cells	0002251
Hodgkin lymphoma		0012189
Percent of people who have these symptoms is not available through HPO
Abnormal autonomic nervous system physiology		0012332
Autosomal dominant inheritance		0000006
Clinodactyly	Permanent curving of the finger	0030084
Clubbing	Clubbing of fingers and toes	0001217
Cupped ear	Cup-shaped ears Simple, cup-shaped ears [ more ]	0000378
Encephalopathy		0001298
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Hypoplasia of the corpus callosum	Underdevelopment of part of brain called corpus callosum	0002079
Incoordination	Difficulties in coordination Incoordination of limb movements Limb incoordination [ more ]	0002311
Intellectual disability, progressive	Mental retardation, progressive Progressive mental retardation [ more ]	0006887
Intellectual disability, severe	Early and severe mental retardation Mental retardation, severe Severe mental retardation [ more ]	0010864
Intermittent hyperventilation	Intermittent overbreathing	0004879
Motor delay		0001270
Open mouth	Gaped jawed appearance Gaped mouthed appearance Slack jawed appearance [ more ]	0000194
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431
Widely spaced teeth	Wide-spaced teeth Widely-spaced teeth [ more ]	0000687

Showing of 80 |

Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 10/1/2019

Do you have updated information on this disease? We want to hear from you.

Diagnosis Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

There is no cure for Pitt-Hopkins syndrome (PTHS), but there are ways to manage or improve signs and symptoms. Treatment depends on the specific symptoms and severity in each person and ideally is managed by a team of specialists with knowledge of PTHS. Treatment may involve:^[1]^[3]

Early intervention services for infants and young children, which may include occupational, physical, speech and feeding therapies.
An individualized education plan (IEP) for preschool and school-aged children.
Behavioral therapies - children may benefit from treatments for autism spectrum disorder (such as applied behavioral analysis, or ABA) or medications.
Consideration of medication for significant breathing problems. Some individuals with PTHS have reported improvement of breathing problems with antiepileptic drugs or acetazolamide.
Routine treatment of seizures, nearsightedness, constipation, and orthopedic problems.
The use of durable medical equipment (such as wheelchairs, walkers, and adaptive strollers) as needed.

Children with PTHS should continue to have developmental assessments as their needs change with age. Regular appointments with an ophthalmologist are recommended to monitor and manage vision changes and other eye conditions. Periodic evaluations with a genetics professional are also recommended, as new information about the course of PTHS and treatment options may become available.^[1]

Last updated: 6/12/2018

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.
The Pitt Hopkins Research Foundation provides information about Pitt Hopkins clinics that specialize in the evaluation and treatment of people with Pitt Hopkins syndrome. They currently provide information about clinics at Children’s Health, University of Texas Southwestern, University of California San Francisco, and Massachusetts General Hospital.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The principal differential diagnosis includes Angelman syndrome, Rett syndrome and Mowat-Wilson syndrome (see these terms). Visit the Orphanet disease page for more information.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

The Pitt Hopkins Research Foundation provides information about how to get involved in research to help create a better understanding of Pitt Hopkins Syndrome for research, diagnosis and symptomatic treatment options.

Patient Registry

A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Pitt-Hopkins syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

Registries for Pitt-Hopkins syndrome:
Pitt Hopkins Research Foundation Family Registry

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Child Neurology Foundation
201 Chicago Avenue #200
Minneapolis, MN 55415
Telephone: 952-846-7942
Website: http://www.childneurologyfoundation.org
Epilepsy Foundation
8301 Professional Place East
Suite 230
Landover, MD 20785
Toll-free: 800-332-1000 (24/7 Helpline)
Telephone: +1-301-459-3700
Fax: +1-301-577-2684
E-mail: contactus@efa.org
Website: https://www.epilepsy.com/
en Español 1-866-748-8008
Pitt Hopkins Research Foundation
E-mail: phrf@pitthopkins.org
Website: http://pitthopkins.org/
Pitt Hopkins UK
E-mail: http://pitthopkins.org.uk/?page_id=206
Website: http://pitthopkins.org.uk/

Social Networking Websites

RareConnect has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

Pitt Hopkins Syndrome Support Group
E-mail: pitt-hopkins@googlegroups.com
Website: http://groups.google.com/group/pitt-hopkins

Do you know of an organization? We want to hear from you.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Pitt-Hopkins syndrome. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
The Pitt Hopkins Research Foundation provides information about Pitt-Hopkins syndrome.

In-Depth Information

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Pitt-Hopkins syndrome. Click on the link to view a sample search on this topic.

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What is the prognosis for Pitt-Hopkins syndrome? See answer

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References References

Sweetser DA, Elsharkawi I, Yonker L, Steeves M, Parkin K, Thibert R. Pitt-Hopkins Syndrome. GeneReviews. April 12, 2018; http://www.ncbi.nlm.nih.gov/books/NBK100240/.
Pitt-Hopkins syndrome. Genetics Home Reference (GHR). February, 2015; http://ghr.nlm.nih.gov/condition/pitt-hopkins-syndrome.
Pitt-Hopkins Syndrome. National Organization for Rare Disorders (NORD). 2018; https://rarediseases.org/rare-diseases/pitt-hopkins-syndrome/.
de Winter CF, Baas M, Bijlsma EK, van Heukelingen J, Routledge S, Hennekam RCM. Phenotype and natural history in 101 individuals with Pitt-Hopkins syndrome through an internet questionnaire system. Orphanet Journal of Rare Diseases. 2016; 11:37:https://ojrd.biomedcentral.com/articles/10.1186/s13023-016-0422-2.