Pitt-Hopkins Syndrome

Pitt-Hopkins syndrome is an extremely rare genetic disease that cannot be cured. The genetic defect results in motor and mental disabilities, among other things.

Pitt-Hopkins Syndrome

What is Pitt Hopkins Syndrome?

Pitt -Hopkins syndrome (PHS) is a genetic disease associated with intellectual disability, insufficient or complete absence of spoken language, epilepsy and respiratory disorders. In addition, there are typical facial abnormalities. See dictionaryforall for PCO Syndrome in Dictionary.

The disease is very rare. So far, only 150 cases are known around the world, which occur equally in males and females. However, doctors suspect a higher number of unreported cases because the disease has only been able to be diagnosed with certainty for a few years. The name Pitt-Hopkins syndrome goes back to the two Australian physicians D. Pitt and I. Hopkins, who first described the disease in 1978.

The causative gene was not discovered until 2007. Two research groups in Erlangen and Paris found mutations in the TCF4 gene at the same time. As a result, a clear diagnosis of Pitt-Hopkins syndrome is now possible. It is estimated that the hereditary disease manifests itself in one in 34,000 to 41,000 births.


Pitt-Hopkins syndrome is inherited in an autosomal dominant manner. The hereditary disease is caused by heterozygous new mutations within the TCF4 gene. This codes for a ubiquitous b-HLH transcription factor. The TCF4 gene is located on chromosome 18. The gene either mutates on one of exons 1 to 20 or is deleted completely.

If a person suffers from Pitt-Hopkins syndrome, the risk of passing the hereditary disease on to offspring is around 50 percent. Usually, however, most patients do not have children. In most cases, the disease occurs even though both parents are healthy and do not have any mutations in the TCF4 gene. The PHS recurrence risk in further pregnancies is classified as very low at one percent.

Symptoms, Ailments & Signs

Pitt-Hopkins syndrome has a variety of different symptoms. However, these never fully manifest themselves in a patient. In most sufferers, the characteristic features of the syndrome only develop over time, so that they eventually become clearly recognizable.

Immediately after birth and in the first months of life, there are usually no significant symptoms. In the further course, the parents notice an abnormally slow development of their child. For example, he rarely grabs toys, does not turn himself, or squints. Moderate to severe mental retardation, postnatal growth retardation, impaired walking ability, impaired locomotor coordination, and hypotonia may also occur.

Bouts of hyperventilation, sleep disorders, severe constipation, scoliosis and genital abnormalities have also been reported in this condition. In addition, language development is poor or even absent. Visible facial abnormalities such as thick heart-shaped lips, a broad, flat palate with a large mouth, a macrostomia with large spaces between the teeth, and protruding teeth are also considered typical of Pitt-Hopkins syndrome.

In addition, dilated nostrils, deep-set eyes, the development of a groove between the lip and nose, the absence of a flexion of thumbs or fingers and narrow hands with wide fingertips are external identification features. Basically, however, most PHS patients have a cheerful mood, so that they often laugh. They also need a lot of love and physical contact.

Diagnosis & course of disease

Pitt-Hopkins syndrome is usually diagnosed by clinical examination. Electroencephalography (EEG), which can be used to detect changes, is also an important examination method. Imaging methods such as magnetic resonance imaging (MRT) can also be used.

These can indicate changes in the temporal lobes and a change in the hippocampus. In some cases, evidence of dilated ventricles or a hypoplastic corpus callosum (brain beam) is also possible.

If the gene mutation is already known, prenatal diagnosis can be carried out. This means that the hereditary disease can be detected before birth. Differential diagnosis also plays an important role, since the symptoms of some diseases are similar to those of Pitt-Hopkins syndrome. These include Goldberg syndrome, Angelman syndrome, Mowat-Wilson syndrome, and Rett syndrome.

Because Pitt-Hopkins syndrome is a genetic defect, it cannot be cured. In most cases, permanent mental disabilities are to be expected. In addition, most PHS patients are unable to speak. The life expectancy of those affected depends on the extent of health problems and deformities. As a rule, they need support from other people throughout their lives.


Most people affected by Pitt-Hopkins syndrome usually suffer from various motor and mental limitations and disabilities. The patients are therefore usually dependent on the help of other people in their lives and can no longer easily cope with everyday life on their own. Those affected suffer from strabismus and increased retardation.

Speech disorders and problems with coordination can also occur as a result of Pitt-Hopkins syndrome and significantly reduce the patient’s quality of life. It also causes constipation and insomnia. The entire development of the child is negatively influenced by the Pitt-Hopkins syndrome, so that there are also complications in adulthood.

The symptoms of Pitt-Hopkins syndrome can lead to teasing or bullying, especially in children. A causal treatment of Pitt-Hopkins syndrome is not possible, so those affected are dependent on various therapies that can make everyday life easier. Sometimes family members and parents also need psychological treatment. The life expectancy of the patient is usually not affected by this disease. Parents should also consider genetic counseling.

When should you go to the doctor?

Since Pitt-Hopkins syndrome is a congenital disease that does not heal itself, the syndrome must always be treated by a doctor. However, a complete cure is not possible, so that the affected person is dependent on medical treatment throughout his life.

A doctor should be consulted for Pitt-Hopkins syndrome if the child shows a significantly slower development. Squinting can also occur, with many children also having coordination disorders. A doctor should always be consulted if there are deformities or abnormalities on the face. The earlier these are recognized and treated, the higher the probability of a positive course of the disease.

Abnormalities on the child’s hands and feet can also indicate Pitt-Hopkins syndrome and must be examined by a doctor. The diagnosis of the syndrome itself can be carried out by a pediatrician or by a general practitioner. For further treatment, however, a specialist is necessary, whereby the treatment depends on the exact severity of the syndrome. Whether the disease will lead to a reduced life expectancy of the patient cannot generally be predicted. Since the syndrome often leads to psychological problems in the parents and relatives, a psychologist can also be consulted.

Treatment & Therapy

Since Pitt-Hopkins syndrome cannot be cured, therapy is limited to treating the symptoms, which in turn depends on the individual symptoms. In any case, it is important to start treating the hereditary disease as early as possible.

Physiotherapeutic measures, speech therapy, ergotherapy, riding therapy (hippotherapy) or music therapy are primarily considered as suitable forms of therapy. In the case of strabismus, occlusion therapy is important, in which one eye is taped with a special eye patch to counteract the visual disturbance.

Drug treatment with the carbonic anhydrase inhibitor acetazolamide, which is used to lower blood pressure and intracranial pressure, is also considered sensible. Some patients are also given medicines for sleep disorders, constipation, and epilepsy. A major problem with Pitt-Hopkins syndrome is a lack or absence of spoken language. For this reason, the affected children should learn to communicate through sign language. Genetic counseling is recommended for parents.

Outlook & Forecast

The prospects for a cure or improvement for hereditary Pitt-Hopkins syndrome are not particularly good. The genetically caused syndrome occurs only very rarely. More than 400 cases are undocumented worldwide.

Pitt-Hopkins Syndrome causes a whole range of severe to moderate functional disorders and mental impairments. Among other things, short stature or epilepsies develop. The children cannot speak. The problem for the parents of such children is that the correct diagnosis is usually only made after several years. It is then important to differentiate Pitt-Hopkins syndrome from other syndromes with similar symptoms.

In view of the large number of undesirable developments and consequences, medicine can only intervene symptomatically. Sufferers can often be found in the hospital because they can have serious breathing problems. The interdisciplinary treatment of those affected is standard. Given the large number of disorders, the prognosis for positive developments for those affected is not particularly good. Even surgical measures cannot change the degree of disability. Those affected require constant care.

For the parents of such children, this prognosis is a relevant factor. It is true that the chances of having another child with this disability are rather small. However, they are given. Therefore, an amniotic fluid test is recommended in the event of a further pregnancy. If necessary, an abortion must be recommended.


There are no measures to prevent Pitt-Hopkins syndrome. It is a congenital hereditary disease.


In the case of Pitt-Hopkins syndrome, follow-up care measures are significantly limited in most cases. It is a genetic disease that cannot be completely cured, so early detection and treatment of this disease is paramount to prevent further complications or other symptoms.

The sooner the syndrome is recognized and treated by a doctor, the better the further course is, as a rule. If you wish to have children, genetic testing and counseling should be carried out to prevent Pitt-Hopkins syndrome from recurring. The affected children depend on regular check-ups by various doctors throughout their lives.

The care and support of one’s own family is also very important, as this can prevent the development of depression or other mental disorders. Intensive support for the affected children is also very important at school.

Some symptoms of Pitt Hopkins syndrome are treated with medication. It is always important to ensure that the dosage is correct and that the medication is taken regularly. Pitt-Hopkins syndrome may reduce the life expectancy of those affected.

You can do that yourself

People suffering from Pitt-Hopkins syndrome are usually not able to live without help. The relatives must give the sick person the necessary support and pay attention to health problems. In addition to regular visits to the doctor, therapeutic measures such as breathing exercises and regular self-help talks are also important.

The lack of language skills can be compensated for by targeted language training. In the case of external malformations, talk therapy may also be necessary. Bed rest is required after an operation. The doctor can recommend suitable home and natural remedies for the pain and consult an alternative medicine specialist if necessary. In the event of an acute respiratory emergency, the emergency doctor must be alerted. Until medical help arrives, give first aid to the sick person and make sure they remain calm.

Pitt-Hopkins syndrome can be treated well with comprehensive care. The patients should be cared for at home by a home care service and have to attend a special kindergarten and school in later life. The associated stress burdens both the patient and the parents, who should talk to the doctor about their fears and problems. Accompanying therapy can improve well-being and open up new perspectives in life for those affected.