FAQ

Both these questions are very difficult to answer as there are so few cases in the world to be able to make an accurate estimate. At present, it is thought that there are only a few thousand cases diagnosed in the world but many undiagnosed or misdiagnosed. Based on the experience from other rare diseases it is possible that the prevalence of PTHS in the population is 1 in 225,000 – 300,000 or roughly 4 in a million. The population of the UK is about 65 million so the incidence of PTHS in the UK should be about 260 cases. It was estimated that about 200 cases of PTHS were diagnosed in the UK  in July 2014 and the estimate has risen to about 300. Pitt Hopkins UK was in contact with about 60 families in Feb 2016 and approaching 100 in 2020 and so possibly with about a third of the families.  

You will see other numbers on the internet so some explanation is needed for these figures. Sometimes numbers are given by an approximation of names known. This may be needed for grants etc. We can then say for sure that there are hundreds of people diagnosed as we can get this information from numbers on the international support groups.

In the UK we have a different situation as testing is done through the National Health Service. Our genetic centres are able to confer more easily than in some other parts of the world. In 2014 most regional genetic centres had diagnosed about 7 to 8 cases and from this, it was estimated there were at least 200 cases in the UK at that time. As said above we are in contact with 62 families. It should be understood that not every family makes contact with a support group or organisation or even know they exist, especially if they may have been told by their doctor they don’t know of any support group in the UK.

The numbers known in The Netherlands were around 50 in 2014 and as the population is a quarter of that in the UK the number of 200 in 2014 in the UK matched quite well. Using the recognition of a syndrome in one, smaller country, to calculate the frequency in other countries is a legitimate approach.

We cannot name a few thousand around the world but in the UK we could name 90-100 which is about a third of the number thought to be diagnosed. (Obviously for privacy reasons we won’t )

Of course, there are many who have PTHS in the UK, probably adults, that are not diagnosed at all or possibly misdiagnosed!

As far as is known to date, children with PTHS appear to have a normal life expectancy. However, seizures arising from epilepsy have their own inherent complications and this could affect life expectancy as with anyone else.

Many children with Pitt-Hopkins syndrome will not learn to talk or will have a vocabulary of just a few words but they will be able to understand far more than they can express. It can be very frustrating to them to have a larger receptive than expressive vocabulary and this can lead to some behavioural problems so input from a specialist speech and language therapist is extremely important.

Most children with PTHS have hypotonia. This means they have low muscle tone and leads to delayed motor development. Most will learn to roll, sit, crawl and walk much later than other children. A few children will not manage to walk. All children with PTHS will need the input of a specialist paediatric physiotherapist. Some children will not have as many problems with motor development as others. Some may walk as early as 18 months 2 years old but most will walk around 6 years of age. They may have slow coordination of their limbs which can cause a stiff gait when they walk.

The main symptoms of the condition are severe learning disability, breathing abnormalities with intermittent periods of over breathing and daytime apnoea and characteristic facial features including a wide mouth, prominent lips and deep-set eyes. Individuals with Pitt-Hopkins syndrome are often short compared to other family members and have a small head size. Seizures may be present and brain scans often show specific abnormalities including agenesis of the corpus callosum. There are minor differences in the shape of the fingers and slim feet, often with shortening of the little toes. Constipation may be a problem. Speech is very limited in Pitt-Hopkins syndrome, often to a few words. It has been noted that many people with Pitt-Hopkins syndrome have a tendency to smile frequently and this characteristic, together with some unsteadiness on walking leads to the diagnosis often being confused with Angelman Syndrome. The breathing abnormalities, sometimes associated with colour change, are not present in every person and may not appear until mid-childhood. This diagnosis is therefore often made relatively late.

(the above answer is taken with kind permission from the Contact a Family website and from Prof Jill Clayton-Smith, Consultant Clinical Geneticist, St Mary’s Hospital Manchester
Medical text written January 2009)

Pitt-Hopkins syndrome is now most frequently referred to as PTHS. It is formed by taking the first and last letters of Pitt and the first letter of Hopkins , who were the two doctors who characterised the syndrome in 1978, together with the S for syndrome. This is to distinguish it from another rare syndrome known as Pallister-Hall syndrome which was already known as PHS in the science and medical literature. It is still referred to as PHS in some medical literature.