What is Pitt-Hopkins syndrome?
Pitt-Hopkins syndrome causes problems in the development of the nervous system, leading to abnormal brain function. People with Pitt-Hopkins look different, think differently and behave differently. These characteristic differences are caused by changes in the code that describes how a person is put together, called the DNA.
In people with Pitt-Hopkins syndrome (PTHS) the nervous system develops differently. Typically, this causes problems in thinking (intellectual disability) and problems in breathing (regulation of respiration) and digesting food (intestinal motility). Often, the faces of people with Pitt-Hopkins syndrome also look similar, with specific facial features. Pitt-Hopkins syndrome is caused by variants in "transcription factor TCF4", which is a certain part of the dna. Decisions about whether someone has this syndrome based on the way the look and act (clinical diagnostic criteria) or the way their DNA looks (molecular diagnostic criteria) differ worldwide. The way to take care of people with Pitt-Hopkins syndrome(care practices) also is not the same everywhere. To make sure everyone gets the best possible care, a group of experts from many countries decided to agree on guidelines for diagnostics and care.
For issues, for which there was limited information available in international scientific magazines and books, the experts worked together with national support groups and the participants of an international meeting about Pitt-Hopkins syndrome. Here, we discuss the things the experts agree on, including the exact way to decide whether someone has Pitt-Hopkins syndrome - which is called the clinical definition. And also the way to decide whether this can be shown in their DNA - which is called the molecular diagnostic pathway. The experts provide recommendations for managing particular health problems such as problems with breathing (dysregulated respiration). It is important that body problems and behavioral problems are treated together. To make sure that diagnostics and care keep getting better and better, the advice should be checked often and changed if necessary.
DNA, chromosomes and mutations
DNA
Every human is made up out of billions of cells. There are many different types of cells, that do many different things and look very different from one another; for instance, your skin cells on the outside look very different from the cells that make up your tongue. Cells are so small that you cannot distinguish them with your bare eyes: you can see your skin, but not an individual skin cell. Yet, each cell contains the same information about how all the cells in your body are made. This information is collected in the core of the cell, which is called the nucleus. You can envision the information, which we call DNA (short for deoxyribonucleic acid, the stuff that DNA is made from) as a cookbook, split up into chapters with recipes in them. Each human cell contains 46 chapters, called chromosomes, which have been numbered according to size. Of each size, there are two versions, so there are 23 pairs. Of every pair of chromosomes, you inherit one from your father and one from your mother. Every recipe in a chapter/chromosome contains the information to put together a tool that can do things in the body. The recipes are called genes and the tools are called proteins.
[this could be a good place for an infographic of DNA] want to help us? please contact team WaihonaPedia
Chromosomes
Every time your body makes a new cell, using the information in your DNA, a copy of all the chromosomes is made. However, sometimes mistakes are made in this process, changing the information in a gene. Chromosomes are made up out of building blocks called nucleotides. Mistakes can be either putting the wrong nucleotide in a specific spot, or leaving out nucleotides (this type of mistake is called a deletion). If the protein made on the basis of that gene still works properly, there is no problem. We all are a little different from each other, we are all unique. But when a mistake makes it impossible for the protein to work correctly, this can create a lot of difficulties, depending on the function of that protein. Such a change is called a mutation.
[this could be a good place for an infographic of chromosomes] want to help us? please contact team WaihonaPedia
Mutations in Pitt-Hopkins syndrome
Often, when we examine the DNA in the cells of children with Pitt-Hopkins, we find a mutation in the TCF4 gene on chromosome 18. This gene holds the code for the protein called ‘transcription factor 4’. Transcription is what we call the process of reading the DNA and making a copy that can be used in the machinery that translates these copies to proteins. A transcription factor affects when and how a cell starts making new proteins. We don’t know everything TCF4 does, but we do know that it is important for many processes in the development of the brain.
David Pitt and Ian Hopkins
The name Pitt-Hopkins comes from two Australian doctors, David Pitt and Ian Hopkins, who together described two children in 1978 with the condition we now call Pitt-Hopkins syndrome. We do not exactly know how many people there are today with Pitt-Hopkins. We think about one in 225.000 to one in 300.000 children born has this disorder. These figures are based on the number of known affected individuals in two countries, the United Kingdom and the Netherlands.
First International Consensus Statement
A number of years ago, we decided it would be a good idea if we could agree worldwide on the best way to decide how we know if somebody has Pitt-Hopkins syndrome and how best to help these people and their family. We set up a team called the International Pitt-Hopkins syndrome Consensus Group. Starting in October 2017, we looked for good information that had been published in scientific magazines and added information that we knew about which had not yet been published. Then we discussed all the different topics at a meeting in May 2018. Here, not only doctors and scientists, but also families and other caregivers of 51 people with Pitt-Hopkins syndrome had the opportunity to comment on what we had put together. The text you are reading now is based on the scientific article that was the end result Diagnosis and management in Pitt‐Hopkins syndrome: First international consensus statement in regular English, this is what we agree on about Pitt-Hopkins worldwide.
Diagnosis and management in Pitt-Hopkins syndrome: First international consensus statement. Clin Genet. 2019; 1–17. https://doi.org/10.1111/cge.13506
, published on 24 Jan 2019