3.6 Chance of a sibling also having Pitt Hopkins

3.6 Pattern of inheritance

When people have a child who is diagnosed with Pitt Hopkins, they often want to know how high the chance is that they will have another child with this syndrome if they get pregnant again. They want to know about the 'pattern of inheritance'.

In fact, children with mutations in TCF4 that lead to typical Pitt Hopkins Syndrome usually don't get this error in their DNA from their parents. The mutation is then called 'de novo', which is Latin for 'anew'. Because of this, the chance that a brother or sister of a child with Pitt Hopkins will also have this syndrome is low. 

There are only a few cases know in which the mistake in the DNA was inherited from either the father or the mother. Based on the reported cases and the clinical experience of the doctors who helped write this text, the chance that a child with Pitt Hopkins syndrome will have a brother or sister who also has Pitt Hopkins is at maximum 2 % (R4). As far as we know, no persons with typical Pitt Hopkins have ever had children themselves. 

As described in section 3.4, some people are known to have TCF4 variants without fulfilling the diagnostic criteria of Pitt Hopkins. Sisters and brothers of some of these people run a 50% chance of inheriting the same mistake in TCF4.^29,36