4 DNA Testing Before Birth
4 PRENATAL DNA DIAGNOSIS
AS mentioned in section 3, most people with Pitt Hopkins syndrome do not have a brother or sister with Pitt Hopkins. The chance that parents who have had a child with Pitt Hopkins have another child that also has it (the 'recurrence risk') is low, around 2% . It is unlikely that a baby before it is born will be diagnosed with Pitt Hopkins during a prenatal ultrasound, as Pitt Hopkins doesn't cause abnormalities that are visible on such an ultrasound.
Even though Pitt Hokpins is usually caused by a de novo DNA mutation, it is still possible that the mutation comes from a cell with the faulty DNA that has split into more eggs or sperm cells (this is called a 'germ line mutation'). For this reason, families with a previous affected child should be offered the possibility of 'prenatal diagnostic testing', which means that DNA of the baby in the womb is tested (R6). Such testing is reliable if the genetic change in the first child with Pitt Hopkins (the 'index patient' in genetic terms) is known. Testing can be performed through either chorionic villous sampling, amniocentesis, or pre-implantation genetic testing after in vitro fertilization.
It is possible to find out whether an unborn child has a matuation in the DNA coding for Transcription Factor 4 even if parents have not already had a child with Pitt Hopkins. This can be done with non-invasive prenatal testing (NIPT). However, we feel that this would not be useful at present, because we do not yet know enough about which changes in DNA lead to which effects in the child (R7). If such testing is offered anyway, pre-test advice should include discussions about reliability and informative value of the results, as well as questions about what is good to know and what not, and what would be good to do and what not based on the results of such tests.
4.1 Recommendations
R6 Prenatal testing should be offered to families in which the diagnosis of PTHS in the index patient is molecularly confirmed.
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R7 Prenatal testing for PTHS outside of a known familial genetic alteration remains challenging due to the current difficulty in interpreting reliably all variants that will be obtained. Use of this type of testing as a screening method is not recommended at the present time.
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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 janv. 2019