CHEDDA is caused by gene changes in a specific part of the ATN1 gene called the ‘HX repeat motif’. In all affected children known to date the genetic change causing CHEDDA arose for the first time in the child, otherwise known as a ‘de novo’ genetic condition. This means that genetic testing of the affected child’s parents does not show that they carry the same gene change.
A different condition, dentatorubral-pallidoluysian atrophy, or DRPLA, is an inherited progressive brain disorder, that typically starts in adulthood, and causes involuntary movements, mental and emotional problems, and a decline in thinking ability. DRPLA is caused by a very different type of genetic change in the ATN1 gene, called a ‘CAG trinucleotide repeat expansion’.
For CHEDDA we are still researching how the changes in the HX repeat motif of the ATN1 gene cause this condition: the gene changes likely affect how the ATN1 gene works within the cells of the developing embryo and foetus, affecting how it controls the turning on and turning off of other genes in order to regulate how a baby grows and develops.
How do you test for CHEDDA?
The testing can be arranged by a paediatrician or a geneticist and involves a blood or saliva collection. The DNA is tested for changes in the DNA code of the ATN1 gene. The changes identified are de novo, meaning that they are new changes found in affected individuals and neither parent is likely to be a carrier.
How is CHEDDA inherited?
Individuals with CHEDDA typically come from families that have no family history of neurodevelopmental disorders or congenital conditions. The ATN1 gene change occurs for the first time in the person with the condition.
On occasion, one parent may have the ATN1 mutation (gene change) in some of their egg or sperm cells but not be affected, as no other organ in their body has the mutation. This is called germline mosaicism and means that there is a very small chance that they may have another affected child. It would be important that parents of an individual with CHEDDA discuss this possibility with their local genetics team if they were planning another pregnancy.
What are the chances of an individual having a child with an ATN1-related disorder?
While it is unlikely that an individual with CHEDDA who is severely affected will partner and have children, a carrier of a ATN1 mutation that does go on to have children will have a 50% chance with each pregnancy of passing on the ATN1 mutation. Children who inherit an ATN1 mutation from their parent will experience a similar level of challenges as their parent; some may even experience difficulties and symptoms not seen in their parent. Genetic counselling is available through the local genetic service when planning a pregnancy and in early pregnancy.