Management and Surveillance
PADDAS
Currently, there is no known cure for a PUM1-related disorder. For PADDAS early intervention and education programs can maximise learning and social development, and medications can help manage some symptoms.
Close supervision by a paediatrician or physician experienced in caring for people with intellectual disability is recommended, so that appropriate educational and allied health support can be put in place.
Parents should be encouraged to promptly discuss any concerns about possible seizures, neurological symptoms (e.g. unsteady gait, tremor, movement disorder) or behavioural or mental health conditions with their child’s doctor so that these symptoms can be appropriately investigated and referral to a specialist (neurologist or psychiatrist) can be arranged.
Suggested surveillance:
- Developmental delay/ intellectual disability: Close developmental surveillance by a paediatrician/ physician with appropriate referral for early intervention and ongoing support at school and on school leaving.
- Seizure disorder: Review by paediatrician/ GP / physician if any concerns regarding possible fits /’funny turns’/ blank episodes with a low threshold for referral to a neurologist/ EEG.
- Movement disorders (ataxia/ unsteadiness, hypotonia/floppiness, and spasticity/ increased tone): Assessment by a neurologist.
- Eye conditions including strabismus (a ‘turned’ eye), cortical visual impairment (difficulties seeing) and ptosis (droopy eyelids): Assessment by an opthalmologist.
PRCA
Currently, there is no known cure for PRCA. However, close supervision by a neurologist/ physician experienced in caring for people with adult-onset movement disorders should be in place, so that appropriate allied health and psychological support can be put in place.
Genetic counselling
The majority of individuals with PADDAS have been reported to have a new [‘de novo’] change in the PUM1 gene, which is not present in the blood sample from their mother or father. These individuals typically come from families that have no family history of intellectual disability, and the PUM1 gene change has occurred for the first time in the person with the disorder.
As with other sporadic disorders, it is possible that one parent may have the PUM1 mutation in some of their eggs 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. Referral to a genetics team to discuss this possibility can be helpful if planning another pregnancy.
What are the chances of an individual with PADDAS or PRCA having a child with a PUM1-related disorder?
Both PADDAS and PRCA are caused by an autosomal dominant mutation. This means that it affects an autosomal gene which is a gene located on a numbered chromosome (in this case chromosome number 1) and the condition affects males and females in the same way. Dominant means that the gene change need only occur in one of the pair of genes to cause the health condition.
While it is unlikely that an affected individual with PADDAS with moderate or severe intellectual disability will partner and have children, individuals with PRCA or those that are more mildly affected with PADDAS could have children. An individual with a PUM1 mutation has a 1 in 2 (50%) chance of passing on that gene change to a baby in each pregnancy. A child that inherits the PUM1 change may be similarly, more mildly, or more severely affected than their parent.
Carriers of or individuals affected by genetic conditions have choices when planning children and these options can be discussed with a clinical genetics service. Genetic counselling is available through a local genetic service when planning a pregnancy and in early pregnancy.