What is CRELD1?
CRELD1 (Cysteine Rich With EGF Like Domains 1) is a Protein Coding gene. Sequence changes in the CRELD1 gene are typically associated with the cause of atrioventricular septal defect (AVSD).
Diseases associated with CRELD1 include Atrioventricular Septal Defect 2 and Partial Atrioventricular Septal Defect Without Ventricular Hypoplasia.
Very little is known about the link between CRELD1 and epilepsy. In fact, if you Google 'CRELD1 and epilepsy' you will find that nothing has been published. Zero.
What we have learned is that new types of sequence changes in different parts of the CRELD1 gene can cause an extremely rare genetic disorder, when both copies of the gene don’t function properly (autosomal recessive inheritance). This manifests as a wide range of neurodevelopmental disorders, ranging from mild movement disorders to severe developmental and cognitive delays. This newly identified CRELD1-related disorder is also characterised by multiple, frequent, treatment resistant epileptic seizures, adrenal insufficiency, severe bilateral neural hearing loss, immature eye development, acute respiratory distress and submucosal cleft palate to name a few.
There are five things that are known to be associated with CRELD1-related disorder:
1) Heart issues - atrioventricular septal defect (AVSD)
2) Neuromuscular issues
3) Seizure activity
4) Global developmental delay and cognitive delay/ learning differences
5) Respiratory issues and now possibly immune-related issues.
Not all children diagnosed will necessarily have all of these conditions. The most common characteristic found in the children who have been found to have CRELD1-related issues is intractable seizures. However, it is thought that there are are likely to be other children with different presentations, who are lesser known because of how the studies have been conducted.
Also, not all children with sequence changes in the CRELD1 gene will have severe global and developmental/cognitive delays. Because of the National Institutes of Health (NIH) study, CRELD1 is now on the map with genetic testing.
It’s important for any new parents that have their child diagnosed with CRELD1-related squence changes via genetic testing, that they know of the full range of possibilities their children might experience. You will learn from our CRELD1 Warriors that all of them really are unique in their conditions and demonstrate the full spectrum of capabilities.
While there is currently nothing published in medical literature, there is an ongoing research study being managed out of Yale University and GeneDx. In the meantime, we continue to share everything we learn from our own experiences and with the other families in our CRELD1 family.
We are the CRELD1 Warriors and we are fighting back....
Currently there is no known cure for this condition and all children seem to display varying degrees of symptoms. There are various combinations of treatments that have provided some improvement for children diagnosed. The main challenge for all children is getting their seizures under control. We know that some of the children with CRELD1 have responded well to the anti-epilepsy drugs listed below.
Please note, this should not be treated as medical advice, it is simply based on parent's experience. You should always consult your neurologist regarding any treatment options for your child.
- Chlobazam (sold under the brand names Frisium, Onfi and others)
- Topiramate (sold under the brand name Topamax)
- Phenobarbital (also known as phenobarbitone or phenobarb, or by the trade name Luminal)
- Buccal Midazolam (sold under the brand name Versed among others)
- Epidiolex (and other cannabidiols)
- Ketogenic Diet (although to be treated with caution in some cases)
- Sodium Valproate (also known as Epilim, Episenta, Epival, Convulex)
The following medications should be avoided where possible:
- Phenytoin (sold under the brand name Dilantin among others) - all children reacted very badly to this. The Ketogenic Diet should also be treated with caution.
You can find a list of all available anti-seizure medication on the Epilepsy Society website here.
Connect and support families in the UK and Ireland to offer mutual support and information, while linking to the wider global CRELD1 community.
To support and drive research to produce effective treatments for CRELD1.
To do this we will work collaboratively with groups across Europe and the world to advance research, understanding and the quest for better treatment.
To provide information, resources and signposting to families and clinicians.
We also seek to support newly diagnosed families and their clinicians by linking to research and local and international expertise.