question mark with wooden cube on blue background. .jpg

Common Questions

Below you will find some frequently asked questions regarding CUL3-related neurodevelopmental disorder. This list has been compiled to help families gain a better understanding of this condition and its impact on their loved ones.

This is NOT intended to replace medical advice.

What is a neurodevelopmental disorder?

A neurodevelopmental disorder is a condition that affects how the brain develops and functions. These disorders typically emerge in early childhood and can impact a person's learning, behaviour, communication, movement, and more.

What is the difference between a genetic change, a genetic variant or genetic variation, and a genetic mutation?

Genetic terminology can be confusing. The above terms are often used interchangeably. They all essentially refer to a change in a DNA sequence that makes up a gene. Changes in DNA occur all the time - whether spontaneously or passed down from our parents. This genetic variation is what makes us all unique! The effects of a gene change depends on several factors such as where it occurs and how it affects the protein encoded by the gene.

Molecular genetic testing involves determining the significance of changes or variations in a DNA sequence - 'sequence variants'. Technically speaking, there are five categories used by genetics laboratories to classify sequence variants.

Benign - Known not to cause disease.
Likely Benign - Have some evidence suggesting they are unlikely to cause disease.
Variant of Uncertain Significance (VUS) - The effects are unclear due to a lack of available data.
Likely Pathogenic - Have some evidence suggesting they cause disease.
Pathogenic - Have been previously reported with substantial evidence that they cause the disease in question, or they are novel variants in a gene where loss of function is a known mechanism of disease.

You will most likely see CUL3-related neurodevelopmental disorder classified as ‘pathogenic’ or ‘likely pathogenic’ on your lab report.

The term 'mutation' has typically been applied to gene changes considered pathogenic or likely pathogenic. However, by definition, a mutation can be harmful, beneficial, or have no effect. Overtime, cultural references have created a negative association with the word mutation, which is why the word 'variant' is often used instead.

What kinds of genetic variants are possible?

There are a number of different variations that can occur in the DNA sequence of a gene, and these can have varying effects depending on their location and whether they alter the function of essential proteins or regulatory elements.

As always, we recommend asking your geneticist or genetic counsellor to explain the particular variant that is stated on your genetics laboratory report.

What causes changes on the CUL3 gene?

Changes on the CUL3 gene can be inherited or occur spontaneously (i.e., “de novo”).

CUL3-related neurodevelopmental disorder is an autosomal dominant disorder. Autosomal means that the gene is located on one of the numbered (non sex) chromosomes, and dominant means that a single copy of a mutated gene (from one parent) is enough to cause the disorder. An individual with CUL3-related neurodevelopmental disorder has a 50% chance of having a child also affected by the disorder.
When the disorder happens de novo, it means that it has not been inherited from either parent, but rather has arisen in an individual for the first time. Based on our limited knowledge to date, it seems CUL3-related neurodevelopmental disorder most often occurs de novo.

Where can I find more information to help me better understand genetic concepts?

The following websites provide consumer-friendly information on the basics of genetics.

How many individuals are there with CUL3-related disorders?

We currently do not know exachow many people there are globally living with CUL3-related neurodevelopmental disorder. The cases we are aware of are the small number that have been described in genetic databases, the medical literature, and the families who have joined the online support groups. There is likely a larger population out there with undiagnosed CUL3 changes. We hope that by forming this patient advocacy group, we can connect with more CUL3 families.

Do all individuals with CUL3-related neurodevelopmental disorder have kidney issues (i.e., Pseudohypoaldosteronism type 2E)?

No. Gene changes that cause Pseudohypoaldosteronism Type 2E occur in specific regions of CUL3. We recommend you ask your geneticist or genetic conselor to help you interpret your lab report to better understand which type of CUL3 variant you or your child has.

Do all individuals with CUL3-related neurodevelopmental disorder have autism spectrum disorder?

No. When someone is found to have a genetic variant, it does not mean that they will have any particular or all of the features associated with that genetic condition. There are features that can be found more commonly and others less commonly, but every person is still unique.

Do all individuals with CUL3-related neurodevelopmental disorder have seizures?

What is an intellectual disability (ID)?

Intellectual disability (ID) is a condition characterized by significant limitations in both intellectual functioning and adaptive behavior. Intellectual functioning is assessed through standardized intelligence tests, while adaptive behavior refers to the ability to meet the demands of everyday life, such as communicating effectively, performing self-care tasks, and interacting with others in a socially appropriate manner.

Do all individuals with CUL3-related neurodevelopmental disorder have an intellectual disability?

Is there any medical testing that an individual with CUL3-related neurodevelopmental disorder should have?

Individuals with CUL3-related neurodevelopmental disorder may present with a variety of health concerns that should always be discussed with a healthcare provider. Certain medical tests may be recommended based on individual needs to monitor health and development. Testing to consider includes:

Cardiac evaluation – An echocardiogram or other heart tests to assess for congenital heart abnormalities.
Neurological assessment – A neurological exam, electroencephalogram (EEG), and brain MRI to evaluate neurological function, detect seizures, or identify structural brain differences.
Growth monitoring – Regular measurements of weight and height to track growth over time and identify potential concerns.

Additional testing may be necessary based on symptoms, such as bloodwork for metabolic or endocrine concerns, sleep studies for sleep disturbances, or gastrointestinal evaluations for feeding and digestion issues. A healthcare provider can help determine which tests are most relevant for an individual’s specific health needs.

Are there specialists that individuals with CUL3-related neurodevelopment disorder should see?

Since CUL3-related neurodevelopmental disorder can affect multiple aspects of development and health, individuals may benefit from evaluations and ongoing care from various specialists. The specific specialists involved will depend on the person’s unique needs. This could include:

Genetics – To confirm the diagnosis and discuss potential implications.
Developmental Pediatrics – To track developmental progress over time and provide guidance on therapies and interventions.
Cardiology – To evaluate and monitor for congenital heart defects.
Neurology – To assess neurological function and/or to manage movement disorders or seizures.
Endocrinology – To evaluate growth concerns and related hormonal factors.
Gastroenterology – To assess and manage digestive issues, including feeding difficulties, reflux, constipation, or other gastrointestinal concerns.
Psychology – To conduct developmental and behavioral assessments, providing insight into cognitive, social, and emotional needs.
Other Specialists – Depending on individual needs, referrals may also be made for other medical conditions.

If you have concerns about specific symptoms or challenges, consulting a healthcare provider can help determine which specialists may be most beneficial.

What are the common types of therapies recommended for those with CUL3-related neurodevelopmental disorder?

While there is currently no cure or drug treatment for CUL3-related neurodevelopmental disorder, a number of therapies may be helpful in managing some of the symptoms. This may include, for instance, physiotherapy, occupational therapy, and speech therapy.

Physiotherapy can be a valuable tool in managing the range of motor and physical impairments that can happen in CUL3-related disorder by helping improve physical strength and mobility, balance and coordination, and gross motor skills.

Occupational therapy can help address specific developmental, behavioural, and physical needs. This can include activities to help improve fine and gross motor skills, daily living skills, as well as activities to help with sensory processing and self-regulation. Occupational Therapists can also work with parents and caregivers to provide education, support, and guidance on how to best support the child's needs by recommending adaptive equipment, modifications to the environment, and strategies to help with daily activities.

Speech therapy can be a valuable tool to help children improve their communication, language, and social skills. Speech therapists can work with children to: develop strategies for articulation and speech production; improve their understanding of language; and help with expressive language skills like formulating sentences and expressing thoughts and ideas.

Because the effects of CUL3-related neurodevelopmental disorder can vary widely depending on the individual case, it is always best to consult with a qualified healthcare provider for more information on the management of this disorder.

What is the long-term outcome for individuals with CUL3-related neurodevelopmental disorder?

There is still very limited information about the phenotypic spectrum (observed traits and characteristics) and natural history (observation and description over time) of this condition, as there is only succinct medical history for several individuals reported in in the medical literature so far. Without natural history studies, we do not yet know much about the progression of the disorder over the long term. Knowledge on this will continue to evolve as more individuals are diagnosed.

Are there support groups available for parents/caregivers of children who were just diagnosed with a rare genetic disorder?

Yes! We have an online support group that you are welcome to join if you are an individual with CUL3 or are the parent/caregiver of someone affected by CUL3.

You may also want to do some research on supports in your area; it may be the case that your local hospital or genetics department runs a rare disease support group or has information on one that exists in your area.

Are there any other resources (e.g., books, movies, tv shows, etc.) that may be helpful in our journey with CUL3?

Take a look at our Blog for posts on resources like these.