Genetic disorders, though rare, offer a glimpse into the complexity of our DNA and how minute changes in it can have far-reaching consequences on human health and development. One such condition is NACC1-related neurodevelopmental disorder, which is caused by mutations in the NACC1 gene. Although rare, understanding NACC1 can provide crucial insights into its symptoms, diagnosis, and potential for treatment.

So What Is NACC1?

NACC1 stands for “Nuclear Accumbens-Associated Protein 1”. This gene plays an essential role in various cellular functions, particularly in brain development and gene regulation. When a mutation occurs in this gene, it can disrupt these processes, leading to a series of developmental and cognitive challenges.

The condition typically presents with neurodevelopmental impairments, which affects an individual’s cognitive abilities, motor skills, and behaviour. These can range from mild to severe, and while the exact prevalence of NACC1-related disorder is not well established due to its rarity, it’s becoming an increasingly recognized cause of intellectual disabilities.

Symptoms of NACC1-Related Disorder

The symptoms of NACC1-related disorder can vary greatly among affected individuals, but the core features are related to developmental delays and intellectual disabilities. Common signs include:

• Developmental Delays: Affected individuals often experience delays in achieving developmental milestones, such as walking, talking, and socializing. Early intervention with therapies can help mitigate these delays to some extent.
• Cognitive and Intellectual Impairment: Most individuals with NACC1 mutations face moderate to severe intellectual disabilities. These may manifest in problems with learning, memory, and problem-solving.
  Behavioural and Social Challenges: Many individuals with this condition exhibit behavioural problems, including traits of autism spectrum disorder (ASD), anxiety, or aggression. These behaviours can make it challenging for individuals to adapt to social settings.
• Motor Coordination Issues: Fine and gross motor skills may be delayed or impaired, leading to challenges with movement, balance, and coordination.
  Seizures: Some individuals with NACC1-related disorder may also experience seizures, though this is not a universal symptom.
• Distinctive Facial Features: In some cases, individuals may show mild facial dysmorphisms, such as a broad forehead, wide-set eyes, or a prominent chin. However, these features are not always present.

Is NACC1 Inherited?

NACC1 mutations are typically inherited in an autosomal dominant manner. This means that only one copy of the mutated gene, inherited from either parent, is enough to cause the condition. In some cases, however, the mutation may occur de novo, meaning it is a spontaneous genetic change not inherited from either parent.

Because of the dominant inheritance pattern, individuals with a mutation in the NACC1 gene have a 50% chance of passing it on to their children. Genetic counseling can be an important resource for families with a history of the disorder.

Diagnosing NACC1 Related Disorders

The process of diagnosing NACC1-related disorder typically involves genetic testing such as Whole Exome Sequencing. This comprehensive approach can identify mutations in a wide array of genes, including NACC1. Another way to identify NACC1 is through targeted Genetic Testing. If there is suspicion of NACC1 involvement, doctors may choose to conduct a targeted test specifically for mutations in the NACC1 gene.

Given the rarity of the condition, a geneticist or a pediatric neurologist is often needed for diagnosis and to guide families through the process of understanding the disorder’s effects.

Treatment and Support

Currently, there is no cure for NACC1-related disorder. However, early intervention may help individuals with developmental delays. Supportive treatments include:

• Speech and Language Therapy: These therapies help individuals with speech delays improve communication skills.
• Physical and Occupational Therapy: These therapies focus on motor skill development and improving coordination.
• Behavioural Therapy: For those exhibiting behavioural problems, therapy can help address challenges related to autism traits, aggression, or social interaction difficulties.
• Seizure Management: In cases where seizures are present, medications may be prescribed to control them and prevent complications.
• In addition to these interventions, personalised care and support tailored to the individual’s needs are crucial in helping them live as independently as possible.

Paige’s Experience with NACC1

At the age of one, Paige got cataracts, which is a cloudy area in the lens of the eye that can lead to vision loss, it came apparent overnight. As a result of this, she had to have both eyes operated on and now wears contact lenses for life to help her sight, but she can only see arm’s length, meaning all interactions need to be close. Paige also has a puree diet, which is a diet that consists of blended food. Due to the developmental delays, she has because of NACC1, she does not chew food, and she uses a soft teat bottle when she drinks.

Paige is usually a happy child, full of smiles and laughter, she loves to people watch and also loves lights and music. She is very sensory with her mouth, loves to chew on anything soft and loves to blow a good raspberry too.

Some days can be hard for not just me, but for her too, we call these irritable episodes, as no one really knows why these happen, but sometimes you can see them coming as she will go a little bit quieter than usual. When these episodes happen, she will be very upset, frustrated, and feeding becomes very difficult, changing Paige also becomes difficult as she becomes very stiff.

Because of NACC1, Paige also suffers with dystonic movements, which means her muscles can be very tense and we can find it hard to dress or hold her because of this. She has undergone three Botox treatments in her feet due to the tension, resulting in her feet turning in and her not having a flat footing, which meant she needed surgery to adjust her tendons for better use of her Standing Aid. Her movements also prevent her from sleeping a lot, it’s like she has to be on the move all the time. So that she doesn’t fall out of bed, she uses a hospital style bed.

Paige takes all of this in her stride and we are extremely proud of her. We have been told that Paige will never walk, but we have hope.

You’ll see in the videos below just how strong Paige is. You’ll also notice she was starting to grow out of her old chair.

Thanks to the incredible support of the Nigel Prosser Foundation, Paige now has the new chair she so desperately needed — something I simply couldn’t afford on my own. We’re beyond grateful. It’s already made such a difference to her comfort and day-to-day life.

Find Out More About Paige’s NACC1 Journey and how we at the Nigel Prosser Foundation helped.

This entire section was written by Paige’s Mum.

The Road Ahead

While research into NACC1-related disorders is still ongoing, it is crucial for families affected by this condition to stay informed and connected with support networks. With the advancement of genetic research and therapies, there may be hope for better management and even treatments in the future. It’s also important to be proactive in seeking early diagnosis, genetic counseling, and appropriate interventions. With the right support, individuals with NACC1-related disorder can lead fulfilling lives, even though they may face significant challenges along the way.