Frequently Asked Questions

Genetic Information

  • The NARS1 gene provides instructions for making an enzyme called asparaginyl-tRNA synthetase. This enzyme plays a crucial role in building protein, which is essential for our bodies to function properly.

  • NARS1 Disorder can be inherited or arise spontaneously (de novo). Genetic counseling is recommended for guidance on reproductive planning when there is a family history of NARS1 Disorder.

  • Everyone has two copies of each gene, one from each biological parent. For children with an inherited NARS1 Disorder, both parents are carriers of a genetic change (variant) in the NARS1 gene and each passes it to their child. When the child inherits two copies of NARS1 with a variant—one from each parent—the gene doesn’t function properly. This inheritance pattern is called autosomal recessive. If both biological parents are found to carry the variant, there is a 25% (or 1 in 4) chance that any future child will inherit the disorder. 

    Note: There is emerging evidence of another inherited NARS1 Disorder with adulthood onset nerve damage, also known as Charcot-Marie-Tooth. This disorder resembles some of the symptoms our children experience but it is a different disorder with a different inheritance pattern.

  • Genetic counseling is recommended for guidance on reproductive planning when there is a family history of NARS1 Disorder. Carrier testing is a type of genetic testing done to find out if you carry a change (variant) in the NARS1 gene that can cause a NARS1 Disorder. Most often, being a carrier for one of these changes does not mean that you have the disorder yourself, but that you may have a chance to pass it on to a child. Carrier screening for unaffected siblings and other family members is recommended at the time of planning a pregnancy or if they are already pregnant.

  • Carrier screening is not recommended for children under the age of 18, as it is not helpful in the medical care of healthy children. Once your children are 18 or older they can decide if they would like to pursue carrier screening, prior to considering reproductive options.

  • In some cases, NARS1 Disorder arises spontaneously because of a de novo variant in one copy of the NARS1 gene. This means the variant occurs for the first time in the child, rather than being inherited from the parents. A de novo variant happens randomly, either in the egg or sperm before conception or early in the baby's development.

    If neither parent carries the NARS1 variant, the chance of having another child with the disorder is very low (less than 1%). The residual risk is due to a phenomenon known as ‘gonadal mosaicism’, in which a parent may have a cluster of cells within their reproductive organs that carries the genetic alteration in NARS1. This cannot be detected on a blood test and there is currently no effective way to test for gonadal mosaicism.

Diagnostic Information

  • Diagnosing NARS1 Disorder involves genetic testing. Since individuals with NARS1 Disorder have symptoms that overlap with other conditions, it is possible that multiple rounds of genetic testing are ordered before finding a NARS1 variant. The testing may include karyotyping, gene panel, and finally a whole exome or whole genome testing before these variants are discovered. The testing may involve a mouth swab or blood collection for the child and/or both parents.

  • Genetic testing identifies variants, which are changes in the DNA sequence that make up a gene. If a variant is found on your child’s genetic testing, there are three different types of diagnostic classifications it can be reported as: “pathogenic/likely pathogenic”, “variant of uncertain significance (VUS)”, “benign/likely benign”. 

    If your child’s genetic variant(s) are reported as ‘pathogenic’ or ‘likely pathogenic’, it means there is sufficient evidence that the variant alters the NARS1 gene function and is causative of NARS1 Disorder.

    If your child’s genetic variant(s) are reported as a “variant of uncertain significance (VUS)”, it means there is not sufficient evidence that the variant alters the NARS1 gene function. 

    Because NARS1 Disorder is rare, there is still much to learn. It is common for genetic reports to include a VUS and your genetic counselor can help you understand what this result may mean for your child. Even if a variant is classified as uncertain, doctors may still consider it significant based on your child's symptoms and other test results. As research advances and awareness of the NARS1 Disorder expands, new evidence may emerge, leading to the reclassification of these variants as either “pathogenic” or “benign.” You can enroll your VUS at Brain Gene Registry to receive updates on reclassifications.

    Many genetic variants are harmless and do not impact health. If your child's genetic report lists a variant as benign or likely benign, it means that it is not expected to contribute to NARS1-related symptoms.

  • Genetic testing technology and knowledge are rapidly evolving. If your child’s genetic testing was performed before 2020, it may not have included the NARS1 gene, which was first linked to global neurodevelopmental delay and other neurological symptoms that year. If your child was tested before 2020, consider speaking with your healthcare provider about updated testing or applying through Probably Genetic which has a no-cost genetic testing program in the United States.

Medical Information

  • NARS1 Disorder can present with a range of symptoms, and the severity and specific challenges vary from child to child. We are continuously learning about NARS1 Disorder so we will update this as we know more. These are some possible symptoms of NARS1 Disorder: 

    • Smaller Heads: Some children might have smaller heads, a condition called microcephaly.

    • Long Fingers or Toes: Their fingers or toes might be longer than usual.

    • Seizures: They may experience different types of seizures, which can affect their brain activity.

    • Walking Difficulties: Some kids might have trouble walking on their own or may even need help moving around.

    • Speaking Issues: They might find it hard to talk or may only be able to say a few words.

    • Eating Problems: Some children may struggle to eat on their own, which can sometimes require a feeding tube.

    • Muscle Spasms: They may have muscle spasms that can be uncomfortable.

    • Tingling or Numbness: Kids might feel tingling, numbness, or pain in their arms and legs.

  • Children with NARS1 Disorder may benefit from seeing various specialists depending on their symptoms, including:

    • Neurologist and Developmental Pediatrician: To address and assess any neurological or behavioral symptoms such as seizures/epilepsy, delay in hitting milestones, like speech or coordination issues.

    • GI (Gastrointestinal) Specialists: To address any issues with feeding, weight gain, gagging, or vomiting.

    • Neuromuscular Specialist: To assess any issues with neuropathy that may show up on tests called EMGs

    • Ophthalmology: To assess visual or processing concerns (trouble understanding things and communicating back)

    • Genetic Counselors: To understand the genetic aspects of NARS1 Disorder.

    • Physical, Speech, and Occupational Therapists: To assist with movement, communication, and daily activities. It is recommended to start these therapies as early as possible. 

    Your healthcare team can guide you on which specialists are most appropriate for your child's needs.

  • The Scientific Publications page on this website has information for your doctors on current research and developments.

  • NARS1 Disorder is rare, with around 100 known cases worldwide in children and adults. Because of this, we know it's important to build a community and drive ongoing research. 

  • Enroll in RARE-X on our website and Join the patient registry here. By contributing your information, you’re helping to speed up the development of treatments and potentially life-saving therapies.

Treatment Options

  • Right now, there are no specific treatments that target NARS1 Disorder directly. However, doctors focus on managing symptoms based on each person’s needs. This might include physical therapy, speech therapy, medications for seizures if needed, and other supportive care to help improve quality of life. Because NARS1 Disorder can affect people in different ways, treatment plans are personalized for each individual.

  • Researchers are working hard for a cure. Gene therapy has exciting potential, but at this time, there are no approved gene therapies for NARS1 Disorder. Researchers are exploring different treatment approaches, including gene therapies which may correct or support the function of the NARS1 gene. While these treatments are still in early stages, advancements in rare disease research bring hope for future therapies.

Support Information

  • Depending on who you are speaking to, a few simple facts about NARS1 Disorder can be helpful. If you find the person would like to know more, there is certainly more information available to them, however these simple facts might be helpful when put on the spot:

    • It is a genetic disorder that can cause medical challenges and delays in development that require assistance and planning.

    • Individuals with NARS1 Disorder get joy from many of the same things as other children.

    • Individuals with NARS1 Disorder may express their feelings in other ways, such as with sounds, movements, and touch.

  • Connecting with other families can provide support and valuable insights on daily life. The Rory Belle Foundation offers a Facebook support group where you can share experiences, ask questions, and find community. Join here. We also have a WhatsApp community for families to keep connected and provide support. Contact us to get connected!

  • When discussing NARS1 Disorder with your child’s medical team, it can be helpful to provide a concise summary of the disorder and its specific impact on your child. Consider the following key points:

    • Diagnosis & Genetics: NARS1 Disorder is a rare genetic disorder caused by variants in the NARS1 gene, which affect protein synthesis and lead to neurological and developmental challenges.

    • Symptoms & Medical Needs: Common symptoms include developmental delays, movement difficulties, and neurological issues. Your child’s specific symptoms and medical history should be shared with specialists.

    • Current Management: Describe any ongoing therapies, medications, or interventions your child is receiving. If applicable, mention evaluations or follow-ups with specialists (e.g., neurology, GI, ophthalmology).

    • Genetic Testing Results: If available, bring a copy of your child’s genetic test report to share with providers. If the variant is classified as a variant of uncertain significance (VUS), discuss the need for continued monitoring and possible reclassification.

    • Specialist Coordination: Since NARS1 Disorder affects multiple systems, care coordination between specialists (e.g., neurologist, genetic counselor, therapists) is essential. Discuss the need for referrals or additional assessments.

    • Agree on a communication channel. Ask your medical team the best way to stay in touch between appointments (portal, email, phone, etc).

    It may also be useful to provide your physician with links to trusted resources, such as research registries or patient advocacy groups, to help them stay updated on advancements. Below are some resources:

     Additionally, you can contact us via our website or at this email: hello@therorybellefoundation.org