Bosch-Boonstra-Schaaf Optic Atrophy Syndrome (BBSOAS) is a rare genetic condition affecting the NR2F1 gene. It’s associated with visual impairment, developmental delay, seizures or epilepsy, and intellectual disability. Each person with BBSOAS is affected differently.
What causes BBSOAS?
BBSOAS is caused by a change (variant) in the NR2F1 gene or the loss (deletion) of one copy of this gene. Genes, made of DNA, provide instructions for our growth and development. They are organized into structures called chromosomes, which contain our genetic information and are located inside our cells.
The NR2F1 gene, located on the long “q” arm of chromosome 5 at region 5q15, produces the NR2F1 protein, which regulates many other genes and influences brain and visual system development.
BBSOAS occurs when one copy of the NR2F1 gene is affected, while the second copy remains functional. This condition is autosomal dominant, meaning it occurs when only one copy of the gene is altered.
Symptoms of BBSOAS
People with BBSOAS may have a range of symptoms, including:
Developmental delay
A condition where a child does not reach developmental milestones (such as walking or talking) at the typical age. It may affect motor skills, speech, or social interaction.
Intellectual disability (ID) or learning difficulties (LD), from mild to profound
Conditions where individuals experience challenges in cognitive abilities. This ranges from mild difficulties in learning and reasoning to more severe impairments that significantly affect daily functioning.
Visual impairment
General term for conditions affecting vision. It can include various types, such as:
Optic nerve atrophy: Damage to the optic nerve, which carries visual signals from the eye to the brain, leading to partial or complete vision loss.
Optic nerve hypoplasia: An underdevelopment of the optic nerve, resulting in impaired vision, which can vary in severity.
Cortical visual impairment (CVI): Damage to the brain areas that process visual information, affecting the ability to see clearly even when the eyes are healthy.
Alacrima (reduced or absent tear production)
A condition where the body does not produce enough tears, leading to dry eyes and potential discomfort or eye infections.
Manifest latent nystagmus (involuntary eye movement)
A condition where the eyes move uncontrollably, which can affect vision clarity and focus.
Repetitive behavior
Actions or behaviors that are performed repeatedly, often seen in conditions like autism. These can include hand-flapping, rocking, or repeating certain words or actions.
Autism spectrum disorder (ASD)
A developmental disorder affecting social skills, communication, and behavior. It can vary in severity and is often characterized by repetitive behaviors and difficulty with social interactions.
Speech and language delay or non-verbal communication
A delay in developing spoken language or difficulty using verbal communication. It leads some individuals to rely on non-verbal methods, like gestures, sign language, or augmentative and alternative communication (AAC) devices.
Swallowing problems (oromotor dysfunction)
Difficulty in swallowing food or liquids due to issues with the muscles and coordination of the mouth and throat, which can lead to choking or poor nutrition.
Low muscle tone (hypotonia)
Reduced muscle strength and control, making it harder for individuals to maintain posture, move, or perform physical tasks.
Seizures or epilepsy, including infantile spasms and febrile seizures
Seizure disorders where the brain experiences abnormal electrical activity, leading to seizures. Infantile spasms occur in infants, while febrile seizures are triggered by high fever in young children.
Attention deficit hyperactivity disorder (ADHD)
A condition characterized by inattention, hyperactivity, and impulsiveness. This affects an individual’s ability to focus, stay organized, and follow through with tasks.
Hearing impairment
Partial or complete inability to hear, which can range from mild hearing loss to profound deafness, impacting communication and social development.
Symptoms vary among individuals
Those with changes in the DNA-binding domain (DBD) of the NR2F1 gene have more severe symptoms. While those with whole-gene deletions and truncating mutations tend to have moderate to mild symptoms. BBSOAS is a static encephalopathy and is not progressive.
Other possible features include:
Mild and inconsistent facial features
MRI images may show impact to visual pathways and a thin corpus callosum (the bundle of nerve fibers connecting the two brain hemispheres)
Inheritance pattern
BBSOAS is an autosomal dominant disorder. Most cases are de novo, meaning the variant was not inherited from either parent, but occurred early in the reproductive process.
Familial cases are also known. The chance of unaffected parents with one affected child having a second affected child is less than 3%. While an affected parent has a 50% chance of passing the condition to their child.
Diagnosis of BBSOAS
BBSOAS is diagnosed by a geneticist through chromosome microarray, whole exome sequencing, or NR2F1 sequencing.
Prevalence of BBSOAS
BBSOAS is extremely rare. As a foundation, we know of around 500 cases around the world. More diagnoses are expected as awareness and genetic testing increase.
Incidence rate
It’s estimated that BBSOAS may affect 1 out of every 250,000 babies born each year (Schaaf, 2023).
It’s predicted that approximately 4,000 babies are born annually with a change in their NR2F1 gene around the world.
Management of BBSOAS
Individuals with BBSOAS should be managed by a multidisciplinary team, including a geneticist, pediatrician and ophthalmologist, to monitor development, vision and behavior.
Treatment may include physical therapy (physiotherapy), occupational therapy, speech therapy, vision therapy, and behavioral therapy.
Evaluations by neurology, respiratory, ophthalmology, audiology, and gastroenterology specialists are also recommended.
Most individuals with BBSOAS will require lifelong intensive therapies and support. While some may live semi-independently and even become parents, most will need significant assistance as adults.
Research and future treatments
Research into treatments for BBSOAS as well as its features like optic atrophy and CVI is ongoing. The NR2F1 Foundation is working with scientists to fund and discover future treatments.
Life expectancy
Individuals with BBSOAS are expected to have a normal life expectancy.