Brunner syndrome

Overview

Brunner syndrome is a rare genetic disorder linked to abnormalities in behavior and intellectual development, caused by mutations in the monoamine oxidase A (MAOA) gene. It was first identified in a Dutch family where affected males exhibited impulsive and aggressive behavior, mild intellectual disability, and abnormal neurotransmitter metabolism. The syndrome is X-linked, primarily affecting males, and is associated with altered breakdown of key neurotransmitters such as serotonin, dopamine, and norepinephrine.

Causes

Brunner syndrome is caused by mutations in the MAOA gene, located on the X chromosome. This gene encodes the enzyme monoamine oxidase A, which is responsible for the degradation of monoamine neurotransmitters. When this enzyme is deficient or nonfunctional due to a mutation, it leads to an accumulation of neurotransmitters in the brain, affecting mood, behavior, and cognitive function.

Since the gene is located on the X chromosome, Brunner syndrome follows an X-linked recessive inheritance pattern. Males (who have only one X chromosome) are more likely to be affected if they inherit the mutated gene, whereas females are usually carriers and typically do not show symptoms due to the presence of a second, normal X chromosome.

Symptoms

Symptoms of Brunner syndrome can vary in severity but commonly include:

• Impulsive or aggressive behavior

• Mild to moderate intellectual disability

• Sleep disturbances

• Emotional instability or mood swings

• Abnormal response to stress

• Increased startle response or exaggerated reactions

• Speech or language delays

• Seizures or abnormal EEG patterns (in some cases)

Behavioral issues such as aggression, arson, or hypersexuality have been reported in some documented cases, particularly in the original Dutch family described in the medical literature.

Diagnosis

Diagnosis of Brunner syndrome involves a combination of clinical assessment, biochemical analysis, and genetic testing. Diagnostic steps may include:

• Behavioral and developmental evaluation – focusing on aggression, cognitive delay, and emotional regulation

• Urine testing – to measure levels of monoamine metabolites (e.g., increased levels of serotonin, dopamine, and norepinephrine metabolites may be found)

• Genetic testing – to identify mutations in the MAOA gene

• Family history analysis – especially in cases with multiple affected males across generations

Treatment

There is no specific cure for Brunner syndrome. Treatment is supportive and focuses on managing behavioral and cognitive symptoms. A multidisciplinary approach is typically used and may include:

• Behavioral therapy – to help manage aggression and impulsivity

• Educational support – for learning difficulties or developmental delays

• Psychiatric evaluation and medications – including possible use of mood stabilizers or antipsychotic medications (with caution, given neurotransmitter involvement)

• Speech and occupational therapy – for language and motor skill development

• Family counseling and support – to assist with behavioral management strategies

Prognosis

The long-term outlook for individuals with Brunner syndrome depends on the severity of symptoms and access to early intervention and support. While intellectual and behavioral challenges are persistent, they may be managed with structured care and individualized therapies. Some individuals may be at higher risk for socially disruptive behavior, especially without early behavioral management. As awareness of the syndrome grows and genetic testing becomes more accessible, earlier diagnosis and intervention may improve outcomes and quality of life.