ARX-related disorders are a group of genetic conditions that mainly affect brain function and are often linked to intellectual disability.
The symptoms of ARX-related disorders can vary widely, even among members of the same family.
Development and Epileptic Encephalopathy 1 (DEE1): DEE1 is characterized by seizures that cause sudden stiffness or tension in the body. These seizures usually start within the first year of life, and intellectual disability is common. Some infants may lose skills they had already learned, like sitting or rolling over.
X-linked Lissencephaly 2 (LISX2): LISX2 affects brain and genital development. It’s also known as X-linked lissencephaly with abnormal genitalia or XLAG. The brain has a smooth appearance, and there may be abnormal genital development, such as a small penis, undescended testes, or ambiguous genitalia. Intellectual disability and seizures are often present, and the condition is often fatal for individuals with an X and Y chromosome within the first few days or months of life. Individuals with 2 X chromosomes usually have mild or no symptoms.
Partington Syndrome: Partington syndrome includes mild to moderate intellectual disability, speech difficulties, and involuntary hand movements. Some people may also have seizures, behavioral issues, and unique facial features. Symptoms usually start in infancy or early childhood.
Proud Syndrome: Proud syndrome causes severe intellectual disability, seizures, and a brain defect called agenesis of the corpus callosum. It may also lead to urologic problems, such as undescended testes, abnormal opening of the penis, and underdeveloped kidneys.
X-linked Intellectual Developmental Disorder: This diagnosis is given to individuals whose symptoms don’t match any of the specific syndromes listed above.
There is no cure for ARX-related disorders. Treatment for these conditions is directed at managing an individual’s specific symptoms. The goal of treatment is to optimize the individual’s abilities. Children with the condition will often benefit from receiving early intervention and other supportive services beginning at a young age. Many of the seizures associated with ARX-related disorders tend to be difficult to treat.
ARX-related disorders are caused by pathogenic variants in the ARX gene exhibit X-linked recessive inheritance. This means that one pathogenic variant is enough to cause the disease in both individuals assigned male at birth (who have one X chromosome and one Y chromosome) and individuals assigned female at birth (who have two X chromosomes) may experience symptoms depending on how many copies of the X chromosome that has the pathogenic variant are turned on in the cells.
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Written August 2024
