Experts Advocate for Increased Awareness and Screening of Fragile X-Associated Disorders

Researchers Randi and Paul Hagerman from the UC Davis MIND Institute advocate for heightened awareness and screening procedures for fragile X-associated conditions. In their latest publication in New England Journal of Medicine, these physician-scientists point out that despite extensive research, these genetic disorders are still under-recognized by healthcare professionals.

The paper emphasizes the need for screening individuals with autism or intellectual disability for fragile X. "Unfortunately, this recommended practice is not consistently followed," said Distinguished Professor Randi Hagerman, a developmental-behavioral pediatrician and director at MIND Institute.

"It's a simple, typically insurance-covered blood test that is crucial for identifying these conditions."

These conditions are caused by variations in the FMR1 gene located on the X chromosome. They range from a premutation (minor change) to a full mutation with differing health effects.

The most recognized condition is Fragile X Syndrome, resulting from a full mutation and known as the leading inherited cause of intellectual disability and autism impacting learning, development, and behavior.

"Remarkably, many physicians are unaware of Fragile X Syndrome's existence," stated Distinguished Professor Paul Hagerman, associated with the Department of Biochemistry and Molecular Medicine.

Fragile X Syndrome is more prevalent in males than females, with possible characteristics including social anxiety, sensory and sleep issues, large ears, long face, and speech delays.

Carriers of Fragile X may have a premutation but show no visible symptoms. "A sizable portion of the population unknowingly carries these gene mutations," Randi Hagerman noted.

Though some carriers are asymptomatical, health issues can emerge later in life, including:

• Fragile X-associated Tremor/Ataxia Syndrome (FXTAS): A disorder predominantly affecting men over 50, causing tremors, balance difficulties, memory problems, and sometimes resembling Parkinson’s symptoms. The Hagermans' team at MIND Institute discovered it in 2001 while observing symptom similarities among Fragile X patients’ relatives.
• Fragile X-associated Primary Ovarian Insufficiency (FXPOI): Affects women with the premutation, leading to irregular periods, early menopause, and fertility difficulties.
• Emerging Conditions: Research into additional conditions related to the premutation is ongoing, looking at anxiety, depression, and autoimmune anomalies.

The researchers suggest that a full family medical history be taken upon diagnosing Fragile X Syndrome as females with the premutation have a 50% chance of transferring it to their children. Males pass it only to daughters (not sons).

"The diagnosis often leads to additional related condition discoveries within families," Randi Hagerman said.

FXTAS symptoms can mimic those of other disorders, underscoring the importance of screening, Paul Hagerman noted: "Testing helps older adults realize that prior diagnoses of Alzheimer’s or Parkinson’s may actually be FXTAS."

Though no treatments are approved specifically for Fragile X Syndrome yet, various approaches have shown promise, including cannabidiol gel and zatolmilast. Metformin, typically for diabetes treatment, is also being studied as a potential therapy.

"I'm optimistic about the progress of targeted gene therapy research," Paul Hagerman said in relation to his study focus on gene therapy.