How Common are Medical Problems in Fragile X Syndrome?

Are medical problems more common in individuals with Fragile X syndrome than in typically developing children?

To help answer that question and guide pediatricians in caring for individuals with FXS, clinicians from the Fragile X Clinical and Research Consortium working with Dr. Sharon Kidd, former FXCRC national coordinator, set out to determine the most common medical problems found in individuals with FXS.

Common FXS Medical Problems and Their Prevalence

Using data from the first phase of a project funded by the CDC, we analyzed information from FXS patients collected by clinicians working at FXCRC clinics between 2005 and 2011. This data was collected one time only for each patient. We also reviewed the literature, and a full report of the findings, Fragile X Syndrome: A Review of Associated Medical Problems, was published in the journal Pediatrics, on October 6, 2014.

The prevalence of common medical problems found in individuals with FXS are:

• Recurrent ear infections (>4 times per year) — 52.5%
• Strabismus (eyes not properly aligned with each other) — 16.4%
• Seizures — 10%

Some Medical Problems Are Not Increased in FXS

Some medical problems that have been a concern for caregivers of people with FXS did not turn out to occur more frequently than in typically developing individuals, based on prior literature and the FXCRC database.

For example, although low birth weight and prematurity were not examined in previous studies, the FXCRC data suggests the frequency of mitral valve prolapse and tics is not higher than in typically developing infants.

Management and Follow-Up of Selected Medical Problems in FXS

The pediatrician should look for and ask about symptoms that might be related to these problems at routine yearly well-child visits and should refer to specialists for further evaluation and management if needed. The type and timing of follow-up for these problems will depend on the severity and whether medication intervention is implemented.

Ear Infections

Since children with FXS frequently have expressive language delays, it is important that all otitis media and any otologic issues be treated promptly and appropriately. Hearing testing may be considered if there is concern about a child’s hearing.

Seizures

For concerns about episodes that might be seizures, an electroencephalogram (EEG) evaluation should be obtained along with a neurology referral. Special attention should be given to children with FXS and ASD since they seem to be particularly at risk for epilepsy. Ambulatory EEG can be used to distinguish behavioral spells from seizures. Typically, patients would be treated after two documented seizures with anticonvulsants that are least likely to cause sedation or behavioral aggravation, with a view to discontinuance of treatment after an individual with FXS is seizure-free for two years.

Ocular (Eye) Disorders

As strabismus and other ocular disorders, such as refractive errors, are common in children with FXS, pediatricians should monitor these conditions and refer children during the first three years for evaluation by a pediatric ophthalmologist or optometrist. This should be followed by yearly eye exams to continue to monitor for refractive errors.

Purpose of the Study

One of the goals of this Pediatrics paper was to support pediatricians in their treatment of individuals with FXS. This was accomplished by updating the evidence for the medical problems associated with FXS and providing evidence for the May 2011 AAP guidelines, Health Supervision for Children with Fragile X Syndrome.

Additional research questions are being considered based on the data collected in the second phase of a CDC-funded large and comprehensive study that follows children living with FXS forward in time through adulthood. Examples of questions being considered are:

• What is the relationship between behavioral symptoms and language?
• What are the barriers to social participation and daily living activities?
• What is the severity of behavioral problems?

Also see information and results from the FORWARD-MARCH Registry and Database.

Study Co-Authors

• Deborah Barbouth, MD – Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL
• Elizabeth Berry-Kravis, MD, PhD – Departments of Pediatrics, Neurological Sciences, and Biochemistry, Rush University Medical Center, Chicago, IL
• Robin K. Blitz, MD – Developmental Pediatrics, Barrow Neurological Institute at Phoenix Children’s Hospital and Department of Pediatrics, University of Arizona College of Medicine, Phoenix, AZ
• Carol Delahunty, MD – Department of Developmental and Rehabilitation Pediatrics, Cleveland Clinic, Cleveland, OH
• Ave Lachiewicz, MD – Departments of Pediatrics, Psychiatry, and Behavioral Sciences; Duke University Medical Center, Durham, NC
• Dianne McBrien, MD – Department of Pediatrics, University of Iowa Medical Center, Iowa City, IA
• Jeannie Visootsak, MD – Departments of Human Genetics and Pediatrics, Emory University, Atlanta, GA