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When evaluating the significance of some intervention, randomized-control trials are our gold standard.  However, randomized-control trials are usually constrained by time and hindered by some bias.  In order to better understand pathology and the long-term effects of treatment, medical researchers, physicians and others need to follow a cohort or group of research participants with a chronic disease or condition for several years or decades.  In other words, a prospective and longitudinal study can provide a comprehensive understanding of disease, and thus make an invaluable contribution to evidence-based practice.

Unfortunately, it’s difficult and cumbersome to set up a good longitudinal study with fixed definitions.  Doing so requires an immense investment of resources.  Consequently, when an excellent longitudinal study comes along—especially one that examines a rare disease which may have otherwise gone unstudied—it deserves our attention.  I have found one such study: a 20-year look at Rett syndrome which was funded by the Australian government.

What is Rett syndrome?

Rett syndrome is a neurodevelopmental disorder which affects 1 in every 10,000 to 15,000 young girls.  The cause of this disease is a dominant defect in the X chromosome.  Typically, after about 6 to 18 months of nearly normal development, young girls with Rett syndrome experience a slow regression in motor skills and mental abilities.  Of note, apraxia or the inability to perform motor functions including body movements, eye movements and speech is a most disabling aspect of this condition.  Moreover, Rett syndrome also causes hand-wringing behaviors and autism-like symptoms.  Please note that although some people with Rett syndrome have autism spectrum disorder (ASD), too, Rett syndrome is distinct from ASD.

Although the initial onset of Rett syndrome is associated with the most profound loss, in many people, symptoms plateau with some eventual improvement in cognition and communication skills.  Although many young women with Rett syndrome survive through adulthood with relative good quality of life, breathing problems, digestion problems, spinal curvature and seizures are common. Contrary to what some may believe, many people with Rett syndrome can and do walk.

Of particular note, the symptoms, clinical course and quality of life of those with Rett syndrome is highly variable.

A longitudinal look at Rett syndrome

In a 2014 article titled “Twenty years of surveillance in Rett syndrome: what does this tell us?,” Australian researchers detail findings from an-up-to-20-year look at Rett syndrome.  Specifically, researchers analyzed epilepsy; musculoskeletal, gastrointestinal, autonomic dysfunction; and behavior of individuals aged 18 years and older. Here are some of their eye-opening findings:

  • Survival was 77.6 percent at 20 years.
  • Survival was 71.5 percent at 25 years.
  • Survival was 59.8 percent at 37 years.
  • The majority of participants lived with their parents (71 percent) with the rest living in long-term care facilities.
  • A combined 61 percent of participants walked either unaided or with assistance.  Of note, this statistic may represent selection bias with participants who could walk having milder cases of Rett syndrome.
  • Nearly two-thirds of adult women with Rett syndrome took epilepsy medications, and a third of these women had seizures that were refractory to medication.
  • Sixty-three percent of participants experienced sleep disturbances.
  • The majority of research participants had scoliosis (86 percent) with 40 percent having received surgery for the condition.  Fortunately, surgery was generally well tolerated among participants.
  • Anxiety and behavioral difficulties affected only a small proportion of research participants; nevertheless, researchers emphasize a need to better understand such psychiatric issues in women with Rett syndrome.
  • Bloating and constipation were experienced in 83 percent and 53 percent of participants respectively.  Additionally, many of the research participants had a gastrostomy feeding tube placed in order to improve fluid and food intake, prevent aspiration and relieve bloating.
  • Unusual breathing patterns including breath holding and hyperventilation were common among participants.
  • Urinary tract infections, pneumonia and other types of respiratory disease were common among research participants.

It should be noted that researchers also examined symptoms of Rett syndrome according to mutation type.  Their findings underscore the importance of diagnostic genetic testing in people with Rett syndrome.

Overall, the results of this longitudinal study are encouraging and fortunately suggest that many young girls with Rett syndrome go on to experience better quality of life than some might expect.  Moreover, the results concur with other studies on the disease. 

Researchers point out that further research is needed with special attention paid to how irregular breathing patterns impact survival, and how mood and anxiety inform care strategies.  Furthermore, researchers suggest that clinical care supervisors should closely monitor patient respiratory and gastrointestinal function.   

On a personal note, I want to commend researchers for a study well done.  This study represents the largest longitudinal study of its kind and a paragon among studies done on rare disease.  Too often, various facets of rare disease are left unstudied despite the reality that many people and families must live with such conditions.   

Selected Sources

Article titled “Twenty years of surveillance in Rett syndrome: what does this tell us?” by A Anderson and co-authors from Orphanet Journal of Rare Diseases published in 2014.  Accessed on 1/20/2015.

Ropper AH, Samuels MA, Klein JP. Chapter 38. Developmental Diseases of the Nervous System. In: Ropper AH, Samuels MA, Klein JP. eds. Adams & Victor's Principles of Neurology, 10e. New York, NY: McGraw-Hill; 2014. Accessed 3/3/2015.

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