Rett Patients With Milder Mutation Have Poorest Quality of Life, Study Finds

Girls and women with Rett syndrome caused by a mutation usually associated with milder disease have the poorest quality of life, according to a large study.

Data from this and previous studies suggest that such patients experience behavioral problems, including sleep disturbances, that profoundly affect quality of life.

The findings show, for the first time, that the type of mutation underlying Rett syndrome has important implications for patients’ quality of life, supporting its consideration when making decisions regarding disease management and patient support.

The study, “Determinants of quality of life in Rett syndrome: new findings on associations with genotype,” was published in the Journal of Medical Genetics.

Rett syndrome, which is most commonly caused by mutations in the MECP2 gene, can lead to a broad range of symptoms that are closely linked to the underlying genetic background, or genotype.

Some mutations, including p.Arg294, have been associated with milder symptoms than others, and people with such mutations generally have better functional outcomes, such as mobility and use of their hands.

Several studies have highlighted the multiple impacts of Rett syndrome on the quality of life of patients and their families.

Here, researchers at the Telethon Kids Institute of The University of Western Australia, set out to evaluate the potential association of genotype, age, functional abilities, and health with quality of life in Rett syndrome patients.

English-speaking families of 232 people with a confirmed Rett-causing MECP2 mutation were recruited from the International Rett Syndrome Database, which collects information about children and adults with Rett syndrome of any age from around the world.

They were asked to complete several questionnaires about sociodemographic factors (parental employment and education), parental health — with the 12-item Short Form Health Survey — and patients’ walking and feeding abilities, health (using the Sleep Disorder Scale for Children and Rett Syndrome Behavior Questionnaire), and quality of life, through the Quality of Life Inventory-Disability.

Notably, the Quality of Life Inventory-Disability is a validated parent-reported measure for children and adults with Rett that comprises six domains: physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors, and independence.

The study included a total of 210 patients whose parents completed all questionnaires and for whom full mutation details were available. Their median age was 18 years and 2 months (range 6 to 51 years) and most (94.8%) lived with their parents. Questionnaires were completed mostly by their natural mothers (87.1%).

Results showed that while the p.Arg294 mutation is considered a clinically milder genotype, girls and women with such mutation tended to have the poorest quality of life overall and in each of the domains. These findings were consistent with a previous U.S. study showing that patients with the p.Arg294 mutation had the lowest psychosocial score of health-related quality of life.

Also, data from this and other studies suggest that “in contrast to the apparently mild clinical severity, there is a [behavioral feature] which includes sleep disturbance that is associated with poor [quality of life] for those with the p.Arg294* mutation,” the researchers wrote.

In addition, quality of life appeared to drop with age, as patients older than 12 had poorer quality of life than younger participants. Patients able to walk or eat orally had better scores compared with those who could not, which is consistent with previous findings.

Better quality of life in most domains also was reported among patients without an epilepsy diagnosis or with a lower seizure frequency. More severe sleep disturbances and behavioral problems were associated with poorer quality of life.

Also, higher mental well-being scores in parents were linked to small increases in patients’ quality of life in some domains.

“These findings suggest that genotype, functioning and health each have implications for quality of life and should be considered when counselling families and planning clinical and support management strategies,” the team concluded.