Shorter Telomeres and Faster Telomere Attrition in Individuals With Five Syndromic Forms of Intellectual Disability: A Systematic Review and Meta-Analysis

Background: People with intellectual disability suffer complex challenges due to adaptive functioning limitations, high rates of chronic diseases and shortened lifespans compared with the general population. Telomere shortening is a hallmark of ageing, and short telomeres are linked to neurological disorders. The main objective of this systematic review and meta-analysis was to identify any differences in telomere length and the rate of telomere attrition in leukocytes and fibroblasts from people with intellectual disability and controls.

Methods: PubMed, Scopus and ScienceDirect were searched. Articles that compared telomere length in individuals with intellectual disability to apparently healthy age-matched controls were included. Risk of bias was assessed using the AXIS tool and data were analysed using CMA.

Results: Fifteen studies comprised of 17 comparisons provided data and were included in meta-analyses. Compared with healthy controls (N=481), people with intellectual disability (N=366) from a known genetic syndrome (Cri du chat, Down, Hoyeraal– Hreidarsson, Williams or Nicolaides–Baraitser) possessed shorter leukocyte telomeres (SMD: −0.853 [95% CI: −1.622 to −0.084], p=0.03). Similarly, relative to controls (N=16), people with syndromic intellectual disability (N=21) possessed shorter fibroblast telomeres (−1.389 [−2.179 to −0.599], p=0.001). Furthermore, people with syndromic forms of intellectual disability also demonstrated a faster rate (2.09-fold) of telomere shortening.

Conclusions: Consistent with epidemiological findings on mortality and morbidity risk, people with syndromic intellectual disability appear to undergo a faster rate of biological ageing compared to the general population. These findings emphasise the need for healthy ageing lifestyle (i.e., exercise and stress management) and therapeutic interventions for people with syndromic intellectual disability.