People with Prader–Willi syndrome (PWS) who received growth hormone therapy had significantly higher vocabulary IQ scores compared with those who did not have the treatment, a study shows.
The study also revealed that PWS patients whose disease is caused by maternal uniparental disomy — in which two copies of chromosome 15 come from the mother — showed long-term stabilization of vocabulary with age.
Prader-Willi syndrome is a genetic disorder caused by the loss of function of specific genes on chromosome 15. There are three genetic subtypes associated with PWS. The most common is due to the deletion of genes from the father on chromosome 15, known as 15q11-q13 deletion. The second most common, called maternal uniparental disomy (UPD), is caused by the presence of two copies of chromosome 15 from the mother. Remaining cases involve other chromosomal 15 abnormalities.
Cognitive impairment and weight gain due to excessive overeating (hyperphagia) are two common features of PWS. Another hallmark is short stature — and one treatment is growth hormone (GH) therapy.
While GH therapy is the standard of care for PWS patients, there is limited evidence regarding its benefits on cognition, or intelligence.
Researchers, therefore, decided to compare the effectiveness of GH therapy on intelligence and body mass index (BMI) in patients with different PWS subtypes.
They analyzed clinical, genetic, and cognitive data from 103 people with PWS from two different groups (or cohorts). Among them were 56 patients from the University of California, Irvine (UCI), and 47 from Vanderbilt University in Tennessee. All patients had been previously diagnosed and treated. Some received GH therapy, while others did not.
In the UCI group, which included 11 adults and 45 children, the mean age was 11.6 years (range between 3 and 38 years). There were 31 people with chromosome deletions, and 25 with the UPD subtype. Over a five-year period, 30 patients received GH, while 26 never received GH therapy.
Stanford Binet intelligence tests were used in this patient group to evaluate cognitive ability. These included subtests that assessed vocabulary, pattern analysis, quantitative skills, and bead memory. A composite score represented the sum of the subtests’ scores.
The Vanderbilt group was older, with a mean age of 22.64 years (range between 10 to 44 years), and included 33 adults and 14 children. Chromosomal deletions accounted for 26 patients, while 21 had the UPD subtype. In this group, only two patients received GH therapy.
The Wechsler (WAIS-R for adults; WISC-III for children) IQ tests were used in this group to assess intelligence. These tests measure three scoring indexes: verbal, performance, and full-scale IQ.
Analysis of the UCI group revealed there was no correlation between total composite Stanford Binet scores and most subtest IQ scores, regardless of whether patients had GH therapy or not. However, significantly higher IQ scores were found in the vocabulary subsection of the Stanford Binet test in the GH-treated group (44.03) when compared with those who were not treated with GH (37.52). This suggests that GH therapy improved intelligence in some PWS patients.
There also was no significant difference identified in the UCI group in total IQ scores in individuals with the deletion compared to UPD subtype. However, the analysis showed that GH therapy in the UPD subtype resulted in less decline with age in composite and vocabulary IQ scores.
As there were only two patients treated with GH in the Vanderbilt group, researchers were unable to properly evaluate the effects of growth hormone therapy. However, the analysis of patients within this group found significantly higher verbal IQ scores in the UPD versus deletion subtype groups, with better development of verbal than spatial skills.
For BMI, no differences were found between the deletion and UPD subtypes.
Overall, the team concluded that “medical care and response to treatment with growth hormone may influence intelligence impacted by PWS genetic subtypes and possibly age.”
The investigators emphasized that more research is needed.
“Additional studies are needed to support the relationship between GH treatment and intelligence in PWS. Length and onset of GH treatment with its impact on IQ over time influenced by PWS genetic subtypes (UPD 15 vs. deletion) will require more investigation,” they said.