Eating Behaviour in Prader-Willi SyndromeThursday, April 7, 2011
As blogged before, Prader-Willi syndrome (PWS) is the most common syndromal cause of obesity, with an estimated prevalence of about 1 in 25,000. It is an autosomal dominant disorder characterized by diminished fetal activity, obesity, hypotonia, mental retardation, short stature, hypogonadotropic hypogonadism, and small hands and feet.
PWS was the first syndrome attributed to genetic ‘imprinting’ and occurs when seven genes (or some subset thereof) on chromosome 15 (q 11-13) are deleted or unexpressed (chromosome 15q partial deletion) on the paternal chromosome (with concomitant ‘silencing’ of the maternal chromosome).
Although hyperphagia is a dominant feature in PWS, eating behaviour appears to be more complex than simply being born with a voracious appetite.
In fact, as extensively reviewed by Miller and colleagues from the University of Florida in a paper just published in the American Journal of Medical Genetics, ingestive behaviour in individuals with Prader-Willi sydrome appears to progress in three and sometimes four distinct phases.
Based on the longitudinal follow-up of a large number of PWS patients, the authors characterize the growth, metabolic, and laboratory changes associated with seven different nutritional phases, with five main phases and two sub-phases each in phases 1 and 2.
Phase 0 occurs in utero, with decreased fetal movements and growth restriction compared to unaffected siblings.
In phase 1 the infant is hypotonic and not obese, with sub-phase 1a characterized by difficulty feeding with or without failure to thrive (ages birth-15 months; median age at completion: 9 months). This phase is followed by sub-phase 1b when the infant grows steadily along a growth curve and weight is increasing at a normal rate (median age of onset: 9 months; age quartiles 5-15 months).
Phase 2 is associated with weight gain-in sub-phase 2a the weight increases without a significant change in appetite or caloric intake (median age of onset 2.08 years; age quartiles 20-31 months;), while in sub-phase 2b the weight gain is associated with a concomitant increased interest in food (median age of onset: 4.5 years; quartiles 3-5.25 years).
Phase 3 is characterized by hyperphagia, typically accompanied by food-seeking and lack of satiety (median age of onset: 8 years; quartiles 5-13 years).
Phase 4 is seen in some adults when an individual who was previously in phase 3 no longer has an insatiable appetite and is able to feel full.
While the neurological and endocrine mechanisms underlying the progression of these phases remains unclear, the authors note that:
“Awareness of the various phases will aid researchers in unraveling the pathophysiology of each phase and provide a foundation for developing rational therapies.”
“Counseling parents of newly diagnosed infants with PWS as to what to expect with regard to these nutritional phases may help prevent or slow the early-onset of obesity in this syndrome.”
In case readers are wondering how this rather rare syndromal form of obesity may be relevant to the ‘big picture’, it may be important to point out that such rare forms of obesity provide unique insights into the complex biology of ingestive behaviour and energy regulation.
Elucidating the biological mechanisms underlying these rare genetic disorders can not only help better treat the affected individuals but may well lead to novel treatments even for individuals with the more common ‘garden variety’ forms of obesity.
As blogged before, such studies are now also well underway at the University of Alberta.
For more information on PWS please visit the website of the Foundation for Prader-Willi Research Canada.
Miller JL, Lynn CH, Driscoll DC, Goldstone AP, Gold JA, Kimonis V, Dykens E, Butler MG, Shuster JJ, & Driscoll DJ (2011). Nutritional phases in Prader-Willi syndrome. American journal of medical genetics. Part A PMID: 21465655