Growth in Prader-Willi syndrome: Anthropometric patterns and analysis

Abstract

Prader-Willi syndrome (PWS) is a complex genetic disorder due to errors in genomic imprinting, generally from a paternal deletion of the chromosome 15q11-q13 region consisting of approximately 6 million DNA base pairs and a large cluster of imprinted genes. Maternal disomy 15 (both 15s from the mother) is the second most common form of PWS followed by an imprinting defect accounting for less than 3% of cases. PWS generally occurs sporadically and is characterized by infantile hypotonia, a poor suck, hypogenitalism/hypogonadism, mental deficiency and behavioral problems, hyperphagia leading to early childhood obesity, short stature due to growth hormone deficiency, small hands and feet, and a characteristic facial appearance with a narrow forehead, almond-shaped eyes, and sticky saliva. PWS is the most common genetic cause of life-threatening obesity with an estimated prevalence of 1 in 10,000-25,000 individuals. Obesity in PWS is due to hyperphagia, decreased physical activity, reduced metabolism, and an inability to vomit. However, energy expenditure is affected by body composition with PWS individuals having a lower muscle mass compared with controls and therefore reduced energy expenditure. Most children with PWS are born with a normal weight and height, but due to hypotonia and a poor suck, failure-to-thrive develops. By 2-4 years of age, they begin to overeat and develop a rapid weight gain. The fat mass in PWS subjects increases more rapidly than muscle mass or stature. Overall, the body fat may be greater than 50% if caloric intake is not controlled; however, sex reversal fat patterns are seen with males having greater subcutaneous fat compared with females even at an early age. Short stature in PWS is more related to shorter lower body segment compared with upper body in both sexes. Small hands and feet are common, but more remarkable in females. A narrow forehead and dolichocephaly are also common. Growth hormone treatment in PWS at all ages has led to a decrease in body weight and fat, an increase in muscle mass and physical activity, increased bone density, improved stature and greater self-esteem in children, and a higher quality of life. Heritability estimates indicate that taller than average parents will produce a taller than average child with PWS. Standardized growth curves have been published for common anthropometric parameters for the USA, German, and Japanese individuals with PWS and are useful when comparing with others and assist in healthcare and supervision.