Prader Willi Syndrome (PWS) is a complex, multi-systemic genetic disorder with characteristic clinical features caused by a defect in chromosome 15. The prevalence of PWS is about 1:10,000 to 1: 30,000.
The diagnosis of PWS is based on clinical suspicion for the presence of a set of typical features and then confirmed with genetic testing. The major clinical features include: morbid obesity, hypotonia, hypogonadism, hyperphagia, developmental delay, and behavior concerns. Genetic testing with DNA methylation studies is confirmatory. FISH analysis may also be used for genetic testing as well.
The genetic defect is primarily due to the absence of or loss of activity of genes on chromosome 15 that are normally inherited from the father. This may occur in one of three ways: About 70% of cases have a deletion of the paternal chromosome 15, another 25% of PWS patients may be due to the presence of 2 copies of maternal chromosome 15 (maternal uniparental disomy) and no paternal chromosome 15, and about 5 % of patients may an imprinting disorder which causes the paternal chromosome 15 to be inactive. The exact cause of why a lack of the genes from chromosome 15 of the father results in the characteristic collection of findings seen in PWS is still not known.
Patients with PWS have characteristic features. Different clinical features may be noted at various ages. There may be suspicion during prenatal period with features of: decreased fetal movements and breech presentation. The birth weight and length may be low. The babies in the first few months of life are noted to have: low muscle tone, poor sucking, poor reflexes, weak cry, failure to thrive, may need NG/G- tube feeding, characteristic physical features (including narrowing of the skull at the temples, “almond-shaped” eyes, thin upper lip with some downturn to the corners of the mouth, and tapered fingers), strabismus, undescended testes/ small penis in boys. There is usually a degree of delayed motor development (typically sitting at 12 months and walking at 24 months). Language may also be delayed. There is often mild to moderate intellectual disability and a characteristic behavior profile.
Often by about 4 years of age, there is an uncontrolled increase in appetite that generally results in significant excessive weight gain and obesity. Obesity, developmental delay, learning disabilities, speech delay, and behavior concerns (including skin picking), continue into adolescence and adulthood. Growth hormone deficiency is common and growth hormone treatment is recommended in PWS patients. Other concerns seen include: delayed puberty, low bone mineral density, disordered sleep, and scoliosis.
There is no cure for PWS at this time. Presently, treatment is directed towards addressing their medical concerns. Comprehensive management of the multiple systemic concerns seen in PWS patients is ideally best addressed in a multidisciplinary clinic, such as the one we have here at Nationwide Children’s Hospital. Consistent specialists from several departments are involved in the care of these individuals and have expertise in dealing with the particular issues faced by PWS patient and their families. Endocrine disorders are routinely screened for and hormone replacement therapy is given for any hormonal deficiencies noted. Growth hormone therapy in particular is very helpful in improving their muscle mass and muscle strength. Occupational therapy, physical therapy, and speech therapy are valuable to promote motor development. Psychology therapy is valuable to minimize behavior challenges. Feeding concerns including the failure to thrive in infancy and obesity in later childhood need close supervision by a dietitian; many patients need a “G-tube” feeding tube to optimize nutrition in infancy followed by methods for dietary restriction in older children including: structured mealtimes and lack of access to food between meals. Complications of obesity and sleep apnea are addressed aggressively as well.
Research is being conducted on the genes that are involved in causing PWS with the hope of an eventual gene therapy to cure the condition. Presently, the aim is to address the complex, multi-systemic medical needs of these patients in a comprehensive and effective manner to improve their overall health and quality of life.