Prader-Willi Syndrome

The major features of this multisystem disorder include prenatal and neonatal central hypotonia causing poor suck and infantile failure to thrive, characteristic facial appearance, developmental delay/generally mild mental retardation, childhood-onset obesity, short stature for the family, hypogonadism causing genital hypoplasia and pubertal insufficiency, and a characteristic behavior disorder. Obesity-related complications are the major cause of morbidity and mortality. The cause of Prader-Willi syndrome is absence of paternal contribution at chromosome 15q11-13, a region involving genomic imprinting, through deletion, maternal uniparental disomy, or an imprinting defect. The specific genes involved are not yet definitively delineated. Clinical diagnostic criteria for Prader-Willi syndrome have been published, but confirmation requires diagnostic testing, which is clinically available. Management is mostly supportive since no definitive treatment is known. Special feeding techniques are usually required to avoid or treat failure to thrive in infancy. Early infant stimulation followed by special educational resources can optimize developmental outcome. Obesity can be avoided or treated through appropriate nutrition, exercise, and environmental controls. Growth deficiency and abnormal body composition (high fat:lean body mass) respond well to growth hormone replacement. Sex hormones can be given to replace the deficient ones. Behavioral problems are treated through parenting skill enhancement, behavior modification, or psychotropic medication. Treatment of abnormal saliva secretion and sleep disturbance are also possible. Keywords: Prader-Willi syndrome; hypotonia; obesity; hypogonadism; failure to thrive; growth hormone deficiency; mental retardation; developmental delay; dysmorphic features; sleep disturbance; diagnostic criteria; imprinting; deletion; chromosome 15; uniparental disomy