Prader-Willi syndrome (PWS) is characterized by severe muscle hypotonia with drinking difficulties and failure to thrive in infancy. During pregnancy, decreased fetal movements may be evident and delivery may occur out of breech presentation. Motor development is moderately delayed meaning children can sit on average at one year of age and walk freely at two years of age. There is a mild mental retardation with approximately 40% of children having intelligence in the lower normal range. Nevertheless, learning difficulties are common. Beyond infancy, hyperphagia occurs with development of obesity and subsequent complications such as diabetes mellitus and cardiopulmonary disease. In most cases, short stature develops. Hypogenitalism or hypogonadism with low hormone levels is present and pubertal development is often not age-appropriate. Stubbornness and temper tantrums are observed as typical behavior patterns, as well as skin picking with a tendency to self-injury. Patients of Prader-Willi syndrome have good visual comprehension and processing skills, e.g. putting puzzles together. External features often include a narrow face, almond-shaped eyes, strabismus, a small mouth with a narrow upper lip, and small hands and feet.
Most patients having a microdeletion as the cause of Prader-Willi syndrome have some degree of hypopigmentation. The incidence is reported to be 1:15,000 to 1:30,000. The disease-causing genes in Prader-Willi syndrome (and Angelman syndrome) are located in a chromosomal region (15q11.2-q13) that is susceptible to so-called genomic imprinting. This parental imprinting causes genes to vary in the level of DNA methylation, chromatin structure, and thus expression, depending on which parent they are derived from. This is controlled by a two-part imprinting center in 15q11.2-q13. Because of this unique feature, Prader-Willi syndrome and Angelman syndrome may have other causes besides microdeletion that lead to loss of expression of the affected genes. Several genes in the region 15q11.2-q13 are expressed only from paternal chromosome 15 and are causally related to Prader-Willi syndrome. Approximately 70% of PWS patients have a microdeletion 15q11.2-q13 on the chromosome 15 inherited from the father. About 30% have a maternal uniparental disomy 15 (UPD), i.e. both chromosomes 15 originate from the mother and none from the father. About 1% have a disorder in the imprinting center, and in a few cases a chromosomal structural aberration involving the region 15q11.2-q13 was found.
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