Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Prader-Willi Syndrome (PWS) [Q87.1]

OMIM number: 176270

Dr. med. Imma Rost

Scientific Background

The Prader-Willi syndrome (PWS) is marked by a severe muscular hypotonia with poor feeding and failure to thrive during infancy. During pregnancy, less foetal movements may be observed; birth may involve a breech presentation. Motor development is moderately delayed; usually the children are able to sit at the age of one and are able to walk at the age of two. There is a moderate intellectual disability; in approx. 40% the intelligence is within the lower norm; yet, learning difficulties frequently occur. After infancy, hyperphagia with development of adipositas occur, followed by complications such as diabetes mellitus and cardiopulmonary disorders. Short stature is common. Hypogenitalism or hypogonadism with low hormone levels is observed; pubertal development is not according to age. Typical behaviour is stubbornness and temper tantrums as well as skin picking with a tendency to self-injury. PWS patients show good visual observation and processing skills, such as assembling jigsaw puzzles. Physical features frequently include a narrow face, almond-shaped eyes, strabismus, a small mouth with thin upper lip, small hands and feet. Most patients with PWS caused by a microdeletion show hypopigmentation. The frequency is 1 in 15,000 to 1 in 30,000. The causative genes of the Prader-Willi and the Angelman syndrome are located in a chromosomal region (15q11.2-q13) which is subject to what is known as genomic imprinting. This parent-specific imprinting causes the genes to differ in the degree of DNA methylation, the chromatin structure and therefore in the expression, depending on what parent they are originating from. It is controlled by an imprinting center in 15q11.2-q13, consisting of two parts. Due to this special feature, PWS and AS may have other causes, besides the microdeletion, that lead to loss of expression of the affected genes. Several genes in the region 15q11.2-q13 are only expressed by the paternal chromosome 15 and are associated with causing PWS. Approx. 70% of all PWS patients exhibit a microdeletion 15q11.2-q13 on the chromosome 15 inherited from the father. Approximately 30% have a maternal uniparental disomy 15 (UPD), meaning both chromosomes 15 originate from the mother, none from the father. Approx. 1% exhibit a defect in the imprinting center; in a few patients, a chromosomal structural aberration including the region 15q11.2 was found. There are certain genotype-phenotype correlations. The molecular/cytogenetic (FISH) analysis detects only the microdeletion, the methylation-sensitive PCR detects microdeletion, UPD and imprinting mutation without specification.