Prader-willi syndrome: clinical aspects

Abstract

Prader-Willi Syndrome (PWS) is a complex multisystem genetic disorder that shows great variability, with changing clinical features during a patient's life. The syndrome is due to the loss of expression of several genes encoded on the proximal long arm of chromosome 15 (15q11.2-q13). The complex phenotype is most probably caused by a hypothalamic dysfunction that is responsible for hormonal dysfunctions and for absence of the sense of satiety. For this reason a Prader-Willi (PW) child develops hyperphagia during the initial stage of infancy that can lead to obesity and its complications. During infancy many PW child display a range of behavioural problems that become more noticeable in adolescence and adulthood and interfere mostly with quality of life. Early diagnosis of PWS is important for effective long-term management, and a precocious multidisciplinary approach is fundamental to improve quality of life, prevent complications, and prolong life expectancy.

Figure 1

Schematic representation of the region 15q11.2-q13. The Prader-Willi syndrome (PWS) region is shown in violet, and Angelman syndrome (AS) region is shown in green. The red arrows indicate the three deletion breakpoints common to PWS and AS (BP1, BP2, and BP3). On rare occasions, there will be a distal breakpoint at BP4 or BP5. Type-1 deletions (T1D) extend from BP1 to BP3, and type-2 deletions (T2D) extend from BP2 to BP3.

Figure 2

Algorithm for genetic testing for PWS. MS-MPLA: methylation-specific-multiplex ligation-dependent probe amplification analysis. UPD: uniparental disomy. IC: imprinting centre.

Figure 3

Standard BMI proposed by WHO from 0 to 2 years.