Genetics of Prader-Willi syndrome and Prader-Will-Like syndrome

Abstract

The Prader-Willi syndrome (PWS) is a human imprinting disorder resulting from genomic alterations that inactivate imprinted, paternally expressed genes in human chromosome region 15q11-q13. This genetic condition appears to be a contiguous gene syndrome caused by the loss of at least 2 of a number of genes expressed exclusively from the paternal allele, including SNRPN, MKRN3, MAGEL2, NDN and several snoRNAs, but it is not yet well known which specific genes in this region are associated with this syndrome. Prader-Will-Like syndrome (PWLS) share features of the PWS phenotype and the gene functions disrupted in PWLS are likely to lie in genetic pathways that are important for the development of PWS phenotype. However, the genetic basis of these rare disorders differs and the absence of a correct diagnosis may worsen the prognosis of these individuals due to the endocrine-metabolic malfunctioning associated with the PWS. Therefore, clinicians face a challenge in determining when to request the specific molecular test used to identify patients with classical PWS because the signs and symptoms of PWS are common to other syndromes such as PWLS. This review aims to provide an overview of current knowledge relating to the genetics of PWS and PWLS, with an emphasis on identification of patients that may benefit from further investigation and genetic screening.

Keywords: Genetic screening; Imprinting disorder; Prader-Willi syndrome; Prader-Willi-like syndrome.

Fig. 1. Ideogram of chromosome 15q11-q13 showing genes located in the typical deletion region of Prader-Willi syndrome. BP, breakpoint; PWS-IC, Prader-Willi syndrome-imprinting center; AS, Angelman syndrome.

Fig. 2. Diagnostic algorithm in patients suspected of Prader-Willi syndrome (PWS). FISH, fluorescence in situ hybridization; CMA, chromosomal microarray; UPD, uniparental disomy; IC, imprinting center; MLPA, multiplex ligation probe amplification.