Introduction to Genetics of Prader Willi Syndrome

By | May 20, 2012


Many of the child behavior problems and cognitive capabilities can be explained within the framework of understanding the characteristic of Prader Willi Syndrome. Society, family and hereditary factors also influence it. PWS is a disease of altered growth and development. Affected persons are potentially overweight, sexually immature, and short and developmentally delayed individuals. The patient with PWS is usually mildly retarded, stubborn and emotionally labile, they rarely develop to cope with their insatiable hunger. Environmental restrictions are necessary for the patient to prevent the life threatening obesity. Although PWS is not a common disorder, the frequency of the disease is around 1:10000 – 1:25000. According to the Prader Willi Syndrome Association (USA) over 5000 cases have been identified throughout the world. It affects equally to the both sexes and it does not depend on specific race and socioeconomic classes or geographic regions. The unique disorder manifests abnormalities of growth, learning and physical developments which provide an understanding of issue like neurophysiology and behavior, patterns of genetic control of morphogenesis.


It was first described by a group of Swiss doctors A. prader, A. labhart and H. Willi in 1956. After the description of disease several cases had been reported with the same features. Although these author described an unusual pattern of other abnormalities like diminished fetal activity, profound poor muscle tone, feeding problem infancy, hypogonadism and hypogenitalism, short stature, small hands and feet, retarded bone, and delayed developmental milestone, characteristic faces, cognitive impairment, onset of gross obesity in early childhood and a tendency to develop diabetes in adolescence and adulthood. Later in 1963 they follow-up nine cases and elaborated on the role of diabetes mellitus and mental retardation in clinical picture (Prader, Cambhart & Willi, 1963).


Further landmark studies indicated orthopedic, dental, and development characteristics could assist that PWS has two clearly identifiable phases, which had been reported by Gablian and Royer (1968), Zellweger and Schneider (1968) and Dunn (1968). In 1972 hall and Smith gave detailed information of 32 PWS patient that supported the earlier diagnostic criteria as well as behavior and personality problems that appears to intensify with age. Medical problem associated with PWS have been discussed by Kriz and Clonniger (1981), Holm and Laurnen (1981), Bray, Dahms, Swerdloff et al. (1983) and Cassidy (1984). A study of 232 individual with PWS indicated that with appropriate nutritional control the life expectancy has been extended, that emotionally liability increases with age and is independent of the presence of the adult obesity, that psychosocial adaptation requires special management and that the presence of PWS has a profound impact on family life (Greenswag, 1987).


Advances in human genetics have spawned the research activity on PWS. The genetics of Prader Willi Syndrome are quite complicated; it can be caused by more than on type of genetic abnormality, but all results in an important piece of genetics coding being missed from the paternal chromosome. The most common genetic abnormality present in about 70% of the PWS patients is due to a deletion of a minute piece of chromosome 15 inherited from father and the rest of 25-30% of PWS are inherited from mother. In a few other cases, translocation and other rare anomalies occur, which are the only hereditary cases of PWS. It is widely thought that most of the genetic information missing from PWS patients affects the hypothalamus, which controls and regulates many of the hormones.


The diagnosis of PWS has improved in recent years, partly because of awareness on the part of doctors, but also because of chromosome tests are now done at a molecular level.