Development and Manifestations of Prader-Willi Syndrome - Research Paper Example

Development And Manifestations Of Prader-Willi Syndrome e Introduction Prader-Willi Syndrome (PWS) is a disorder caused by DNA abnormalities of chromosome 15. The incidence of PWS is one in eight thousand births in the United States. Though the onset of the condition occurs at birth, the symptoms begin by one to four years of age (Escott-Stump: 191). Other authors believe that the commonly prevalent syndrome may have an incidence of 1/15,000 to 1/30,000. Early diagnosis is essential for effective long term treatment and management of Prader-Willi Syndrome which affects multiple systems. It is a sporadic disorder with a recognizable pattern of dysmorphic features along with predominant “neurologic, cognitive, endocrine and behavioral/ psychiatric disturbances” (Cassidy & Driscoll: 3). Thesis Statement: The purpose of this paper is to investigate Prader-Willi Syndrome: the disease, who discovered it, phases of the syndrome, causes, symptoms and cures. Discussion Prader-Willi Syndrome (PWS) was the first recognized human disorder related to genomic imprinting and the first shown to be caused by uniparental disomy. Failure of expression of paternally inherited genes in the PWS region of chromosome 15 leads to the manifestation of the syndrome. The genetic condition can occur by three main mechanisms which lead to absence of expression of paternally inherited genes in the 15q11.2-q13 region: “paternal microdeletion, maternal uniparental disomy, and imprinting defect” (Cassidy & Driscoll: 3). According to Cassidy & Driscoll (pp.11-12), though it has been twenty-seven years since the genetic region responsible for PWS was first identified, the precise gene(s) responsible for the phenotype is still not known. Recent data has signified the HBII-85 snoRNA gene, 48,73 as playing a key role, and the authors state that the near future should reveal its gene targets, by which treatments may be developed. Identification of the responsible gene(s) would also help in indicating the causes of obesity, hypogonadism, other hypothalamic deficiencies, psychosis, and autism in the general population. PWS has already helped to disclose a great deal about imprinting, and there is hope that it will have more to teach researchers and scholars. Discovery According to Whittington & Holland (p.5), in 1956 the Swiss pediatricians Prader, Labhart and Willi first described a group of children with what subsequently came to be called PWS. At that time, the main characteristics that were noted were: neonatal hypotonia, impaired sexual development, short stature, a tendency for severe obesity, learning disabilities and mental retardation. As more people were identified with the syndrome all over the world the common characteristics were identified with increasing accuracy, and advances were made in distinguishing PWS from other conditions with similar features. Phases of the Syndrome There are two distinct developmental phases of Prader-Willi Syndrome. The first phase is during infancy, when there is hypotonia, feeding and sucking problems, and failure to meet developmental milestones. In complete contrast to this “failure to thrive” period, the second phase begins between two and six years of age, and is characterized by “hyperphagia, food preoccupations, and food seeking” (Mash & Barkley: 509). Further, young children are typically friendly, pleasant and affectionate. Though these features may not necessarily disappear, the beginning of hyperphagia marks the onset of maladaptive behaviors such as temper tantrums and food stealing. These may diminish with age; though adults with the syndrome sometimes manifest mood disorders, psychosis, thought disturbance and heightened vulnerabities. Causes Prader-Willi syndrome is an example of a genetic condition involving genomic imprinting. The three main genetic causes are: 5-7Mb deletion of the paternally inherited chromosomal 15q11.2-q13 region, maternal uniparental disomy 15, and a defect in the imprinting process in the 15q11.2-q13 region on the paternally inherited chromosome. Sometimes chromosomal translocation leads to deletion. A number of imprinted genes have been mapped to the PWS region of 15q11.2-q13, but their role in most aspects of the phenotype is not well understood (Cassidy & Driscoll: 3). Symptoms The distinctive features of the condition among infants are: absence of crying, poor suck, lethargy, infant hypotonia or poor muscle tone, and hypogonadism or retardation of sexual growth and development. Among young children there is delay in motor development, learning disability, mental retardation with average IQ around 70, small hands and feet, atypical facial features, and obesity because of insatiable appetite or hyperphagia in early childhood. From childhood, short stature is part of the syndrome and is not the outcome of nutritional deficiency. Increased fasting ghrelin levels occur in most cases. There is absence of gag reflex or vomiting, and patients may eat contaminated or inedible food combinations (Dykens: 163). According to Cassidy & Driscoll (3-4, 6), there is a distinctive body habitus. The facial phenotype of PWS in adolescence and adulthood includes a narrow bifrontal diameter, almond-shaped and slightly up-tilted eyes, narrow nasal bridge, and thin upper lip. The typical behavioral phenotype which begins in early childhood includes temper tantrums and compulsive traits such as repeated organizing, need to finish one thing before engaging in another activity, difficulty with change of routine, stubbornness, and controlling and manipulative behavior. Several of the behavioral characteristics are the same as those of autism spectrum disorder, which is diagnosed in up to 25% of the individuals. Attention deficit, hyperactivity symptoms and “insistence on sameness are common and of early onset” (Cassidy & Driscoll: 5). The severity of behavioral problems increases with age and body mass index, and then declines in older adults. In 5 to 10% of the individuals, psychosis is evident by young adulthood. Those suffering from PWS are also prone to osteoporosis, Type 2 diabetes mellitus, respiratory disorders, and cardio-respiratory failure related to obesity and hypotonia. Since sexual development is incomplete, most PWS individuals are infertile (Allen & Carrel: 1297S). Treatment General Objectives Management of the syndrome is symptomatic and supportive, focusing on “control of food intake, hormone replacement therapies, special education and sheltered employment, and behavior management”, state Cassidy & Driscoll (p.4). This is supported by Escott-Slump (p.191) who adds that management includes weight reduction and the monitoring of weight weekly. An exercise program is essential, for weight reduction to take place In preschool children obesity should be prevented. It is essential to maintain recommended dietary intakes for all nutrients and protein to promote growth and development. Feeding assistance should be provided if required. Unusual food seeking behaviours such as eating food from the trash, eating inappropriate or unpalatable food combinations should be minimized. Similarly, pica or craving and compulsive eating of non-food substances and related nutritional deficiencies should be corrected. Complications such as coronary heart disease, hypertension, diabetes mellitus, sleep apnea, dental problems, and pneumonia should be prevented. If serum lipid levels are elevated, they have to be appropriately corrected (Escott-Stump: 191). There is evidence that treatment with growth hormone (GH) results in increased height velocity in children with PWS, decreased weight for height index values and body fat mass, and have a positive effect on lean body mass, at least during the first year of therapy. Biliopancreatic diversion alone is not an adequate treatment for weight loss. Behavioral manifestations including poor appetite control and cognitive limitations require long-term multidisciplinary management. (Eiholzer & Whitman: 1153). It is necessary to help reduce guilt and depression; and to promote self-monitoring which should be the ultimate goal (Escott-Stump: 193). Food and Nutrition Frequently, children with Prader-Willi syndrome start with failure to thrive (FTT), and then become overweight; hence, it is important to identify where the child is in this continuum. A low calorie diet should be used for weight reduction. Patients’ needs are about 60% of those without PWS. It should be ensured that the diet provides adequate protein and nutrients. Recommended dietary allowances according to age need to be followed, while at the same time overall fat and energy intake need to be reduced (Escott-Stump: 191). Conclusion This paper has highlighted Prader-Willi Syndrome: the disease, the researchers who discovered it, phases of the syndrome, causes, symptoms and multidimensional treatments. The precise gene responsible for the phenotypes is still not known. However, it is hoped that the near future should disclose the gene targets of the HBII-85 snoRNA gene, 48,73 recently identified as playing a key role; from which highly effective treatments may be successfully developed. Works Cited Allen, D.B. & Carrel, A.L. Growth hormone therapy for Prader-Willi syndrome: a critical appraisal. Journal of Pediatric Endocrinology & Metabolism. S17 (2004): 1297S. Cassidy, S.B. & Driscoll, D.J. Prader-Willi syndrome. European Journal of Human Genetics. 17 (2009): 3-13. Dykens, E. Contaminated and unusual food combinations: what do people with Prader-Willi syndrome choose? Ment Retard, 38 (2000): 163. Eiholzer, U. & Whitman, B.Y. A comprehensive team approach to the management of patients with Prader-Willi syndrome. Journal of Pediatric Endocrinology & Metabolism, 17 (2004): 1153. Escott-Stump, Sylvia. Nutrition and diagnosis-related care. Edition 6. Maryland: Lippincott Williams & Wilkins. (2007). Mash, Eric J. & Barkley, Russell A. Child psychopathology. Edition 2. New York: Guilford Press. (2003). Whittington, Joyce & Holland, Tony. Prader-Willi syndrome: development and manifestations. The United Kingdom: Cambridge University Press. (2004). Read More