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Last updated: 7/12/2023
Years published: 1984, 1985, 1987, 1988, 1989, 1992, 1994, 1996, 1997, 1998, 1999, 2000, 2002, 2004, 2005, 2009, 2012, 2015, 2018, 2023
NORD gratefully acknowledges Merlin G. Butler, MD, PhD, Director, Division of Research and Genetics, Director, KUMC Genetics Clinic and Professor of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, for assistance in the preparation of this report.
Summary
Prader-Willi syndrome (PWS) is a genetic multisystem disorder characterized during infancy by lethargy, diminished muscle tone (hypotonia), a weak suck and feeding difficulties with poor weight gain and growth and other hormone deficiency. In childhood, features of this disorder include short stature, small genitals and an excessive appetite. Affected individuals do not feel satisfied after completing a meal (satiety). Without intervention, overeating can lead to onset of life-threatening obesity. The food compulsion requires constant supervision. Individuals with severe obesity may have an increased risk of cardiac insufficiency, sleep apnea, diabetes, respiratory problems and other serious conditions that can cause life-threatening complications. All individuals with PWS have some cognitive impairment that ranges from low normal intelligence with learning disabilities to mild to moderate intellectual disability. Behavioral problems are common and can include temper tantrums, obsessive/compulsive behavior and skin picking. Motor milestones and language development are often delayed. PWS occurs due to abnormalities affecting certain genes in the proximal long arm of chromosome 15 when deleted from the fatherโs chromosome 15 and hence referred to as a genomic imprinting disorder which depends on the sex of the parent donating the chromosome leading to the chromosome defect in the child. These abnormalities usually result from random (sporadic) errors in egg or sperm development but are sometimes inherited.
Introduction
Originally described in the medical literature in 1956, PWS is the first disorder confirmed to be due to imprinting errors (see Causes section). It is the most common genetic cause of life-threatening childhood obesity. The disorder was once known as hypogonadism, hypotonia, hypomentia, obesity (HHHO).
The symptoms and severity of PWS can vary from one person to another. Many features of the disorder are nonspecific, and others may develop slowly over time or can be subtle. It is important to note that affected individuals may not have all the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. Often this requires input from a clinical geneticist or genetic counselor with experience in this genetic disorder to supply the most recent and accurate information about the disorder and discuss genetic testing options or treatment plans.
Initially, infants will exhibit diminished muscle tone (hypotonia), which can cause a baby to feel โfloppyโ when held. Infantile hypotonia, which is often severe, is a near universal feature of the disorder. Hypotonia can be present before birth (prenatally) potentially causing decreased fetal movements and abnormal positioning of the fetus (e.g., breech position). Prenatal hypotonia is associated with an increased risk of requiring an assisted delivery. After birth, hypotonia is associated with lethargy, a weak cry, poor responsiveness to stimuli and poor reflexes including poor sucking ability, which result in feeding difficulties and failure to thrive. Infants are usually unable to breastfeed and may require tube feeding. Hypotonia slowly improves over time, but some adults with PWS may continue to have some degree of hypotonia.
Affected infants may also have distinctive facial features including almond-shaped eyes, a thin upper lip, a downturned mouth, a narrow bridge of the nose, a narrow forehead, and a disproportionately long, narrow head (dolichocephaly). Distinctive facial features can be noticeable shortly after birth or may develop slowly over time.
As affected infants grow older, their feeding and appetite will improve, and they will grow appropriately. Typically, between 2-4.5 years of age, their weight increases although there may not be a noticeable change in appetite or caloric intake. Between 4.5-8 years old, appetite and caloric intake usually increases, often thereafter developing a need to eat an extraordinarily large amount of food (hyperphagia) usually because they do not feel satisfied after completing a meal (satiety). In addition, there is a decreased calorie requirement in people with PWS due to low muscle, decreased metabolism and decreased physical activity if not treated with growth hormone replacement. Consequently, overeating, rapid weight gain, and morbid obesity occur if not controlled by others. Not all affected children will go through these stages.
If left uncontrolled and untreated, morbid obesity can develop, potentially leading to life-threatening heart and lung complications, diabetes, high blood pressure (hypertension), and to other serious complications. The compulsion to eat is so overwhelming that people with this disorder, if left unsupervised, may endanger themselves by eating harmful food such as spoiled food or garbage and excessive quantities, harmful to the stomach. Affected children may also exhibit unusual behaviors regarding food including hoarding and/or foraging for food, stealing food and stealing money to buy food.
Some affected individuals have developed serious, life-threatening gastrointestinal complications due to episodes of binge eating. Such complications can include severe bloating (gastric dilatation) with the development of a hole or tear in the intestinal wall (perforation) and tissue loss (necrosis). They are noted to have decreased gastric emptying and swallowing difficulties.
Children with PWS also have varying levels of cognitive impairment, ranging from borderline or low normal intelligence with learning disabilities to mild to moderate intellectual disability. The attainment of motor milestones (e.g., walking or sitting up) and language development are often delayed.
Affected children generally have sweet and loving personalities, but often develop distinct behavioral issues. Such issues can include temper tantrums, stubbornness, obsessive/compulsive behavior, manipulative behavior and skin picking, which can cause chronic open wounds, scarring and infection. In some patients, the behavior profile may be suggestive of autism. Psychosis occurs in approximately 10-20% of late adolescents and young adults. Evidence shows that the type of chromosome 15 abnormality may relate to certain learning and behavioral problems.
Hypogonadism is a common finding in PWS. Hypogonadism refers to inadequate function of the sex organs, the testes in males and the ovaries in females. The sex organs in affected individuals fail to produce sufficient sex hormones, which can result in underdeveloped sex organs, incomplete development at puberty, delayed onset of puberty, and infertility. Genital underdevelopment is evident at birth. Affected males may have a small penis, underdeveloped scrotum, and small testes. Failure of one or both testes to descend (cryptorchidism) is a common finding, as well. Affected females may have an abnormally small clitoris or labia minor. Absence of a menstrual cycle (primary amenorrhea) is common and in some females the initial menstrual period (menarche) may not occur until 30 years of age or older.
Individuals with PWS have growth hormone (GH) insufficiency, a condition characterized by the inadequate secretion of growth hormone from the anterior pituitary gland, a small gland located at the base of the brain that is responsible for the production of several hormones. Children may be significantly below average height based upon sex and age (short stature). GH deficiency affects both children and adults and the final adult height of affected individuals is shorter than unaffected family members. If GH treatment is prescribed at the time of diagnosis, often now during early infancy, then the results are positive with a decrease in the amount of fat seen in PWS patients, an increase in muscle mass and altered body composition. In addition, there is reported evidence of an earlier diagnosis in PWS which reduces the other medical problems (comorbidities) seen in people with this disorder. Hence, GH treatment beginning at an early age in PWS can improve stature and body composition including weight with near normalization of growth by 18 years of age based on PWS specific growth charts in comparison with normal growth charts.
Affected individuals may also have abnormally small hands and feet, side-to-side curvature of the spine (scoliosis) and, in approximately 10% of individuals, a malformed hip (hip dysplasia). Scoliosis can occur at any age including infancy, varies in severity and should be monitored. Sleep problems are common, including excessive daytime sleepiness, reduced rapid eye movement (REM) latency, disruption of the normal sleep cycle, and central and/or obstructive sleep apnea.
Some individuals may have lack of color (pigment) known as hypopigmentation affecting the hair, eyes and skin particularly in those with the chromosome 15q deletion seen in about 60% of those with PWS (discussed in Causes). They may appear fair-skinned compared to other family members. Nearsightedness (myopia) and misaligned eyes (strabismus) may also occur.
Affected individuals may also experience recurrent respiratory infections. Up to 25% of affected individuals may have an underactive thyroid gland (hypothyroidism). In addition, the rates of certain conditions are increased in individuals with PWS including fractures due to decreased bone density (osteopenia), altered temperature sensation, a high vomiting threshold and swelling (edema) and ulcerations of the legs, especially in obese adults. Some individuals may have reduced flow of saliva with abnormally thick, sticky saliva. Additional symptoms that can occur in affected individuals include a high pain threshold, a tendency to bruise easily without known cause and seizures.
Some individuals with PWS may develop central adrenal insufficiency (CAI), a condition characterized by deficiency of adrenocorticotropic hormone (ACTH). This hormone is produced by the pituitary gland. One of the main functions of ACTH is to stimulate the adrenal glands to produce cortisol, which helps to regulate blood sugar and the body to deal with stress. In some patients, CAI may only be detectable during periods of stress (e.g., during illness or injury). The exact percentage of affected individuals with CAI and its overall implications to individuals with PWS are not yet fully understood. Natural history causes of death and survival trends in PWS have recently been published and useful to gain knowledge and current understanding and diagnosis with comorbidities in order to better monitor the health status and prognosis of someone with PWS.
PWS occurs when the genes in a specific region of chromosome 15 are not present or do not function. This region of chromosome 15 is located at 15q11.2-q13 and has been designated the Prader-Will syndrome/Angelman syndrome region (PWS/AS). In individuals with PWS, the nonfunctioning PWS/AS region is always located on the number 15 chromosome inherited from the father.
Chromosomes, which are present in the nucleus of human cells, carry genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated as X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated โpโ and a long arm designated โqโ. Chromosomes are further sub-divided into many bands that are numbered. For example, โchromosome 15q11.2-q13โ refers to bands 11.2-13 on the long arm of chromosome 15. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The changes affecting the genes associated with PWS may involve changes in the structure of a gene (genetic factors) or changes in the function or expression of a gene (epigenetics). Three specific abnormalities are primarily associated with PWS โ chromosomal 15q11-q13 deletion, maternal uniparental disomy 15 or both chromosome 15s from the mother and genetic imprinting errors in the region controlling gene activity on chromosome 15.
PWS is associated with a specific process known as genetic imprinting. Normally, everyone has two copies of every gene โ one received from the father, and one received from the mother. In most people, both genes are โturned onโ or active. However, some genes are preferentially silenced or โturned offโ based upon which parent gave the gene to the child (genetic imprinting). Genetic imprinting is controlled by chemical switches through a process called methylation and other chemical changes at the DNA level. Proper genetic imprinting is necessary for normal development. Defective imprinting has been associated with several disorders including PWS.
Imprinted genes tend to cluster or group together on chromosomes. Several imprinted genes are found in a cluster on the long arm (q) of chromosome 15. The cluster contains a functional region known as an imprinting center that regulates activity of the imprinted genes in this region.
In most people with PWS (about 60%), the PWS/AS region of the fatherโs chromosome 15 is missing or deleted. This chromosomal deletion results from a random error in development and is not inherited (de novo deletion) and is not inherited. Thus, most cases of PWS occur sporadically and the risk of recurrence in another pregnancy is less than 1%.
Recent data shows that in about 35% of people with PWS, the affected person inherits two copies of chromosome 15 from the mother and no copy of the fatherโs chromosome 15 (referred to as maternal uniparental disomy). This type of genetic change also occurs because of a random error in development. In most cases, the risk of recurrence of uniparental disomy is estimated to be less than 1%.
In less than 5% of people with PWS, the PWS/AS region of the fatherโs chromosome 15 is present, but the genes do not work properly. This form of PWS is due to an abnormality in genes called the imprinting center and is sometimes due to a genetic change (e.g., microdeletion) that can be passed from one generation to the next at a high risk (up to 50%).
In a very small proportion of affected people, PWS has occurred due to a balanced translocation of chromosome 15. Translocations occur when portions of certain chromosomes break off and are rearranged, resulting in shifting of genetic (e.g., genes of the imprinting center) material and an altered set of chromosomes. If a chromosomal translocation is balanced (meaning that it consists of rearranged chromosomes without anything missing or extra), then it is usually harmless to the carrier. However, such a chromosomal rearrangement may be associated with an increased risk of abnormal chromosomal development in the carrierโs children depending on events that occur in the egg or sperm production.
Several imprinted genes have been mapped to the PWS/AS region of chromosome 15. However, the specific genes involved and their role in the development of the various symptoms of PWS are being characterized but not yet known. Many symptoms associated with PWS are believed to be due to malfunction of the hypothalamus, a gland in the brain that regulates hormone secretions and under genetic control. Hormones produced by the hypothalamus affect body temperature, hunger, moods, sex drive, sleep and thirst. The hypothalamus also influences the release of hormones from other glands, especially the pituitary gland, which regulates the release of certain hormones including growth and sex hormones.
PWS affects males and females in equal numbers and occurs in all ethnic groups and geographic regions in the world. Most estimates place the incidence between 1 in 10,000-30,000 individuals in the general population and about 350,000-400,000 individuals worldwide.
A diagnosis of PWS is based upon a detailed patient history, thorough clinical evaluation and identification of characteristic symptoms. Consensus diagnostic criteria for PWS have been established and are effective for identifying potential cases of PWS but genetic testing is required to confirm the diagnosis and to identify the specific genetic subtype (15q11-q13 deletion, maternal disomy 15, imprinting defect). Hence, all infants and newborns with unexplained hypotonia and poor suck should be tested for PWS. To confirm a diagnosis of PWS, certain specialized tests are required including DNA methylation tests and fluorescent in situ hybridization (FISH). More recently, high resolution chromosomal microarray studies with several hundred thousand DNA probes (e.g., 2.8 million probes) from throughout the genome representing all chromosomes can be utilized to identify small deletions or duplications of the chromosomes that cannot be seen with routine chromosome studies. High resolution chromosome microarrays are most useful in identifying the typical chromosome 15q11-q13 deletions in which there are two types (larger type I and smaller type II), other rearrangements of this chromosome region, imprinting defects and specific maternal disomy 15 subclasses seen in PWS. Genetic laboratory testing algorithms and advances in genetic technology have allowed more precise testing results and PWS molecular genetic class identified which is important as the severity of clinical findings, disease surveillance and recurrence risks can depend on the specific genetic abnormality.
Clinical Testing and Workup
Approximately 99% of people with PWS can be diagnosed by DNA methylation study. This test allows for the examination of gene activity status in the PWS/AS critical region of chromosome 15. If the methylation pattern is consistent with maternal inheritance, then this indicates that the paternal chromosome 15 is not present or not active. This finding is diagnostic of PWS, but methylation tests alone cannot distinguish among the different underlying causes of PWS (i.e., deletions, imprinting defects or maternal disomy 15).
If DNA methylation tests indicate PWS, then additional tests are necessary to determine the underlying cause of the disorder. This is important for determining whether there is an increased risk for the parents or other family members to have an affected child. High resolution microarrays have replaced the FISH test as microarrays can detect the size of the 15q11-q13 deletion, the most common genetic cause of PWS. High resolution microarrays can also detect maternal disomy 15 if present in the majority of those with PWS having no recognized deletion but both chromosome 15s come from the mother. There are two typical chromosomal 15q11-q13 deletion subtypes (larger type I and smaller type II) and three subclasses of maternal disomy 15 (heterodisomy, segmental isodisomy, total isodisomy) in PWS. Clinical and behavioral differences are reported in those with the PWS deletion subtypes or those with maternal disomy 15 subclasses. Those with the larger 15q11-q13 Type I deletion have more learning and behavioral problems and those with maternal disomy 15 are more prone to autistic findings and psychosis in young adulthood. If no deletion is present on chromosome 15, then additional testing is performed to distinguish between maternal disomy 15 or a defect of the imprinting center.
Prenatal diagnosis is possible in families with a previous history of PWS. Prior identification of a disease-causing abnormality can facilitate prenatal testing, but it is available by methylation analysis or high-resolution microarrays following amniocentesis regardless of cause.
Treatment
The treatment of PWS is directed toward the specific symptoms that are apparent in each individual. Early intervention and strict maintenance to treatment can greatly improve the overall health and quality of life for affected individuals and their families. Treatment may require the coordinated efforts of a team of specialists. Clinical geneticists, pediatricians, orthopedists, endocrinologists, speech therapists, psychologists, dieticians, nutritionists and other healthcare professionals may need to systematically and comprehensively plan an effective program for the childโs treatment. Genetic counseling is recommended for affected individuals and their families to further discuss the condition and to provide information and recurrence risks once genetic testing is completed for identification of specific PWS molecular classes. Parents are strongly recommended to learn appropriate parenting techniques for the behavioral and eating issues associated with PWS; such education correlates with better prognosis.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease severity; the presence or absence of certain symptoms; an individualโs age and general health; and/or other elements. Decisions concerning the use of drug regimens and/or other treatments should be made by physicians and other members of the health care team following pharmacogenetics or a personalized medicine approach to test for and identify DNA patterns of genes involved with coding proteins (e.g., liver enzymes) that breakdown or metabolism drugs or medications prescribed to treat a patient with PWS. Careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.
In infants, special nipples or gavage feeding may be used to ensure adequate nutrition. Gavage feeding is a procedure in which a small, thin tube is passed through the nose and mouth to the stomach to directly feed a newborn who has feeding difficulties.
In males, the treatment of hypogonadism with either testosterone or human chorionic gonadotropin may be beneficial during infancy, potentially increasing the size of the genitalia or prompting testicular descent into the scrotum when cryptorchidism is present. Although cryptorchidism may occasionally resolve spontaneously or with hormone therapy, most males require surgical treatment.
Individuals with PWS also benefit from growth hormone (GH) therapy, which can help to increase height, improve lean body mass, mobility and respiratory function, decrease body fat and ultimately improve the quality of life. Some studies have shown that GH therapy may improve development and behavior. In 2000, the U.S. Food and Drug Administration (FDA) approved the use of human growth hormone for the treatment of children with genetically confirmed PWS and evidence of growth failure. Studies have shown that the earlier GH therapy is started the more beneficial it is, and that therapy can begin as early as two to three months of age. GH therapy has been shown to improve facial appearance and overall body build (body habitus). Development of standardized growth charts for PWS with and without growth hormone treatment have been generated and can be used to monitor the growth parameters at specific ages in PWS. It is recommended that affected individuals undergo a sleep study to detect and treat obstructive sleep apnea before initiating GH therapy because some reports suggest a link between premature death and GH therapy in certain individuals with PWS (e.g., those with profound hypotonia or obesity and pre-existing respiratory or cardiac problems). However, other researchers have expressed doubt as to whether GH therapy had a direct role in these cases but decisions regarding GH therapy in individuals with PWS are best made after consultation with a pediatric endocrinologist after a sleep study and assessments for adrenal gland insufficiency.
Children with PWS require early intervention to assess and treat issues with motor skills, intellectual disability and speech and language development. Early intervention may include physical and occupational therapy, special education and speech therapy. An individualized education plan should be created at the start of school. Behavioral therapy and, in some patients, psychoactive medications such as specific serotonin reuptake inhibitors may be beneficial to manage difficult behavior or psychosis.
Children should receive an ophthalmological exam to evaluate eye abnormalities potentially associated with PWS such as strabismus and to assess visual acuity. Children should also be assessed for hip dysplasia and scoliosis which can occur in patients with PWS. Evaluation and treatment of sleep disturbance is recommended as well. Some researchers recommend that all individuals with PWS be screened for hypothyroidism (which occurs with increased incidence in PWS) and central adrenal insufficiency.
During childhood, a program consisting of a low-calorie diet, regular exercise and strict supervision of food intake and access should be formulated. Strict supervision of food intake should be based upon height, weight and body mass index (BMI). Such a program should begin before signs of obesity to help to prevent its development. Limiting access to food may require locking cabinets and refrigerators. Some individuals may require vitamin supplementation, especially calcium and vitamin D.
Sex hormones can be replaced at puberty as they can stimulate the development of secondary sexual characteristics and improve self-image and bone density. In males, the use of such therapy has been controversial because testosterone replacement by monthly injection may contribute to behavioral issues in males; use of a testosterone patch or gel will avert this problem. Sex hormone replacement therapy may increase the risk of stroke in females, as in the general population, and hygiene issues should also be considered. Sex education and consideration of contraception are important. Decreased flow of saliva may be improved with special toothpastes, gels, mouthwash and gum.
Clinical trials are underway to examine specific drugs or medications that may treat extreme hunger (hyperphagia), obesity, reduce medical problems associated with PWS and improve quality and length of life in affected individuals.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/for-patients-and-families/information-resources/news-patient-recruitment/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Butler MG, Lee PDK, Whitman B. Management of Prader-Willi Syndrome, 4th Edition, Springer, New York, 2022.
Hรถybye C. Prader-Willi Syndrome. Congenital Disorders: Laboratory and Clinical Research. Nova Science Publishers, New York, 2013.
Cassidy SB. Prader-Willi Syndrome. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:237-238.
JOURNAL ARTICLES
Butler MG, Hossain WA, Cowen N, Bhatnagar A. chromosomal microarray study in Prader-Willi syndrome. Int J Mol Sci. 2023 Jan 7;24(2):1220. doi: 10.3390/ijms24021220. PMID: 36674736; PMCID: PMC9863005
Mahmoud R, Kimonis V, Butler MG. Clinical trials in Prader-Willi syndrome: a review. Int J Mol Sci. 2023 Jan 21;24(3):2150. doi: 10.3390/ijms24032150. PMID: 36768472; PMCID: PMC9916985.
Miller JL, Gevers E, Bridges N, Yanovski JA, Salehi P, Obrynba KS, Felner EI, Bird LM, Shoemaker AH, Angulo M, Butler MG, Stevenson D, Abuzzahab J, Barrett T, Lah M, Littlejohn E, Mathew V, Cowen NM, Bhatnagar A; DESTINY PWS Investigators. Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1676-1685. doi: 10.1210/clinem/dgad014. PMID: 36639249; PMCID: PMC10271219.
Roof E, Deal CL, McCandless SE, Cowan RL, Miller JL, Hamilton JK, Roeder ER, McCormack SE, Roshan Lal TR, Abdul-Latif HD, Haqq AM, Obrynba KS, Torchen LC, Vidmar AP, Viskochil DH, Chanoine JP, Lam CKL, Pierce MJ, Williams LL, Bird LM, Butler MG, Jensen DE, Myers SE, Oatman OJ, Baskaran C, Chalmers LJ, Fu C, Alos N, McLean SD, Shah A, Whitman BY, Blumenstein BA, Leonard SF, Ernest JP, Cormier JW, Cotter SP, Ryman DC. Intranasal carbetocin reduces hyperphagia, anxiousness, and distress in Prader-Willi syndrome: CARE-PWS Phase 3 Trial. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1696-1708. doi: 10.1210/clinem/dgad015. PMID: 36633570; PMCID: PMC10271225.
Angulo MA, Butler MG, Hossain WA, Castro-Magana M, Corletto J. Central adrenal insufficiency screening with morning plasma cortisol and ACTH levels in Prader-Willi syndrome. J Pediatr Endocrinol Metab. 2022 Apr 20;35(6):733-740. doi: 10.1515/jpem-2022-0074. PMID: 35437976.
Forster J, Duis J, Butler MG. Pharmacogenetic testing of cytochrome P450 drug metabolizing enzymes in a case series of patients with Prader-Willi syndrome. Genes (Basel). 2021 Jan 24;12(2):152. doi: 10.3390/genes12020152. PMID: 33498922; PMCID: PMC7912498.
Godler DE, Butler MG. Special issue: genetics of Prader-Willi syndrome. Genes (Basel). 2021;12(9):1429. Published 2021 Sep 16. doi:10.3390/genes12091429
Pellikaan K, Ben Brahim Y, Rosenberg AGW, Davidse K, Poitou C, Coupaye M, Goldstone AP, Hรธybye C, Markovic TP, Grugni G, Crinรฒ A, Caixร s A, Eldar-Geva T, Hirsch HJ, Gross-Tsur V, Butler MG, Miller JL, van der Kuy PM, van den Berg SAA, Visser JA, van der Lely AJ, de Graaff LCG. Hypogonadism in women with Prader-Willi syndrome-clinical recommendations based on a Dutch cohort study, review of the literature and an international expert panel discussion. J Clin Med. 2021 Dec 10;10(24):5781. Doi: 10.3390/jcm10245781. PMID: 34945077; PMCID: PMC8707541.
Pellikaan K, Ben Brahim Y, Rosenberg AGW, Davidse K, Poitou C, Coupaye M, Goldstone AP, Hรธybye C, Markovic TP, Grugni G, Crinรฒ A, Caixร s A, Eldar-Geva T, Hirsch HJ, Gross-Tsur V, Butler MG, Miller JL, van den Berg SAA, van der Lely AJ, de Graaff LCG. Hypogonadism in adult males with Prader-Willi syndrome-clinical recommendations based on a Dutch cohort study, review of the literature and an international expert panel discussion. J Clin Med. 2021 Sep 24;10(19):4361. doi: 10.3390/jcm10194361. PMID: 34640379; PMCID: PMC8509256.
Strom SP, Hossain WA, Grigorian M, Li M, Fierro J, Scaringe W, Yen HY, Teguh M, Liu J, Gao H, Butler MG. A streamlined approach to Prader-Willi and Angelman syndrome molecular diagnostics. Front Genet. 2021 May 11;12:608889. doi: 10.3389/fgene.2021.608889. PMID: 34046054; PMCID: PMC8148043.
Veatch OJ, Malow BA, Lee HS, Knight A, Barrish JO, Neul JL, Lane JB, Skinner SA, Kaufmann WE, Miller JL, Driscoll DJ, Bird LM, Butler MG, Dykens EM, Gold JA, Kimonis V, Bacino CA, Tan WH, Kothare SV, Peters SU, Percy AK, Glaze DG. Evaluating sleep disturbances in children with rare genetic neurodevelopmental syndromes. Pediatr Neurol. 2021 Oct;123:30-37. doi: 10.1016/j.pediatrneurol.2021.07.009. Epub 2021 Jul 24. PMID: 34388423; PMCID: PMC8429141.
Butler MG, Duis J. Chromosome 15 imprinting disorders: genetic laboratory methodology and approaches. Front Pediatr. 2020 May 12;8:154. doi: 10.3389/fped.2020.00154. PMID: 32478012; PMCID: PMC7235373.
Butler MG. Imprinting disorders in humans: a review. Curr Opin Pediatr. 2020 Dec;32(6):719-729. doi: 10.1097/MOP.0000000000000965. PMID: 33148967; PMCID: PMC8791075.
Forster J, Duis J, Butler MG. Pharmacodynamic gene testing in Prader-Willi syndrome. Front Genet. 2020 Nov 20;11:579609. doi: 10.3389/fgene.2020.579609. PMID: 33329716; PMCID: PMC7715001.
Butler MG, Miller JL, Forster JL. Prader-Willi syndrome โ clinical genetics, diagnosis and treatment approaches: an update. Curr Pediatr Rev. 2019;15(4):207-244. doi: 10.2174/1573396315666190716120925. PMID: 31333129; PMCID: PMC7040524.
Butler MG, Hartin SN, Hossain WA, Manzardo AM, Kimonis V, Dykens E, Gold JA, Kim SJ, Weisensel N, Tamura R, Miller JL, Driscoll DJ. Molecular genetic classification in Prader-Willi syndrome: a multisite cohort study. J Med Genet. 2019 Mar;56(3):149-153. doi: 10.1136/jmedgenet-2018-105301. Epub 2018 May 5. PMID: 29730598; PMCID: PMC7387113.
Duis J, van Wattum PJ, Scheimann A, Salehi P, Brokamp E, Fairbrother L, Childers A, Shelton AR, Bingham NC, Shoemaker AH, Miller JL. A multidisciplinary approach to the clinical management of Prader-Willi syndrome. Mol Genet Genomic Med. 2019 Mar;7(3):e514. doi: 10.1002/mgg3.514. Epub 2019 Jan 29. PMID: 30697974; PMCID: PMC6418440.
Hartin SN, Hossain WA, Francis D, Godler DE, Barkataki S, Butler MG. Analysis of the Prader-Willi syndrome imprinting center using droplet digital PCR and next-generation whole-exome sequencing. Mol Genet Genomic Med. 2019 Apr;7(4):e00575. doi: 10.1002/mgg3.575. Epub 2019 Feb 21. PMID: 30793526; PMCID: PMC6465664.
Kimonis VE, Tamura R, Gold JA, Patel N, Surampalli A, Manazir J, Miller JL, Roof E, Dykens E, Butler MG, Driscoll DJ. Early diagnosis in Prader-Willi syndrome reduces obesity and associated co-morbidities. Genes (Basel). 2019 Nov 6;10(11):898. doi: 10.3390/genes10110898. PMID: 31698873; PMCID: PMC6896038.
Butler MG, Kimonis V, Dykens E, Gold JA, Miller J, Tamura R, Driscoll DJ. Prader-Willi syndrome and early-onset morbid obesity NIH rare disease consortium: A review of natural history study. Am J Med Genet A. 2018;176(2):368-375.
Hartin SN, Hossain WA, Weisensel N, Butler MG. Three siblings with Prader-Willi syndrome caused by imprinting center microdeletions and review. Am J Med Genet A. 2018 pr;176(4):886-895. doi: 10.1002/ajmg.a.38627. Epub 2018 Feb 13. PMID: 29437285; PMCID: PMC6688622.
Manzardo AM, Loker J, Heinemann J, Loker C, Butler MG. Survival trends from the Prader-Willi Syndrome Association (USA) 40-year mortality survey. Genet Med. 2018;20(1):24-30.
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INTERNET
Driscoll DJ, Miller JL, Cassidy SB. Prader-Willi Syndrome. 1998 Oct 6 [Updated 2023 Mar 9]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviewsยฎ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1330/ Accessed July 12, 2023.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:176270; Last Update: 11/21/2022. Available at: https://omim.org/entry/176270 Accessed July 12, 2023.
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NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
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Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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