What are the symptoms? Severe hypotonia at birthFeeding difficulties at firstHypogonadism (undescended testicles in males, reduced or lacking menstruation in females)Mild to moderate intellectual disabilities (see entry Learning Disability)Obesity (in the absence of food restrictions this appears to be universal). The syndrome often includes: short staturedevelopmental delay in walking and speechobsessive behaviourstrabismus (squint)small hands and feetskin pickingscoliosis (spinal curvature)diabetes (see entry Diabetes Mellitus)challenging behaviourpsychiatric illnesses (usually starting in late adolescence and adulthood). The two main genetic subtypes (deletion and maternal disomy; see ‘What are the causes’) differ in many respects, including: average maternal age at birth, ‘fair for family’ pigmentation, cognitive strengths and weaknesses, and risk of depressive (greater in deletion subtype) and psychotic (greater in maternal disomy subtype) illnesses. The above characteristics, although typical of people with Prader-Willi syndrome in general, are not all universal and vary in severity. What are the causes? Prader-Willi syndrome is very rarely inherited. It occurs sporadically due to the loss of expression of maternally silenced genes on the chromosome 15 of paternal origin. Historically, approximately 70% of cases are due to a deletion, (missing segment), and in most other cases both copies of chromosome 15 are maternal in origin (maternal disomy) with no paternal copy. Genetic testing is undertaken using DNA and parental blood samples may be requested to confirm maternal disomy. How is it diagnosed? The condition is suspected if a baby has severe hypotonia, and if there is reduced foetal movement, breech presentation or other complications of pregnancy. Genetic testing is needed to confirm the diagnosis. Genetic testing is routine in known risk carriers. How is it treated? There is no cure for PWS. Dietary management is the cornerstone of managing the associated obesity. Typically, carers have to limit access to food and take over total control of food intake. Behaviour modification methods which rely on reinforcement and self-monitoring as part of weight control and exercise programmes are also required, though long-term maintenance of weight loss is difficult to achieve. Behaviour management is key in controlling the outbursts of rage and aggression, stubbornness and belligerence, which are common in affected individuals, beginning around age three to five and becoming more marked later in childhood and persisting into adulthood. Growth hormone supplements are also used to increase final stature and improve body composition and activity levels. Inheritance patterns and prenatal diagnosis Inheritance patterns People with PWS are usually infertile. If a male with deletion PWS fathers a child, it will have a 50% chance of inheriting PWS (no cases documented). If a female with deletion PWS gives birth, the child will have a 50% chance of being born with Angelman syndrome (one case documented). If a male with maternal disomy or imprinting centre defect fathers a child it will be normal if the imprint resets, otherwise it will be disomy PWS. If a female with maternal disomy or imprinting centre defect gives birth, the child will be normal (one case documented). Prenatal diagnosis Usually none at present. There may be reduced foetal movement. In the very rare known carrier families, amniocentesis may be recommended. Is there support? Prader-Willi Syndrome Association UK Helpline: 01332 365 676Email: email@example.comWebsite: pwsa.co.uk The Association is a Registered Charity in England and Wales No. 1155846. It provides information and support to anyone affected by Prader-Willi syndrome (PWS). The Association offers family days and weekends, regional events, peer to peer support and training. Group details last reviewed September 2019.