General information about Prader-Willi syndrome
A highly complex genetic neurodevelopmental disorder that affects many organs and with life-threatening issues.
Described in 1956 by three Swiss doctors – Andrea Prader, Alexis Labhart and Heinrich Willi – Prader-Willi syndrome affects around one in every 15,000 to 30,000 births (Orphanet).
It is a complex neurodevelopmental disorder of genetic origin, resulting from a defect in the expression of certain maternally imprinted genes in the 15q11-q13 region of chromosome 15, transmitted by the father (Nicholls, 1989; Nicholls, 2001).
Defects in the expression of these genes lead to abnormalities in the development and function of the hypothalamus (Goldstone, 2008; Tauber, 2021).
The hypothalamus is an essential structure of the central nervous system located at the base of the brain, mainly involved in the regulation of major functions such as hunger, thirst, sleep and body temperature. The hypothalamus is also involved in attachment, sexual behaviour and emotions, and controls many hormonal functions, acting on the pituitary gland, which secretes several hormones including growth hormone, certain sex hormones and thyroid hormones.
In addition to characteristic morphological features, Prader-Willi syndrome is characterised by a particular and complex neurodevelopmental trajectory throughout life, associated with nutritional, endocrine/metabolic and behavioural changes (Hoybye, 2022; Tauber, 2021, Cassidy, 2012; Miller, 2011).
The clinical picture therefore varies throughout life, but also from one individual to another, combining the following, to different degrees:
– Nutritional phases, described by Miller et al. (Miller, 2011): from anorexia with hypotonia and early orality difficulties at birth to excessive weight gain and then hyperphagia with lack of satiety and high risk of obesity in adult life,
– Swallowing problems (dysphagia) that persist at all ages, with an increased risk of serious and even fatal complications (Gross, 2016; Stevenson, 2007; Butler 2017),
– Various hormonal deficiencies: growth hormone (leading to short stature), hypogonadism, hypothyroidism and, more rarely, central adrenal insufficiency,
– Intellectual disability: mild to moderate cognitive deficit, delayed motor and language development, learning difficulties,
– Behavioural disorders, with deficits in social skills, emotional dysregulation, anxiety, compulsive symptoms and possible psychiatric disorders.
– In parallel, various co-morbidities occur throughout life such as: diabetes and other metabolic disorders, cardiovascular problems, gastrointestinal problems, central and obstructive apnoeas, major orthopaedic conditions (hip dysplasia, kyphosis and scoliosis), and ophthalmological pathologies (Hoybye, 2022; Tauber, 2021; Cassidy, 2012; Goldstone, 2008; Miller, 2011; Dykens, 2003).
This complex combination of somatic and behavioural/psychiatric disorders can lead to serious complications and treatment difficulties, significantly impacting patients with Prader-Willi syndrome and their families and carers (Kayadjanian, 2018; Meade, 2021). The treatment of Prader-Willi syndrome requires an integrative and collaborative multidisciplinary somatic and psychological approach throughout the life of the patient (Duis, 2018; Goldstone 2008; National Treatment Protocol, Prader Willi syndrome, 2021; Cassidy, 2012; Dykens, 2003; Goldstone, 2004; Miller, 2012).
There is currently no treatment for Prader-Willi Syndrome
Growth hormone is the only drug authorised for the indication of Prader-Willi Syndrome, with the aim of improving growth and body composition.
It is usually administered from the first year of life onwards.