Prader-Willi Syndrome by Ray Sahelian, M.D.
January 25 2016

Prader-Willi syndrome is characterized by hypothalamic dysfunction resulting in obesity, hypotonia, hypogonadism, and behavioral abnormalities. Clinical features of Prader-Willi syndrome resemble those of growth hormone deficiency (decreased total lean body mass, IGF-I levels, and poor linear growth). Marked reductions in muscle mass are associated with diminished strength, physical function, and energy expenditure. Lifelong morbidities of Prader-Willi syndrome include osteoporosis, type 2 diabetes mellitus, respiratory disorders, and cardiorespiratory failure related to obesity and hypotonia.

Clin Anat. 2016. Prader-willi syndrome: A spectrum of anatomical and clinical features. Prader-Willi Syndrome (PWS) is estimated to affect 400,000 people worldwide. First described clinically in 1956, PWS is now known to be a result of a genetic mutation, involving Chromosome 15. The phenotypical appearance of individuals with the syndrome follows a similar developmental course. During infancy, universal hypotonia accompanied by feeding problems, hypogonadism and dolichocephaly are evident. Characteristic facial features such as narrow bifrontal diameter, almond-shaped eyes and small mouth (with downturned corners and thin upper lip) may also be evident at this stage. In early childhood, the craniofacial features become more obvious and a global developmental delay is observed. Simultaneously, individuals develop hyperphagia that leads to excessive or rapid weight gain, which, if untreated, exists throughout their lifespan and may predispose them to numerous, serious health issues. The standard tool for differential diagnosis of PWS is genetic screening, however, clinicians also need to be aware of the characteristic features of this disorder, including differences between the genetic sub-types.

HGH and Prader-Willi Symdrome
HGH helps hundreds of children with a rare disorder that causes them to gorge on food, but for some, starting HGH treatment can worsen a dangerous nighttime breathing problem. Sleep apnea disrupts breathing during sleep and is common among morbidly obese children, including those with Prader-Willi syndrome, a disease that compels them to eat nonstop. Researchers say that uncovering how to treat obesity and related problems in children genetically wired to be overweight could help them better battle childhood obesity in general. HGH has shown to be one of the most effective ways to treat children and adults with Prader-Willi. But researchers found that starting HGH treatment can worsen or trigger sleep apnea in obese children exposed to colds, potentially leading to death. Source: The Journal of Clinical Endocrinology and Metabolism, Jan 2006.

Children with Prader-Willi syndrome who start taking recombinant human growth hormone (hGH) early in life have better body composition and functional strength compared to untreated children. Aaron Carrel, MD, of the University of Wisconsin Children's Hospital, treated 21 children, ages 6 to 9, with hGH 1 mg/m2/day for 6 years (starting as early as 4 months of age). The treatment-na´ve group consisted of 27 age- and gender-matched patients who had never received hGH.A Children treated with hGH had lower mean body fat than hGH-na´ve children. They also were taller and had better cholesterol profiles. J Clin Endocrinol Metab 2010 has the study by Aaron Carrel, MD.

Compr Physiol. 2012. Genetic diseases: congenital central hypoventilation, Rett, and Prader-Willi syndromes. The present review summarizes current knowledge on three rare genetic disorders of respiratory control, congenital central hypoventilation syndrome (CCHS), Rett syndrome (RTT), and Prader-Willi syndrome (PWS). CCHS is characterized by lack of ventilatory chemosensitivity caused by PHOX2B gene abnormalities consisting mainly of alanine expansions. RTT is associated with episodes of tachypneic and irregular breathing intermixed with breathholds and apneas and is caused by mutations in the X-linked MECP2 gene encoding methyl-CpG-binding protein. PWS manifests as sleep-disordered breathing with apneas and episodes of hypoventilation and is caused by the loss of a group of paternally inherited genes on chromosome 15. CCHS is the most specific disorder of respiratory control, whereas the breathing disorders in RTT and PWS are components of a more general developmental disorder. The main clinical features of these three disorders are reviewed with special emphasis on the associated brain abnormalities. In all three syndromes, disease-causing genetic defects have been identified, allowing the development of genetically engineered mouse models. New directions for future therapies based on these models or, in some cases, on clinical experience are delineated. Studies of CCHS, RTT, and PWS extend our knowledge of the molecular and cellular aspects of respiratory rhythm generation and suggest possible pharmacological approaches to respiratory control disorders. This knowledge is relevant for the clinical management of many respiratory disorders that are far more prevalent than the rare diseases discussed here.

Emails
Q. My son William was born in July 2001 with Prader-Willi Syndrome. At the age of 3 months William was still sleeping 20 plus hours a day had no normal wake / sleep pattern when I found information regarding Prader-Willi Syndrome and the benefits of coenzyme q10. I immediately ordered coenzyme q10 and began giving William 90 mg daily he almost immediately responded with a normal wake / sleep pattern. Have you done any research with coenzyme q10 and Prader-Willi Syndrome? I'm very interested in any research information you may have.
   A. We have not evaluated this condition in relation to coenzyme q10, however we will mention it on our website and maybe others with this condition may try it, with their doctor's supervision, and give us feedback.