Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings

Abstract

IntroductionPrader-Willi syndrome (PWS) is a multisystemic complex genetic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. There are three main genetic subtypes in PWS: paternal 15q11-q13 deletion (65–75 % of cases), maternal uniparental disomy 15 (20–30 % of cases), and imprinting defect (1–3 %). DNA methylation analysis is the only technique that will diagnose PWS in all three molecular genetic classes and differentiate PWS from Angelman syndrome. Clinical manifestations change with age with hypotonia and a poor suck resulting in failure to thrive during infancy. As the individual ages, other features such as short stature, food seeking with excessive weight gain, developmental delay, cognitive disability and behavioral problems become evident. The phenotype is likely due to hypothalamic dysfunction, which is responsible for hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency. Obesity and its complications are the major causes of morbidity and mortality in PWS.MethodsAn extensive review of the literature was performed and interpreted within the context of clinical practice and frequently asked questions from referring physicians and families to include the current status of the cause and diagnosis of the clinical, genetics and endocrine findings in PWS.ConclusionsUpdated information regarding the early diagnosis and management of individuals with Prader-Willi syndrome is important for all physicians and will be helpful in anticipating and managing or modifying complications associated with this rare obesity-related disorder.

Low dose growth hormone treatment in infants and toddlers with Prader-Willi syndrome is comparable to higher dosage regimens

“…IGF-I values above the reference range increased in the cohort from 19% to 37% and 36% after 1, 2 and 3 years of GHT respectively. This percentage is still of some concern as elevated IGF-I levels may contribute to lymphoid hyperplasia and associated OSA in young children after commencing GHT [32]. However, the percentage of children with elevated IGF-I levels was considerably less when compared to other studies using a higher dose of 7 mg/m 2 /week, in which the majority of children had an IGF-I level over 2 SDS after 2 or more years of treatment [29,33] despite a similar linear growth response.…”

Pain insensitivity in a child with a de novo interstitial deletion of the long arm of the chromosome 4: Case report

“…Absence of reaction to noxious or painful stimuli Autosomal recessive disease caused by a mutation in tRKA gene located on chromosome 1 (1q21-q22) encoding the highaffinity tyrosine kinase receptor NTRK1 for nerve growth factor (NGF) 7 , whereas a high pain threshold is a very common symptom in Prader-Willi syndrome, its sister syndrome 8 . Other authors observed a high pain tolerance in 86% of children with chromosome 15q duplication syndrome 9 , and this clinical features is more evident in case of isodicentric mutations rather than in the interstitial forms in which the load of duplicate genes is less.…”

Etiología del autismo: el continuo idiopático-sindrómico como tentativa explicativa

“…Como dificultades presentes a lo largo del ciclo vital de los sujetos con SPW destacan: hipotonía, baja estatura, hiperfagia, discapacidad cognitiva, así como diversos problemas conductuales. El fenotipo, posiblemente, esté causado por disfunción hipotalámica, siendo responsable de la hiperfagia, hipersomnia y de múltiples anormalidades endocrinas, incluyendo déficits en el crecimiento de la hormona estimuladora del tiroides, hipogonadismo e insuficiencia adrenal central 14 .…”