Prader Willi syndrome

Brilliant, M. H. (1992). The mouse pink-eyed dilution locus—a model for aspects of Prader-Willi-syndrome, Angelman syndrome, and a form of hypomelanosis of Ito. Mamm. Genome 3 187-191. 

Yang T, Adamson TE, Resnick JL et al 1998 A mouse model for Prader-Willi syndrome imprinting-centre mutations. Nat Genet 19 25—31... 

Ohta T, Gray TA, Rogan PK et al. Imprinting-mutation mechanisms in Prader-Willi syndrome. Am ) Hum Genet 1999 64[2] 397-413. 

The phenomenon of imprinting refers to the fact that a small number of human genes are transcriptionally active only when transmitted by one of the two sexes. A good example is provided by Prader-Willi syndrome, a disorder characterized by moderate mental retardation, hypogonadism, small hands and feet, and obesity. Most cases of Prader-Willi syndrome are caused by a deletion of 4 million bases (4 megabases or Mb) on the long arm of chromosome 15. However, the deletion produces this syndrome only if it is transmitted by the fether. If the same deletion is... 

The Inheritance of a deletion on chromosome IS from a male produces Prader-Willi syndrome, whereas inheritance of the same deletion from a female produces Angelman syndrome. 

The imprinted region of chromosome 15 contains about 8 genes, one of which is responsible, when broken, for Angelman syndrome—a gene called UBE3A. Beside this gene are the two top candidates for the Prader-Willi syndrome when broken one called the SNRPN gene and the other called IPW. 

Prader-Willi syndrome arises when deleted chromosome 15 is paternally inherited. 

The precise biochemical defect for Prader-Willi syndrome is unknown, but this region of chromosome 15 encompasses an imprinting control center and at least 6 maternally imprinted genes. 

Patients with Prader-Willi syndrome exhibit failure to thrive and short stature initially, which converts to a tendency toward excessive eating, obesity, mild-to-moderate mental retardation, hypogonadism, and characteristic facial dysmorphology. 

Angelman and Prader-Willi syndromes are related disorders affecting genes on chromosome 15 by which of the following epigenetic mechanisms ... 

D. B. Allen, Sustained benefit after 2 years of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome. J Pediatr, 2000.137(1) 42-9. 

Growth failure due to an inadequate secretion of endogenous growth hormone, Prader-Willi syndrome (PWS), adults with growth hormone deficiency (GHD) of either childhood- or adult-onset etiology... 

Established indications for somatropin (growth hormone) include growth hormone deficiency in children, Turner s syndrome, Noonan s syndrome, and renal insufficiency in children. Other well-studied indications include idiopathic short stature, adult growth hormone deficiency, osteoporosis, and catabolic states associated with acute and chronic illness and injury. Body composition, respiratory muscle function, physical strength, and height improved in a 12-month trial of somatropin in 54 children with Prader-Willi syndrome (1). 

Thyroid function tests are often altered by somatropin because of increased conversion of T4 to T3, but this is clinically insignificant at low doses (SEDA-21, 453). One child with Prader-Willi syndrome had a fall in serum thyroxine concentration during somatropin therapy and needed thyroxine replacement (33). Hypothyroidism developed in 11 of 46 growth hormone-deficient children treated with somatropin (34). Prior abnormalities in hypothalamic-pituitary function and alterations in thyroid hormone metabolism, probably both, contributed to the high incidence of hypothyroidism, which was similar to that in previous studies. 

A 13-year-old boy with Prader-Willi syndrome and steatohepatitis was given growth hormone 0.23 mg/kg/ week (63). His HbAic concentration before treatment was 5.6%. Four weeks later he developed diabetic ketoacidosis. He was given insulin and the growth hormone was withdrawn. Insulin was then gradually withdrawn and blood glucose concentrations remained normal for the next 6 months. 

The KIGS/KIMS (Pharmacia International Growth Database) has reported 233 patients with Prader-Willi syndrome, of whom three developed carbohydrate intolerance. 

Nine deaths have been reported in children with Prader-Willi syndrome receiving growth hormone. Pfizer issued a safety warning for growth hormone and Prader-Willi syndrome after reviewing seven deaths in male subjects (89). There was an association with severe obesity and severe respiratory impairment. 

Reports of sudden unexplained death in Prader-Willi syndrome in association with growth hormone have generally been in boys. Two deaths in girls have now been reported (91). 

A 4-year-old girl with Prader-Willi syndrome had an adenoidectomy for severe snoring, and growth hormone was started at a dose of 0.24 mg/kg/week. Suddenly, 7 weeks later, she died at home of cardiorespiratory failure. 

A 9-year-old girl with trisomy 21 and Prader-Willi syndrome started growth hormone treatment 0.14 mg/ kg/week. She had previously received growth hormone 0.28 mg/kg/week for 12 months at the age of 7 years, but therapy had been stopped at the family s request. Six months later she developed a respiratory infection and died. 

In a review of sudden death in patients with Prader-Willi syndrome, those who received growth hormone were compared with those who had not (92). Death between the ages of 3 and 15 years seemed to be more common in those who had received growth hormone than in those who had not. The dose of growth hormone, obesity, and respiratory problems may have been... 

Lindgren AC. Side effects of growth hormone treatment in Prader-Willi syndrome. Endocrinologist 2000 10(Suppl l) S63-4. 

Yigit S, Estrada E, Bucci K, Hyams J, Rosengren S. Diabetic ketoacidosis secondary to growth hormone treatment in a boy with Prader-Willi syndrome and steatohe-patitis. J Ped Endocrinol Metab 2004 17 361 —4. 

Allen DB, Carrel AL, Growth hormone therapy for Prader-Willi syndrome a critical appraisal. J Ped Endocrinol Metab 2004 17 1297-306. 

---