Connecting the PWS Dots

J Pediatr Gastroenterol Nutr. 2008 Jan;46(1):80-3.
Critical analysis of bariatric procedures in Prader-Willi syndrome.
Scheimann AO, Butler MG, Gourash L, Cuffari C, Klish W.
Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Johns Hopkins School of Medicine, 600 N Wolfe St, Brady 320, Baltimore, MD, USA.

Prader-Willi syndrome (PWS) is a complex genetic disorder localized to chromosome 15 and is considered the most common genetic cause of the development of life-threatening obesity. Although some morbidities associated with PWS, including respiratory disturbance/hypoventilation, diabetes, and stroke, are commonly seen in obesity, others such as osteoporosis, growth hormone deficiency, and hypogonadism, and also altered pain threshold and inability to vomit, pose unique issues. Various bariatric procedures have been used to cause gastric stasis, decrease gastric volume, and induce malabsorption, with poor results in PWS patients in comparison with normal obese individuals.

J Child Neurol. 2008 Jan;23(1):112-7.
Persistent Growth Failure in Prader-Willi Syndrome Associated With Short-Chain Acyl-CoA Dehydrogenase Gene Variant.
Giurgiutiu DV, Espinoza LM, Wood TC, Dupont BR, Holden KR.
Department of Neurosciences, Medical University of South Carolina, Charleston.

The authors report the rare association of Prader-Willi syndrome and short-chain acyl-CoA dehydrogenase gene variant. Prader-Willi syndrome, associated with paternal chromosome 15q11-q13 silencing, is characterized by neonatal/infantile hypotonia, growth failure, and neurodevelopmental delays in the first 1 to 2 years of life, typically followed by hyperphagia and obesity. Short-chain acyl-CoA dehydrogenase gene variant, with 625 G-to-A and 511 C-to-T changes, impairs C4-C6 fatty acid metabolism and variably causes neonatal/infantile hypotonia with developmental delays. The authors’ patient continues to exhibit the classic severe growth failure of early infancy Prader-Willi syndrome at 40 months. Extensive laboratory investigations indicate that the short-chain acyl-CoA dehydrogenase gene variant is likely preventing or delaying the normal expression of the Prader-Willi syndrome phenotype.

Int J Eat Disord. 2001 Jul;30(1):113-7.
Aggravation of food-related behavior in an adolescent with Prader-Willi syndrome treated with fluvoxamine and fluoxetine.
Kohn Y, Weizman A, Apter A.
Department of Psychiatry, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.

Prader-Willi Syndrome is a congenital multisystem disorder, characterized by a typical dysmorphism, mental retardation, hyperphagia due to insatiable appetite, and resultant morbid obesity. Psychiatric symptoms include obsessions and temper tantrums. Method: Pharmacotherapy is experimental with a few reports of successful fluoxetine treatment. Results: We report an aggravation in the food-related symptoms and a consequent weight gain in an adolescent with Prader-Willi syndrome, who was treated with fluvoxamine and fluoxetine.

Eur J Pediatr. 2001 Jan;160(1):69-70.
Premature adrenarche, increased growth velocity and accelerated bone age in male patients with Prader-Labhart-Willi syndrome.
Schmidt H, Schwarz HP.

Premature adrenarche/pubarche in male patients with Prader-Labhart-Willi syndrome may be associated with increased growth velocity and bone age acceleration.

Am J Med Genet. 1999 Jan 15;82(2):123-7.
Behavior and emotional disturbance in Prader-Willi syndrome.
Einfeld SL, Smith A, Durvasula S, Florio T, Tonge BJ.
School of Psychiatry, University of New South Wales, Kensington, Australia.

To determine if persons with the Prader-Willi syndrome (PWS) have increased psychopathology when compared with matched controls, and whether there is a specific behavior phenotype in PWS, the behavior of 46 persons with PWS was compared with that of control individuals derived from a community sample (N = 454) of persons with mental retardation (MR). Behaviors were studied using the Developmental Behaviour Checklist, an instrument of established validity in the evaluation of behavioral disturbance in individuals with MR. PWS subjects were found to be more behaviorally disturbed than controls overall, and especially in antisocial behavior. In addition, some individual behaviors were more common in PWS subjects than controls. When these behaviors are considered together with findings from other studies using acceptably rigorous methods, a consensus behavior phenotype for PWS can be formulated. This will provide a valid foundation for studies of the mechanism of genetic pathogenesis of behavior in PWS.

Minerva Pediatr. 1991 Sep;43(9):587-93.
Endocrine study in the Prader-Willi syndrome. Apropos of 5 cases. [Article in Italian]
Calisti L, Giannessi N, Cesaretti G, Saggese G.
Cattedra di Pediatria Preventiva e Sociale, Università di Pisa.

Five children (3 boys and 2 girls) ranging in age form 5-12 years and suffering from Prader-Willi syndrome have been evaluated. In each subject the Authors have examined auxological parameters and the following hormonal values: GH after two pharmacological stimuli tests, gonadotropins after LHRH, TSH and prolactin after TRH, cortisol rhythm, testosterone after hCG in males, thyroid hormones and steroids. The results have shown a height less than 3 [per]centile only in a subjects and ranging from 10 degrees-50 degrees in the others, a weight greater than 97 [per]centile for the height age in all, a low response in GH to both stimuli in two subjects, an increased response to LHRH in FSH in two subjects. All other endocrine evaluations were in the normal range with the exception of insulin that resulted augmented in spite of normal glycaemic values. In conclusion, our data would suggest the existence of an eventual alteration of the hypothalamus-pituitary structures.

Eur J Pediatr. 1982 Nov;139(3):201-3.
Primary gonadal failure and precocious adrenarche in a boy with Prader-Labhart-Willi syndrome.
Garty B, Shuper A, Mimouni M, Varsano I, Kauli R.

A 7-year-old boy with Prader-Labhart-Willi syndrome who had precocious adrenarche was found to have primary gonadal failure, as evidenced by appropriate laboratory investigations: elevated basal levels of plasma FSH and LH with exaggerated responses to LH-RH stimulation and unresponsiveness of plasma testosterone to repeated hCG stimulations. The elevated values of plasma DHEA which were found indicate an early activation of the adrenal gland. This patient demonstrates the variability of pubertal development in the Prader-Labhart-Willi syndrome, with the unusual association of primary gonadal failure and precocious adrenarche.

Dtsch Med Wochenschr. 1974 May 31;99(22):1196-8.
Hypogonadism due to luteotropin-releasing hormone (LHRH) deficiency in a child with Prader-Labhart-Willi syndrome (author’s transl). [Article in German]
Morgner KD, Geisthövel W, Niedergerke U, zur Mühlen A von.

No abstract available.