[MIM 176 270, 601 491]

(Prader-Willi-Labhardt syndrome)

Prevalence: 1/10,000 to 1/25.000. It is caused either by a 15q11 - q13 deletion of paternal origin (70 % of cases) or by a maternal disomy of chromosome 15 (20-25 %). Various clinical manifestations which seem to be the result of hypothalamic dysfunction.

Evolution in 4 phases:

-        neonatal period: hypotonia, feeding difficulties

-        childhood: overeating, hypogonadism, very rapid growth

-        childhood and adolescence: bulimia with truncal type obesity, often short stature, hypogonadism, behavioral  problems (temper tantrums, compulsive and obsessive disorders), mental retardation, epilepsy;in contrast to other forms of obesity, these patients generally have high levels of ghrelin

-        later: diabetes, scoliosis, chronic cor pulmonale, behavioral problems (theft, lies, aggressiveness).

Facial deformities:

-        dolichocephaly in childhood

-        narrow face, triangular mouth, almond-shaped eyes, small mouth, low forward implanted hair.

Hands and feet are small compared to the body size.

Respiratory abnormalities: central and obstructive apnea: in about 10 % of cases, the obstructive apneas seem to be worsened by the growth hormone therapy; restrictive lung disease linked to obesity, abnormal response to hypoxia and hypercarbia.

Micrognathia, dental caries, short and poorly mobile neck, thick saliva. Disorders of thermoregulation: hypo - and hyperthermia. Gastro-esophageal reflux, rumination and mericism.

Increased pain threshold. Some children receive growth hormone treatment to improve the ventilatory function, accelerate growth and prevent obesity, but cases of sudden death have been described. Increased cardiovascular risk: hypokinesia linked to the deficiency in growth hormone, early atheromatosis.

A risk of adrenocortical insufficiency of central origin is present: it increases with age.

It is characterized by normal cortisol levels at rest but a poor response in case of stress. This is why some teams propose to administer a dose of hydrocortisone at the induction of anesthesia.

Recommendations (Prof V Beauloye, Clin univ St Luc, Brussels):

1)        great caution is required in case of respiratory infection, even if apparently trivial. For the youngest ones, consider monitoring of ventilation for 24 hours. This is because obstructive sleep apnea, thick saliva, kyphoscoliosis or enlarged adenoids, associated with a narrow upper airway, obesity, and hypotonia of the respiratory muscles put the child in jeopardy during any respiratory infection.

2)        these children do not always present with fever: they may have a severe infection without temperature; a disturbance of the feeling of thirst leads to an increased risk of dehydration. In case of alteration of consciousness, it is necessary to exclude  dilution hyponatremia (unclear mechanism).

3)        increased sensitivity to drugs (especially psychotropic drugs), which justifies the use of low starting doses. Benzodiazepines are contraindicated !  There is a risk of respiratory depression with hypoxemia in case of oral clonidine administration at a dose > 4 µg/kg

4)        risk of inhalation due to their voracity (8% of deaths) and gastric rupture (2 % of all deaths) in case of  bulimic access. An inability to vomit  is often found in these patients and may complicate or delay the diagnosis of an acute abdominal situation. Vomiting, unusual in these children, should  raise the possibility of psychosis

5)        cortisol insufficiency, especially in case of stress, has been described in some patients: when in doubt, administer hydrocortisone (50 mg/m2/d < 12 years and 100 mg/m2/day > 12 years in 4 x) IM, IV or per os. However,  but the doses of dexamethasone usually given as prophylaxis for PONV are probably sufficient (0,75 mg dexamethasone = 20 mg hydrocortisone)

• anesthetic risk is more important in these patients who may present with respiratory complications (laryngospasm, risk of post-anesthetic apnea and hypoventilation ) and an increased thrombotic risk due to obesity. The PWS patients must be monitored for at least 24 hours after anesthesia.
• the pain threshold can be high, which can cause a delayed diagnosis of postoperative complications.
• because of the frequency of scratching, wound healing may be delayed or complicated by secondary infections.

Anesthetic implications:

problematic preoperative fasting (monitoring). Difficult venous access. Risk of airway obstruction. Gastroesophageal reflux. Restrictive lung disease. Abnormal response to hypoxia and hypercarbia. Caution with the alpha2-agonists (clonidine). Problems of thermoregulation: hypo - or hyperthermia. Preoperative echocardiography. Perioperative respiratory problems: laryngospasm, bronchospasm, atelectasis, apnea. Risk of adrenal insufficiency of central origin in childhood and adolescence: evaluate the adrenal function in the preoperative period or administer a dose of hydrocortisone at the induction of anesthesia.

References : 

• Dearlove OR, Dobson A, Super M. 
  Anaesthesia and Prader-Willi syndrome. 
  Paediatr Anaesth 1998; 8:267-71.
• Sloan TB, Kaye CI. 
  Rumination risk of aspiration of gastric contents in the Prader-Willi syndrome. 
  Anesth Analg 1991; 73: 492-5.
• Menendez AA. 
  Abnormal ventilatory responses in patients with Prader-Willi syndrome. 
  Eur J Pediatr 1999; 158: 941-2.
• Legrand R, Tobias JD. 
  Anesthesia and the Prader-Willi syndrome : preliminary experience with regional anesthesia. 
  Pediatr Anesth 2006; 16:712-22.
• de Lind van Wijngaarden RFA, Joosten KFM, van den Berg S, Otten  
  The relationship between central adrenal insufficiency and sleep-related breathing disorders in children with Prader-Willi syndrome. 
  J Clin Endocrinol Metab 2009; 94: 2387-93.
• Corrias A, Grugni G, Croino A, Di Candia et al. 
  Assessment of central adrenal insufficiency in children  and adolescents with Prader-Willi syndrome. 
  Clinical Endocrinology 2012; 76: 843-50.
• Barbara DW, Hannon JD, Hartman WR. 
  Intraoperative adrenal insufficiency in a patient with Prader-Willi syndrome. 
  J Clin Med Res 2012; 4: 346-8.
• Lam H, Landsman IS. 
  Are children with Prader-Willi syndrome at higher risk for anesthetic complications? 
  Pediatr Anesth 2014; 24: 457-9
• Haqq AM, Grambow SC, Muchlbauer M, Newgard CB et al.
  Ghrelin concentrations in Prader-Willi syndrome (PWS) infants and children: changes during development.
  Clin Endocrinol 2008; 69:911-20.
• Caudri D, Nixon GM, Nielsen A, Mai L, Hafekost CR et al.
  Sleep-disordered breathing in Australian children with Prader-Willi syndrome followig initiation of growth hormone therapy.
  J Paediatr Child Health 2022; 58 : 248-55

Updated: April 2022