Williams syndrome

(Williams-Beuren syndrome, 7q11.23 deletion , 7q11.23 monosomy )

Sporadic: prevalence 1/7,500. De novo deletion, of variable size, (26 to 28 genes) of chromosome 7q11.23. This mutation causes among others an elastin (ELN gene) deficiency in arterial walls: this arteriopathy due to lack of elastin causes hyperplasia of the smooth muscle in the arterial media.

Association to varying degrees of:

cardiovascular anomalies (80%):

- supravalvular-aortic stenosis (45-75%); either hourglass (75%) stenosis or stenosis of a long segment of the aorta with secondary hypertrophy of LV and often the RD

- distal pulmonary stenosis in 40%: this stenosis may be critical before the age of 1 year but seems to be improving with age due to the lower pressures in the pulmonary arterial system

- coronary lesions: ostial anomaly, winding coronary arteries, localized coronary dilations, secondary atheromatosis; severe coronary artery lesions may be present in the absence of significant valvular lesions

- stenosis at the level of the bifurcation of large arteries: risk of hypertension of renal origin, stenosis of the thoracic aorta (middle aortic syndrome), sometimes stenosis of the carotid or cerebral arteries

- structural heart abnormalities: VSD, aortic valve anomalies (adhesions at the sinotubular junction, bicuspid valve) especially in case of supravalvular stenosis (50%), mitral valve prolapse

- risk of sudden death, particularly in case of anesthesia, which appears to be linked to the presence of a long QT (13.6% of cases)

facial dysmorphism in "Elf facies": wide forehead, star shaped iris, upturned nose with anteverted nostrils, long philtrum, wide mouth, prominent lips, drooping cheeks,
idiopathic neonatal hypercalcemia with risk of nephrocalcinosis; hypercalcemia usually decreases in childhood
moderate mental retardation; hyperactivity disorder with very easy social contact and brisk responsiveness to noise; behavioural disorders probably associated with excessive anxiety or obsessions
endocrine problems: hypothyroidism, risk of diabetes mellitus, precocious puberty
sometimes Chiari malformation type I
damage to tooth enamel, dental malocclusion,
a ligamentous laxity, muscle weakness
gastroesophageal reflux disease
a high risk of colonic diverticulosis with attacks of diverticulitis starting in the adolescence.

Treatments: antihypertensive (calcium antagonists, β-blockers, minoxidil), treatment for the long Qt if present

Proposal for an anesthetic risk classification:

low	moderate	important
age > 20 years	arterial hypertension	age < 3 years previous cardiovascular problem
normal ECG	- moderate supravalvular aortic stenosis (< 40 mmHg gradient) or - moderate stenosis of a branch of the pulmonary artery	severe supravalvular aortic stenosis (> 40 mmHg gradient) and a signs of left ventricular hypertrophy at ECG
echocardiography: moderate supravalvular aortic or pulmonary stenosis	moderate obstruction to ejection for both ventricles	important obstruction to ejection for both ventricles
few extracardiac anomalies; no renal artery stenosis	stenosis of the renal artery	- diffuse involvement of the thoracic aorta - involvement of coronary arteries
	- QTc > 450 msec but < 500 msec	- QTc > 500 msec or - presence of arhythmias on preop ECG
	- upper airway anomalies - gastroesophageal reflux, pulmonary involvement	- LV or RV hypertrophy or - ischemia signs on ECG

Anesthetic implications:

preoperative: ECG and recent echocardiography.

Perianesthetic: ECG with 5 derivations; to be considered as at high risk for myocardial ischemia: avoid tachycardia, maintain sinus rhythm, preserve preload (avoid prolonged fasting and any hypovolemia) and afterload (avoid hypotension), maintain contractility and avoid any increase in lung resistance (hypoxemia, hypercarbia, ventilation pressures). Avoid high concentrations of sevoflurane; ideal: ketamine, etomidate, morphine, small doses of propofol.

Cardiac complications (11 % in a series), sudden death with very difficult resuscitation (cfr aortic stenosis and HVG). No risk of malignant hyperthermia.

One team has reported that, in case of mild or severe risk (see the table), the risk of systolic hypotension at induction and of the associated cardiac complications could be diminished by IV induction and rapid (even prophylactic) administration of a vasopressor.

References :

Kawahito S, Kitahata H, Kimura H, Tanaka K, Sakai Y, Hirose Y et al.
Anaesthetic management of a patient with Williams syndrome undergoing aortoplasty for supravalvular aortic stenosis.
Can J Anaesth 1998; 45:1203-6.
Andrzejowski J, Mundy J.
Anaesthesia for MRI angiography in a patient with Williams syndrome.
Anaesthesia 2000; 55:97-8.
Driessen JJ, van Oort AM, Booij LHDJ.
Severe myocardial ischaemia during mask induction of anaesthesia in an infant with unknown critical supravalvular aortic stenosis.
Anaesthesia 2003; 58: 568-70
Medley J, Russo P, Tobias JD.
Perioperative care of the patient with Williams syndrome.
Pediatr Anesth 2005; 15: 243-7.
Burch TM, McGowan FX, Kussman BD, Powell AJ, DiNardo JA. Congenital supravalvular aortic stenosis and sudden death associated with anesthesia : what is the mystery ?
Anesth Analg 2008; 107: 1848-54
Pober BR.
Williams-Beuren syndrome.
NEJM 2010; 362: 239-52.
Groenewald C, Latham GJ. An unexpected cause of cardiac arrest during laparoscopy in an infant with supravalvular aortic stenosis. Pediatr Anesth 2013; 23: 91-93
Collins RT II.
Cardiovascular disease in Williams syndrome.
Circulation 2013 ; 127 : 2125-34.
Olsen M, Fahy CJ, Costi DA, Kelly AJ, Burgoyne LL.
Anaesthesia-related haemodynamic complications in Williams syndrome patients: a review of one institution’s experience.
Anaesth Intensive Care 2014; 42: 619-24.
Collins RT.
Clinical significance of prolonged QTc interval in Williams syndrome.
Am J Cardiol 2011; 108: 471-3
Stagi S, Lapi E, Chiarelli F, de Martino M.
Incidence of diverticular disease and complicated diverticular disease in young patients with Williams syndrome.
Pediatr Surg Int 201; 26: 943-4.
Matisoff AJ, Olivieri L, Schwartz JM, Deutsch N.
Risk assessment and anesthetic management of patients with Williams syndrome : a comprehensive review.
Pediatr Anesth 2015; 25: 1207-15.
Deka S., Das J., Khanna S., Mehta Y., Mithra M.
A child of Williams-Beuren syndrome for inguinal hernia repair: perioperative management concerns.
Indian Anaesth Forum 2016; 17:62-64
Twite MD, Stenquist S, Ing RJ.
Williams syndrome.
Pediatr Anesth 2019�; 29�: 483-90.
Astuto M, Sapienza D, Di Benedetto V, Disma N.
Spinal anesthesia for inguinal hernia repair in an infant with Williams syndrome: case report.
Pediatr Anesth 2007; 17: 193-7
Schmidt AR, Collins RT II, Adusumelli Y, Ramamoorthy C, Weng Y, MacMillen KL, Navaratnam M.
Impact of modified anesthesia management for pediatric patients with Williams syndrome.
J Cardiothor Vasc Anesth 2021�; 35�:3667-74

Updated: January 2022