[MIM 190 265]

(Trisomy 21, 'mongolism')

Prevalence estimated at 1/700 births. It increases with the mother's age: from 1/1500 at 20 years to 1/100 at 40 years of age).  Chromosomal anomaly (complete, partial or mosaic) characterized by the presence of one supernumerary chromosome 21 (free trisomy 21) or an anomaly of one of the  chromosomes 21 containing the genetic content of 2 chromosomes 21 (trisomy 21 translocation). 

Clinical presentation:

-        typical facies: midface hypoplasia, almond-shaped eyes; epicanthus; macroglossia with protruding tongue

-         single palmar crease

-        mental retardation of varying importance

-        high rate of premature birth with risk of pulmonary arterial hypertension (triggered by a trend towards alveolar simplification ?)

-        congenital heart disease (50 %): mainly atrio-ventricular canal; VSD, ASD

-        significant risk of peri- and post-natal pulmonary arterial hypertension: chromosome 21 carries 3 antiangiogenic genes, which leads to a more or less significant reduction in the development of the pulmonary vascularization. This results in the variable association of: 1) a smaller and less compliant LV than in the normal population (diastolic dysfunction: increased pulmonary venous pressures), 2) systolic and diastolic dysfunction of  the RV, 3) decreased pulmonary alveolization (secondary to the underdevelopment of the pulmonary vascular tree), 4) persistence of a two layers pulmonary capillary bed and  5)  decreased response to NO. In that context, the presence of a left-to-right shunt increases the pulmonary bloodflow and favors the development of early pulmonary arterial hypertension.

-        narrow pharynx; sometimes cleft palate

-        subglottic stenosis, sometimes tracheomalacia

-        obstructive sleep apnea

-        autonomic dysfunction: increased vagal tone, arterial hypotension and sinusal arrhythmia more frequent than in the non-affected normal population

-        increased risk of hypothermia

-        hypotonia and joint laxity

-        duodenal atresia

-          hypothyroidism

-        Hirschsprung's disease

-         increased risk for gallblader lithiasis

-         Brushfield sposts on the iris of the eyes

-        immune deficiency; high risk of megakaryoblastic leukemia with leukocytosis (first months of life) (GATA1 gene) or myeloid leukemia (JACK2 gene)

-        short stature, short neck with instability of the atloaxoid, atlo-occipital or other cervical vertebrae (30 %, but only 1 to 2 % are symptomatic); odontoid bone (odontoid process of the axis separated from his body, see this term, present in 6 %)

Anesthetic implications:

• regular echocardiography as abnormalities may only appear in childhood or adolescence (valvular insufficiency, LVH, rhythm disorders..)
• check total blood count and thyroid function
• echocardiography
• risk of instability of C1 on C2 and hypoplasia of the posterior arch of C1 : preoperative dynamic XRays of the cervical spin and advice from the  neurosurgeon are necessary only if neurological signs or symptoms (torticollis, behavioral change, walking problems) are present.  Careful positioning of the head and neck during intubation: significant cervical flexion and extension are to be avoided during laryngoscopy . Avoid any important lateral rotation of the head : it is better to tilt the operating table
• significant risk of bradycardia and hypotension during inhalation induction with sevoflurane (specially if combined with N2O), even in the absence of any heart disease; respiratory arrhythmia more frequent than in the non-affected normal population
• risk upper airway obstruction during  induction and awakening of anesthesia (hypotonia, obstructive sleep apnea)
• an endotracheal one size smaller than calculated for age / weight should be used
• if an arterial catheter is required, it is wise to check the patency of the radial and ulnar arteries by echography as the incidence of hypoplastic or abnormal radial artery is higher than in the general population.
• contrary to a common belief, trisomic 21 children require similar perioperative dosing of opioids as non trisomic 21 children

References : 

-        Lo RN, Leeung MP, Lau KC, Yeung CY.
Abnormal radial artery in Down’s syndrome.
Arch Dis Child 1986; 61: 885-90.

-        Mitchell V, Howard R, Facer E.
Down's syndrome and anaesthesia.
Paediatr Anaesth 1995; 5 :379-84. 

-        Roodman S, Bothwell M, Tobias JD.
Bradycardia with sevoflurane induction in patients with trisomy 21.
Pediatr Anesth 2003 ; 13 : 538-40

-   Borland LM, Colligan J, Brandom BW.
Frequency of anesthesia-related complications in children with Down syndrome under general anesthesia for non-cardiac procedures.
Pediatr Anesth 2004 ; 14 : 733-8.

-   Hata T, Todd MM.
Cervical spine considerations when anesthetizing patients with Down syndrome.
Anesthesiology 2005; 102: 680-5.

-        Kraemer FW, Stricker PA, Gurnaney HG, McClung H, Meador MR, Sussman E, Burgess BJ, Ciampa B, Mendelsohn J, Rehman MA, Watcha MF.
Bradycardia during induction of anesthesia with sevoflurane in children with Down syndrome.
Anesth Analg 2010; 111: 1259-63.

-        Bai W, Voepel-Lewis T, Malviya S.
Hemodynamic changes in children with Down syndrome during and following inhalation induction of anesthesia with sevoflurane.
J Clin Anesth 2010; 22:592-7.

-        Feldman-Lewanda A, Matisoff A, Revenis M, Harashsheh A, Futterman C et al.
Preoperative evaluation and comprehensive risk assessment for children with Down syndrome.
Pediatr Anesth 2016; 26: 356-62. 

-        Walia H, Ruda J, Tobias JD.
Sevoflurane and bradycardia in infants with trisomy 21 : a case report and review of the literature.
Int J Pediatr Otorhinolaryngol 2016 ; 80 :5-7

-        Bertolizio G, Saint-Martin C, Ingelmo P.
Cervical instability in patients with Trisomy 21 : the eternal gamble.
Pediatr Anesth 2018 ; 28: 830-3

-        Clauss SB, Gidding SS, Cochrane CI, Walega R, Zemel BS et al.
Prevalence of unsuspected abnormal echocardiograms in adolescents with Down syndrome.
Am J Med Genet A 2019 ; 179 : 2420-4

-        Graber TJ, Baskin PL, Soria C, Greenberg M, Gabriel RA, Brzenski A.
An assessment of perioperative respiratory adverse events and difficult intubation in pediatric patients with Trisomy 21.
Pediatr Anesth 2021; 31:410-8.

-        Vogel E, Staffa S, DiNardo J.
Dosing of opioid medications during and after pediatric cardiac surgery for children with Down syndrome.
J Cardiothorac Vasc Anesth 2022; 36:195-9

-        Sinton JW, Cooper DS, Wiley S.
Down syndrome and the autonomic nervous system, an educational review for the anesthesiologist.
Pediatr Anesth 2022; 32: 609-16.

-        Smith A, Bussmann N, Breatnach C, Levy PT, Molloy E, Miletin J et al.
Relationship between postnatal pulmonary arterial pressure and altered diastolic function in neonates with Down syndrome.
J Pediatr 2022; 245:172-8.

-        Adler AC, Nguyen H-Y, Nathanson BH, Chandrakantan A.
Incidence of hypotension during sevoflurane induction in children with Down syndrome; a prospective observational study.
Pediatr Anesth 2023;33:259–262.DOI: 10.1111/pan.14604 

Updated: March 2023