Genetic and Inherited Diseases

Trisomy 21 (Down Syndrome)

With an incidence of approximately1 in 700 live births , trisomy 21 is the most common chromosomal abnormality and the most common cause of intellectual disability associated with genetic disease. These children are characterized by their distinctive facial appearance ( Fig. 9.1 ) and a variety of possible disorders.

Surgical intervention is required for a number of disease entities that occur in children with trisomy 21 ( Table 9.1 ). Furthermore, a number of associated congenital anomalies may cause unique anesthetic-related challenges.

Preoperative evaluation should focus on delineation of associated comorbidities. Many children with trisomy 21 have only mild intellectual disability and will benefit from a full explanation of the perioperative process. An anxiolytic premedication such as oral midazolam should be ordered unless there are concerns about severe obstructive sleep apnea (OSA). Older children with trisomy 21 tend to have a large body mass index (BMI) which, along with developmental delay or autism, may present as a preoperative behavioral management problem. Administration of intramuscular ketamine 2 to 3 mg/kg is occasionally required in this patient population to facilitate parental separation and mask induction of anesthesia or intravenous (IV) line placement.

Children with trisomy 21 have inherently smaller upper airways, tonsillar hypertrophy, and frequent OSA. Upper airway obstruction during inhalation induction of general anesthesia is common and is probably caused by a combination of a large tongue, large adenoidal and tonsillar tissue, an abnormally small pharynx, and hypotonia of the pharyngeal dilator muscles. Almost always, placement of an oral airway device provides satisfactory relief of the obstruction.

Children with trisomy 21 have an increased incidence of tracheal anomalies, which are more likely in the presence of congenital heart disease. Therefore whenever tracheal intubation is performed, one should ensure that the endotracheal tube is not too large, and that the endotracheal tube is normally positioned above the carina.

Lower airway anomalies are also common in children with trisomy 21. These include tracheomalacia and bronchomalacia, which predispose to intrathoracic tracheal and bronchial collapse during forced expiration, and extrathoracic tracheal collapse during forced inspiration. Pulmonary abnormalities may also occur in this population.

One of the most important anesthetic considerations in children with trisomy 21 is the potential presence of atlantoaxial instability (AAI). Children with trisomy 21 tend to have generalized ligamental laxity, which includes the transverse ligament that holds the dens of the axis (C2) in place against the posterior surface of the anterior arch of the atlas (C1) ( Fig. 9.2 ). Normally, this ligament holds the dens tightly against the anterior arch of the atlas to facilitate rotatory neck motion, and maintains cervical stability during flexion, extension, and side-bending of the neck. However, when the ligament is lax, the dens may separate from the anterior arch of the atlas and encroach upon the spinal cord during motion away from the neutral position.

There have been a number of reported cases of children with trisomy 21 who exhibited new signs and symptoms of spinal cord damage upon awakening from general anesthesia or sedation, presumed because of excessive neck movement while unconscious. Most pediatric centers do not require preoperative cervical radiographs but assume that all children with trisomy 21 may be susceptible to AAI while sedated or anesthetized. The head and neck should be kept in as neutral a position as clinically feasible, and it should be documented in the anesthesia record that these safety precautions were observed. For example, during myringotomy and tube insertion, the child’s body can be turned along with the neck while the tubes are being placed; during tonsillectomy, instead of neck extension, the table can be placed in the Trendelenburg position.

Approximately 40% of children with trisomy 21 have congenital heart disease, including (in descending order of incidence) atrial septal defect, ventricular septal defect, tetralogy of Fallot, and endocardial cushion defects. Pulmonary hypertension may occur in up to 5% patients with trisomy 21, even in the absence of heart disease. Optimization of cardiac status is essential before elective surgery, and prophylaxis against infective endocarditis may be necessary. Bradycardia during sevoflurane induction occurs often in children with trisomy 21, even in the absence of structural heart disease. Although unsubstantiated, it appears that resting heart rates during sevoflurane anesthesia seem to be lower in this population.

Additional medical problems in children with trisomy 21 that may impact anesthetic management include obesity, immunodeficiency, hypothyroidism, autism, hearing and vision deficits, epilepsy, and moyamoya disease, to name a few. An exaggerated response to atropine has been reported but has not been clinically proven. Children with trisomy 21 do not have different analgesic requirements.