This chapter is dedicated to presenting an approach to evaluating neonates with congenital anomalies and a review of commonly presenting syndromes seen in the nursery. There is likely to be significant overlap with other chapters in this book and cross-referencing is recommended. Following a discussion of some of the more common syndromes seen in neonates, we have included a table of additional syndromes not covered in the text, with particular emphasis on features of the airway and/or the presence of congenital cardiac disease (see Table 10.1).
Cardiac malformations: ASD, atrial septal defect; AV canal, atrioventricular canal; DORV, double outlet right ventricle.; HLHS, hypoplastic left heart syndrome; IAA, interrupted aortic arch; PDA, patent ductus arteriosus; PS, pulmonary stenosis; TA, tricuspid atresia; TGA, transposition of the great arteries; ToF, Tetralogy of Fallot; VSD, ventricular septal defect.
Other: DL, direct laryngoscopy; EA, esophageal atresia; ETT, endotracheal tube; GAGs, glycosaminoglycans; ICP, intracranial pressure; NG, nasogastric; TEF, tracheoesophageal fistula; TMJ, temporomandibular joint.
Chromosomal and Genetic Abnormalities
Trisomy 21 (T21, Down Syndrome). A genetic syndrome resulting from an extra copy of chromosome 21, either through maternal nondisjunction in meiosis I (>90 percent of cases), chromosomal translocation, or abnormal mitosis resulting in mosaicism.
Incidence: T21 is the most common chromosomal abnormality, with an incidence of about 1:700 live births .
Diagnosis: Prenatal diagnosis can be made via cell-free DNA screening for fetal aneuploidy, chorionic villus sampling, or amniocentesis. After birth, diagnosis is based upon clinical features and karyotyping.
Clinical features: Features found in the neonate include a flat facial profile, slanted palpebral fissures, anomalous ears, hypotonia, poor Moro reflex, midphalangeal dysplasia of the fifth finger, a transverse palmar crease, excessive skin at nape of neck, hyperflexibility of joints, and dysplasia of the pelvis . Features involving the airway include: protruding tongue (appears large relative to the hypoplastic midface), subglottic stenosis and narrow tracheal diameter, and obstructive sleep apnea [3,4]. Greater than 40 percent of children with Trisomy 21 have a cardiac defect; atrioventricular canal defects, patent ductus arteriosus, and Tetralogy of Fallot (ToF) are the most common. Patients have immune deficiency and an increased risk of leukemia, including congenital leukemia, which develops within the first three years of life. The skin can be dry and coarse.
Anesthetic considerations: Careful assessment of respiratory and cardiac status is vital. Prepare for a potentially difficult airway due to relative macroglossia, small hypopharynx, and precautions in the case of an unstable cervical spine. A smaller-sized endotracheal tube (ETT) than predicted by age may be indicated due to the risk of subglottic stenosis . Similar considerations apply when planning a nasal tube, as the nasal passages may be smaller. IV access may be difficult, and sterile technique for placement is recommended due to immune suppression. Anesthetic management will be dictated by the presence and status of cardiac disease .
Pharmacologic and other considerations: Atropine may cause pronounced mydriasis and tachycardia. High concentrations of sevoflurane, i.e., during inhalational induction, may precipitate bradycardia .
22q11 Deletions. The 22q11.2 deletions include a spectrum of features including congenital heart disease, hypocalcemia, immune deficiency, palate abnormalities, and abnormal facies. DiGeorge syndrome will be described as a representative example.
DiGeorge is a genetic syndrome with varied phenotypes, most commonly including cardiac outflow tract obstruction, hypoparathyroidism with hypocalcemia, and immune defects due to thymic hypoplasia.
Incidence: 22q11 deletions occur in 1:3000–1:5000 live births. DiGeorge syndrome involves a monoallelic microdeletion at 22q11.2 (DiGeorge syndrome critical region [DGCR]). It is the most frequent gene deletion and, after trisomy 21, the second most common genetic cause of congenital heart disease. Males and females are equally affected .
Diagnosis: Thymic aplasia may be noted during cardiac surgery. This, plus clinical findings (described below), make the diagnosis. CD4+ counts, karyotyping, and fluorescent in situ hybridization (FISH) using probes from within the deletion segment are confirmatory. Abnormal migration of neural crest cells in the fourth week of gestation affects the development of the third and fourth pharyngeal pouches, leading to cardiac defects, abnormal or absent thymus, and hypoparathyroidism .
Clinical features: Neonatal hypocalcemia, cardiac defects, and recurrent infections are the hallmarks of neonatal disease. Hypocalcemia results from parathyroid hypoplasia, and may present as tetany or seizures. Associated cardiac malformations include ToF, type B interrupted aortic arch, truncus arteriosus, double outlet right ventricle, transposition of the great arteries, and ventriculo-septal defects, among others. Immune dysfunction begins in the first six months of life. In up to 60 percent of patients, craniofacial anomalies are present. These include small dysplastic ears, hypertelorism, downward-slanted palpebral fissures, a cupid-bow mouth, cleft palate, midface hypoplasia, micrognathia, and retrognathia. Anomalies of the airway and esophagus can be associated, such as tracheoesophageal fistula, and laryngo-, tracheo-, or bronchomalacia. Hydronephrosis or nephrocalcinosis can be seen [1,6].
Anesthetic considerations: Assess cardiac anatomy and function with echocardiography. Anticipate possible difficult intubation. Check CBC including lymphocyte count, and electrolytes with kidney function; monitor calcium levels throughout the case. Use sterile technique due to immune compromise. If giving blood products, only use CMV-negative, irradiated products (Graft Versus Host Disease [GVHD] can result from donor T-lymphocytes attacking the host’s cells; irradiation reduces this risk) .
Further reference: GeneReviews® – www.ncbi.nlm.nih.gov/books/NBK1523.
Williams-Beuren Syndrome (WBS; 7q11.23 deletion). Growth retardation, cardiovascular anomalies, with characteristic facial appearance and personality are features of this hemizygous continuous gene deletion syndrome.
Diagnosis: A contiguous deletion within the Williams Beuren syndrome critical region (WBSCR), which includes the elastin gene, is present in 99 percent of individuals with the diagnosis. FISH or deletion/duplication testing can detect this deletion.
Clinical features: Distinctive facial features, cardiovascular disease, connective tissue abnormalities, endocrine disorders, and intellectual disability (mild) are hallmarks of the disease. The characteristic “elfin facies” includes a broad forehead, short nose with a broad tip, a wide mouth with full lips, and large cheeks. Mandibular hypoplasia and dental abnormalities may be present. Elastin arteriopathy underlies cardiovascular disease; supravalvular aortic stenosis (SVAS), peripheral pulmonary stenosis, coronary disease, mitral valve prolapse, coarctation of the aorta, and patent ductus arteriosus have been reported. Intracardiac lesions such as ToF and ventricular septal defects also occur. Connective tissue abnormalities that might be present in the neonate include hoarse voice/cry, inguinal and umbilical hernias, plus joint and skin laxity. Hypercalcemia is common in the neonate, which can lead to nephrocalcinosis .
Anesthetic considerations: Patients with WBS have an increased risk of cardiac arrest and sudden death under anesthesia. The incidence of sudden death in WBS (due to all causes), has been estimated at 1/1000 patient-years . It has also been noted that such arrests tend to be refractory to resuscitation . Obtain an ECG and ECHO prior to providing an anesthetic. However, it appears that the severity of SVAS is not a predictor of sudden death . Check for hypercalcemia and manage if present. The anesthetic plan should anticipate a possible difficult airway due to dental abnormalities and mandibular hypoplasia .
Other: The WBSCR is near the gene for the L-type voltage gated calcium channel alpha-2/delta subunit 7q11.23-q21.1 that has been implicated in some forms of malignant hyperthermia (MH) susceptibility. There is one case report of a child developing masseter spasm with halothane without progression to MH, and another report of a child developing an elevated temperature and creatinine phosphokinase (CPK) after general anesthetic with sevoflurane, N2O, and oxygen, that resolved 12 hours after the anesthetic. It is probably best to avoid succinylcholine and be alert to signs of MH if using volatile agents .
Further reference: GeneReviews® – www.ncbi.nlm.nih.gov/books/NBK1249.
Incidence: 1:13 000–1:15 000 live births .
Diagnosis: The definitive diagnosis of CHARGE syndrome requires having all four major features or three major and three minor features (see below).
Clinical features: CHARGE is an acronym for coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, ear anomalies.
Major features: coloboma, choanal atresia or stenosis, cranial nerve dysfunction or anomaly (CN I and VIII particularly frequent), and characteristic ear.
Minor features: genital hypoplasia, developmental delay, cardiovascular malformation (present in 75–85 percent), growth deficiency, orofacial cleft, tracheoesophageal fistula (15–20 percent), distinctive facial features.
Cardiac malformations include atrioventricular canal defects, conotruncal defects (e.g., ToF), aortic arch anomalies, hypoplastic left heart syndrome, and patent ductus arteriosus. Facial features include square face with broad forehead, prominent nasal bridge, flat midface, midface hypoplasia, and micrognathia. Tracheomalacia and subglottic stenosis are occasionally seen.
Anesthetic considerations: Choanal atresia is bilateral in 50 percent of cases and these neonates, as obligate nasal breathers, may present to the operating room for stent placement. Define cardiac anatomy with echocardiography. Anticipate possible difficult mask ventilation and intubation due to micrognathia, midface hypoplasia, and cleft lip and palate. A smaller ETT may be required if subglottic stenosis is present. Patients with CHARGE are at high risk for aspiration due to CN IX and X anomalies ± presence of tracheoesophageal fistulae. The risk of a difficult airway must be weighed against the possibility of aspiration for each patient.
Further reference: GeneReviews® – www.ncbi.nlm.nih.gov/books/NBK1117 and .
Noonan syndrome: A genetic syndrome characterized by short stature, congenital heart defects, and developmental delay. Several genes are implicated: PTPN11, SOS1, RAF1, and KRAS to name the most common.
Incidence: 1:1000–1:2500 live births. Females and males are equally affected .
Diagnosis: The clinical diagnosis is based on the presence of key features. A variety of single gene mutations have been reported in affected individuals, the most common being a mutation in PTPN11 in 50 percent of cases. It has been called “Turner-like syndrome” though the karyotype in Noonan’s syndrome is normal .
Clinical features: Short stature, congenital heart defects, and developmental delay are characteristic. Other important features include broad/webbed neck, abnormal chest shape with pectus carinatum and excavatum, low-set nipples, cryptorchidism in males, characteristic facies (most apparent in newborns and children) include low-set posteriorly rotated ears, vivid blue/green irises, wide-set eyes, epicanthal folds, thick eyelids. Coagulation defects may also be present. The most common cardiac anomalies include pulmonary stenosis, hypertrophic cardiomyopathy, atrial septal defect, ToF, atrioventricular canal defects, and coarctation of the aorta . It has been reported that many patients with Noonan syndrome have a history of abnormal bruising or bleeding. A recent case series of patients with PTPN11 mutations, however, suggests that the rates of actual coagulopathy are lower than initially thought .
Anesthetic considerations: Carefully evaluate for the potentially difficult airway, cervical spine instability, and cardiac abnormalities. A history of abnormal bleeding should be sought and first-line coagulation studies should be obtained.
Other: There are reports that isoflurane can cause tachycardia. Noonan-like features in infancy are seen in King Denborough syndrome (an MH-susceptible disorder) .
Further reference: GeneReviews® – www.ncbi.nlm.nih.gov/books/NBK1124.