Nursing Care of Infants and Children With Congenital Heart Disease and Associated Genetic Conditions

Lauren T. Cobert


Pediatr Nurs. 2019;45(2):75-85. 

In This Article

Charge Syndrome


CHARGE syndrome is an autosomal dominant genetic syndrome caused by a mutation in the CHD7 gene (Hudson, Trider, & Blake, 2017; Jones, Campo, & Jones, 2013). CHARGE is a mnemonic that stands for Coloboma, Heart defects, choanal Atresia, Retardation of growth and development, Genital hypoplasia, and Ear anomalies (Hsu et al., 2014). The incidence rate is variable, with estimates ranging from 0.6 to 1 in 10,000 live births (Hefner & Fassi, 2017). Many features of CHARGE syndrome can be attributed to disruption of neural crest cell migration in the fetus at weeks 4 through 6 post-fertilization (Hsu et al., 2014; Schulz et al., 2014).

Most cases of CHARGE syndrome are caused by sporadic de novo pathogenic variants in the CHD7 gene on chromosome 8q12, although cases of autosomal dominant familial transmission have also been reported (Burns Wechsler & McDonald, 2018; Chen, 2017; Hartshorne, Stratton, & van Ravenswaaij-Arts, 2011; Online Mendelian Inheritance in Man [OMIM], n.d.). CHD7 mutations are predominantly single-nucleotide variants, with 44% being nonsense, 34% frame shift, 11% splice site, and 8% missense (Basson & van Ravenswaaij-Arts, 2015; van Ravenswaaij-Arts, Blake, Hoefsloot, & Verloes, 2015).

Clinical Features

Meticulous physical assessment may reveal many anomalies associated with CHARGE syndrome. Examination should focus on the face, external ears, and cranial nerves (Bergman et al., 2011). Coloboma presentation varies depending on which part of the eye is affected and can result in photophobia, retinal detachment, and/or vision loss (Hsu et al., 2014). Cardiac defects are present in up to 85% of affected individuals (Fahed, Gelb, Seidman, & Seidman, 2013). Tetralogy of Fallot, double outlet right ventricle, atrioventricular septal defects, aortic arch anomalies, and patent ductus arteriosus are the most common cardiac defects associated with CHARGE syndrome (Corsten-Janssen & Scambler, 2017; OMIM, n.d.). Neonates and young infants up to 6 weeks of age are obligate nose breathers, and those with choanal atresia will exhibit respiratory distress and cyanosis that worsens with feeding and improves with crying. Other signs of choanal atresia include the inability to pass a nasogastric tube into the nasopharynx and chronic unilateral nasal blockage or discharge (Allen, 2012).

Infants with CHARGE syndrome are typically normal size at birth, and delayed growth does not usually manifest until late infancy (Kaplan & Hudgins, 2008). Growth hormone deficiency may also occur (Trider, Arra-Robar, van Ravenswaaij-Arts, & Blake, 2017). Cryptorchidism can be identified if one or both testes are not palpable in the scrotum. Hypogona trophic hypogonadism is manifested by a micropenis in males. The characteristic outer ears may be small, low-set, asymmetric, cup- or lop-shaped, with decreased cartilage and a triangular concha (Hudson et al., 2017). Normally, infants ages 0 to 3 months will startle or cry in response to a loud sound, and infants older than 4 months will turn their head in response to sound; an infant who does not do this should raise suspicion for hearing loss (Ball, Dains, Flynn, Solomon, & Stewart, 2014). Hypo plastic semicircular canals are observed in more than 95% of patients with CHARGE syndrome but is unusual in the other syndromes considered in the differential diagnosis (Hefner & Fassi, 2017).

Another prominent feature of CHARGE syndrome is cranial nerve dysfunction, which is present in 90% of individuals (Hudson et al., 2017). Abnormalities of cranial nerves I, VII, VIII, IX, and X can cause anosmia, facial palsy, sensorineural hearing loss, swallowing problems, and aspiration, respectively (Hudson et al., 2017). Children with CHARGE syndrome have characteristic facies of a square face, broad forehead, broad nasal bridge and columella, and flat midface (Hsu et al., 2014). Phenotypic features of CHARGE syndrome are displayed in Figure 1.

Figure 1.

Phenotypic Features of CHARGE Syndrome


CHARGE syndrome is a clinical diagnosis based on major and minor criteria (Blake et al., 1998; Verloes, 2005). The major criteria of CHARGE syndrome include coloboma, choanal atresia, and/or characteristic ear anomalies (Chen, 2017). A neonate or infant with at least one of the major features of CHARGE syndrome in conjunction with other anomalies should prompt further evaluation (Burns Wechsler & McDonald, 2018; Hefner & Fassi, 2017). Differential diagnosis for CHARGE syndrome includes 22q11.2 deletion syndrome, VACTERL association, Goldenhar syndrome, and Kabuki syndrome (Corsten-Janssen et al., 2013; Corsten-Janssen & Scambler, 2017).

Genetic testing may occur prenatally or postnatally via CHD7 analysis and/or by chromosomal microarray analysis (CMA), also known as comparative genomic hybridization (aCGH) (Bergman et al., 2011; Hartshorne et al., 2011; Hefner & Fassi, 2017; Lalani, Hefner, Belmont, & Davenport, 2012; van Ravenswaaij-Arts et al., 2015; van Ravenswaaij-Arts & Martin, 2017). It is important to note that roughly 10% of children with a clinical diagnosis of CHARGE syndrome have normal CHD7 mutation analysis results (Basson & van Ravenswaaij-Arts, 2015). Conversely, CHARGE syndrome has a broad phenotypic spectrum and patients who do not meet full clinical criteria should not be excluded from CHD7 testing (Bergman et al., 2011; Hartshorne et al., 2011).

A full workup for CHARGE syndrome should include a complete blood cell count with differential; serum calcium level; CT scan or MRI of the brain, temporal bone/mastoid, choanae, and inner ears; dilated eye examination; echocardiogram; renal ultrasound; otoacoustic emissions and auditory brainstem response hearing tests; and swallowing studies (de Geus et al., 2017; Mehr, Hsu, & Campbell, 2017; van Ravenswaaij-Arts et al., 2015).


Long-term care of patients with CHARGE syndrome includes management by pediatric subspecialists in genetics, cardiology, endocrinology, gastroenterology, otolaryngology, speech-language therapy (SLT), occupational therapy (OT), physical therapy (PT), ophthalmology, psychology, and dentistry (Trider et al., 2017). Patients with CHARGE syndrome are medically complex, and require numerous surgeries and invasive testing throughout childhood. Close monitoring of growth and pubertal development is essential in patients with CHARGE syndrome. Hypogonatrophic hypogonadism should be diagnosed early so that hormone replacement therapy can be initiated at the appropriate prepubertal age to prevent delayed puberty and osteoporosis (Bergman et al., 2011; Trider et al., 2017). Hearing and vision impairment may require the use of cochlear implants or bone-anchored hearing aids (van Ravenswaaij-Arts & Martin, 2017). Communication skills must be optimized through speech therapy. Motor delay can occur due to hypoplastic semicircular canals (Choo, Tawfik, Martin, & Raphael, 2017). Balance and vestibular problems can cause mobility issues, and children may require assistive devices for mobility and ambulation, as well as vestibular rehabilitation therapy (Choo et al., 2017; van Ravenswaaij-Arts & Martin, 2017). Feeding difficulties are common throughout childhood, necessitating the need for swallowing studies, parental nutrition, and enteral tube feedings (Macdonald, Hudson, Bladon, Ratcliffe, & Blake, 2017). Once in school, patients with CHARGE syndrome will likely qualify for special education through an Individualized Education Program (IEP). Patients with CHARGE syndrome may also develop problematic behaviors, and many children will receive a psychiatric diagnosis of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and/or obsessive-compulsive disorder (OCD) (Hartshorne et al., 2011).