Nursing Care of Infants and Children With Congenital Heart Disease and Associated Genetic Conditions.
This article illustrates assessment findings and management of three genetic disorders associated with CHD: CHARGE syndrome, 22q11.2 deletion syndrome, and VACTERL association. Each disorder will be described by its etiology/genetics, clinical features, diagnosis, management, and implications for nursing care. Table 1 defines common dysmorphology terminology used throughout the text.
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).
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.). Neo nates 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. Hypogonatrophic hypogonadism is manifested by a micropenis in males. The characteristic outer ears may be small, lowset, 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). Hypoplastic 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.
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).
22q11.2 Deletion Syndrome
22q11.2 deletion syndrome (22q11. 2DS) is also known by the acronym CATCH, which stands for Cardiac anomalies, Abnormal facies, T cell deficit/Thymic hypoplasia, Cleft palate, and Hypocalcemia (Burn, 1999; Wilson, Burn, Scambler, & Goodship, 1993). It is now recognized that a 22q11.2 deletion is the cause of several syndromes, including DiGeorge syndrome (de la Chapelle, Herva, Koivisto, & Aula, 1981; DiGeorge, 1965), cardiofacial syndrome (Cayler, 1969; Giannotti, Digilio, Marino, Mingarelli, & Dallapiccola, 1994), conotruncal anomaly face syndrome (Takao syndrome) (Burn et al., 1993; Kinouchi, Mori, Ando, & Takao, 1976; Matsuoka et al., 1994; Takao, Ando, Cho, Kinouchi, & Murakami, 1980), velocardiofacial syndrome (Shprintzen syndrome) (Driscoll et al., 1993; Shprintzen et al., 1978), and cases of autosomal dominant Opitz G/BBB syndrome (McDonald-McGinn et al., 1995; Opitz, Frias, Gutenberger, & Pellet, 1969; Opitz, Summitt, & Smith, 1969). Estimated incidence of 22q11.2DS is 1 in 4,000 live births, making it second only to trisomy 21 as the leading cause of developmental delay and major CHD (Bassett et al., 2011).
Most congenital abnormalities associated with 22q11.2DS can be attributed to an embryologic disruption in the development of the pharyngeal arches, which give rise to the thymus, parathyroid glands, aortic arch, and craniofacial structures. The majority of 22q11.2 deletion syndrome cases are caused by de novo deletions, but it has an autosomal dominant pattern of inheritance in 6% to 28% of cases, highlighting the importance of genetic counseling for future pregnancies (Chen, 2017; Fahed et al., 2013).
Eighty-five percent of patients with 22q11.2DS present with cardiac defects (Jones et al., 2013). The most common defects are tetralogy of Fallot, truncus arteriosus, interrupted aortic arch type B, ventricular septal defects, and aortic arch anomalies (OMIM, n.d.). Characteristic facies include almond shaped eyes, prominent nose, bulbous nasal tip, small alar base, malar flatness, and asymmetric crying facies (Habel et al., 2014). T cell deficiency is due to thymic hypoplasia or aplasia and affects up to 75% of children with 22q11.2DS (Chen, 2017). Cleft palate and velopharyngeal incompetence may be repaired surgically usually around 1 year of age, and endotracheal intubation or tracheotomy may be indicated in some cases (Swillen & McDonald-McGinn, 2015). Hypocalcemia due to hypo parathyroidism is most prominent during the neonatal period (Swillen & McDonald-McGinn, 2015). Between one-third to one-half of children with 22q11.2DS will suffer from neurodevelopmental delay, learning difficulties, and psychiatric disorders, such as ADHD, ASD, anxiety disorders, mood disorders, and psychotic disorders (Bassett, Costain, & Marshall, 2017; Jonas, Montojo, & Bearden, 2014; Wenger et al., 2016). Schizo phrenia commonly manifests in adolescence and adulthood (Bassett et al., 2017; Baughman, Morris, Jensen, & Austin, 2015). About onethird of 22q11.2DS patients will have genitourinary abnormalities, such as renal agenesis, dysplastic or cystic kidneys, hydronephrosis, cryptorchidism, hypo spadias, or inguinal hernia (McDonald-McGinn et al., 2015).
Recognition of 22q11.2DS can be difficult due to the wide variability of phenotypic expression. Some children may only present with subtle abnormalities without major cardiac malformations. Physical assessment and identification of the hallmark problems, which include conotruncal cardiac defects, immunodeficiency/chronic infections, palatal abnormalities, feeding and swallowing issues, developmental and/or learning disabilities, and behavioral problems, can assist with diagnosis (Bassett et al., 2011). Red flags in neonates and infants include nasal regurgitation with feeding, hypernasal crying, tetany and seizures, recurrent otitis media and upper respiratory infections, delayed infantile milestones, and poor growth (Bassett et al., 2011). Children and adolescents may present with characteristic facial features, autoimmune diseases, speech and learning delays, psychiatric illnesses, short stature, and thyroid disease (Bassett et al., 2011; Friedman, Rienstein, Yeshayahu, Gothelf, & Somech, 2016).
Diagnosis may be suspected prenatally by single-nucleotide polymorphism-based non-invasive prenatal testing (Gross et al., 2016). Currently 10 U.S. states include severe combined immunodeficiency (SCID) testing in their newborn screening programs, which can identify infants with T cell lymphopenia (Barry et al., 2017; CDC, 2018b). The diagnosis can be confirmed by CMA. Fluorescence in situ hybridization (FISH) has become a less popular testing method due to lower sensitivity and higher cost compared to CMA (Crotwell & Hoyme, 2012; Geddes, Butterly, & Sajan, 2015).
Other investigatory tests include complete blood cell count with differential, immunoglobulin levels, lymphocyte phenotyping, flow cytometry analysis of T cells, autoantibody testing, serum calcium level, thyroid function tests, renal ultrasound, vision and hearing examinations, chest X-ray, echocardiogram, and brain MRI (Chen, 2017).
A multidisciplinary approach to the management of 22q11.2DS includes specialists in genetics, cardiology, gastroenterology, allergy, immunology, plastic surgery, endo crinology, otolaryngology, audiology, SLT, OT, PT, psychology, and psychiatry. Vigilant monitoring and treatment of hypocalcemia and vitamin D supplementation are needed, especially in the neonatal period and during times of biologic stress (i.e., childbirth, acute illness, postoperatively). Some 22q11.2DS patients will have true thymus aplasia and absence of T cells, or complete DiGeorge syndrome, and may require irradiated blood for blood transfusions to avoid graft-versus-host disease, avoidance of live vaccines, antipneumocystis and antifungal prophylaxis, respiratory syncytial virus prophylaxis, immuno globulin treatment, and thymic or peripheral blood T cell transplantation (Allen, 2012; Hofstetter et al., 2014; Maggadottir & Sullivan, 2013). Young children may struggle with motor, speech, and expressive language delays, necessitating the need for early intervention with speech-language, occupational, and physical therapies (Habel et al., 2014). All children with 22q11.2DS should have an educational evaluation for an IEP. It is recommended that all patients with 22q11.2DS undergo psychological evaluation at an early age with continued surveillance throughout their lifetimes (Fung et al., 2015; Swillen & McDonald-McGinn, 2015; Wenger et al., 2016).
VATER association is a sporadic, non-random association of congenital anomalies that includes Vertebral defects, Anal atresia, Tracheoesophageal fistula, Esophageal atresia, and Renal dysplasia (Quan & Smith, 1973). The definition was later expanded to include Cardiac defects and Limb/radial defects, termed VACTERL association (Nora & Nora, 1975; Temtamy & Miller, 1974). Hydrocephalus has also been added to the acronym (VACTERL-H) (Evans, Stranc, Kaplan, & Hunter, 1989). The etiology is unclear, and 90% of cases appear to be sporadic (Jones et al., 2013). The estimated incidence rate is 1.6 in 10,000 live births (Chen, 2017). VACTERL appears to be more common in children with Fanconi anemia and in children born to mothers with diabetes (Stevenson & Hunter, 2013). Between 5% to 33% of patients with Fanconi anemia have VACTERL (Alter & Giri, 2016; Alter & Rosenberg, 2013). Signs and symptoms of Fanconi anemia include skin pigmentation abnormalities, delayed growth, and microcephaly (Jones et al., 2013).
There is strong evidence that VACTERL association is heterogenous. Several signaling pathways and gene families have been implicated in VACTERL, including the Sonic Hedgehog signaling pathway and the HOX gene clusters (Reutter & Ludwig, 2013). A few reports have described an increased prevalence of component features among first-degree relatives of VACTERL patients (Bartels et al., 2012; Solomon, Pineda-Alvarez, Raam, & Cummings, 2010).
Vertebral anomalies, often accompanied by rib anomalies, are present in 60% to 95% of patients with VACTERL association (Chen et al., 2016). Vertebral defects have a wide array of presentation, including scoliosis, butterfly vertebrae, absent vertebrae, vertebral fusions, tethered spinal cord, and sacral agenesis/dysgenesis (Solomon et al., 2014). Of VACTERL patients, 55% to 90% have anal atresia with or without fistula (Solomon, 2011). Other anorectal malformations are also seen, such as imperforate anus, as well as accompanying genitourinary anomalies, including hypo spadias, cryptorchidism, cloacal malformations, and hydrocolpos (Solomon et al., 2014). Cardiac defects appear in 40% to 80% of children with VACTERL (Solomon, 2011). The most common congenital heart defects seen with VACTERL are atrial septal defects, ventricular septal defects, tetralogy of Fallot, transposition of the great arteries, and patent ductus arteriosus (OMIM, n.d.). Tracheo esophageal fistula (TEF) with or without esophageal atresia is also very common (OMIM, n.d.). Structural renal anomalies include renal agenesis, cystic or dysplastic kidneys, duplicated collecting system, horseshoe kidney, renal atrophy or hypoplasia, ectopic kidney, and ureteral/urethral anomalies (Chen, 2017; Cunningham et al., 2014). Non-structural renal problems may also occur, specifically vesicoureteral reflux and hydronephrosis (Cunningham et al., 2014). Limb defects include radial dysplasia or aplasia, hand deviation, preaxial polydactyl, syndactyl, and rudimentary or absent thumb (Kaplan & Hudgins, 2008). Single umbilical artery is also a common finding (Jones et al., 2013). Most children with VACTERL do not have dysmorphic facial features, growth deficiencies, or neurocognitive impairments (Kaplan & Hudgins, 2008). Phenotypic features of VACTERL are displayed in Figure 2.
Neurologic examination should include assessment of reflexes, muscle tone, and tactile stimulation (Solomon et al., 2014). Children with VACTERL association may complain of neck and back pain, and physical assessment of the spine may reveal scoliosis, kyphosis, or lordosis (Solomon et al., 2014). Anal atresia and imperforate anus will be recognized in the immediate postnatal period by meconium ileus or by the inability to insert a rectal temperature probe, but anorectal stenosis may present later with signs of bowel obstruction (Solomon, 2011). TEF may present with signs of inability to pass a nasogastric tube, dysphagia, choking, and reflux (Jones et al., 2013). TEF may also be recognized by an absent gastric bubble on X-ray (England, Eradi, Murthi, & Sutcliffe, 2017). Renal anomalies may not be apparent until imaging is done, but signs include nephrolithiasis, urinary tract infections, and declining renal function (Cunningham et al., 2014).
No definitive diagnostic test is available for VACTERL, so diagnosis is exclusionary and based on the presence of clinical features (Solomon, 2011). Criteria for diagnosis vary among clinicians, but generally the diagnosis is made if three or more defects are present (Chen, 2017; OMIM, n.d.; Solomon et al., 2012). Prenatal ultrasound may detect renal malformations, TEF, cardiac defects, and single umbilical artery (Debost-Legrand et al., 2015), which should prompt testing via CMA (Solomon et al., 2012). Chromosome breakage testing should be considered in patients with suspected Fanconi anemia, which has a primarily autosomal recessive pattern of inheritance and a 25% recurrence risk (Alter & Rosenberg, 2013).
A full workup for VACTERL association may include radiographs of the chest, limbs, abdomen, vertebral column, sacrum, and pelvis; cranial ultrasound; spinal ultrasound, MRI, or CT scan; echocardiogram; abdominal and renal ultrasounds; and voiding cystourethrogram (Cunningham et al., 2013, 2014; England et al., 2017; Oral et al., 2012; Solomon et al., 2014).
Children with VACTERL association require care from pediatric subspecialists in genetics, cardiology, orthopedics, neurosurgery, general surgery, plastic surgery, gastroenterology, and urology. The immediate postnatal period will be centered on surgical correction of life-threatening congenital defects (i.e., TEF, structural cardiac defects, and imperforate anus/anal atresia). Special considerations must be taken for operative procedures (OrphanAnesthesia, 2014). Surgery for anal atresia will require a staged repair with a diverting colostomy until a pull-through procedure can be done. Other sequalae of VACTERL association will require lifelong management. Depending on the defect and severity, limb and spinal problems may either be managed medically or require surgical correction. Dysphagia, gastroesophageal reflux, tracheomalacia, recurrent respiratory infections, nephrolithiasis, urinary tract infections, and renal scarring are common long-term issues (Raam, Pineda-Alvarez, Hadley, & Solomon, 2011). Constipation, incontinence, and functional stooling problems can lead to hospitalizations for complications and poor quality of life due to social isolation (Raam et al., 2011). Bowel problems should ideally be managed at a specialty clinic that cares for children with anorectal continence issues. Although most children with VACTERL association are of normal intelligence, some may require a Section 504 plan for school accommodations.
Understanding the cardiac and extra-cardiac anomalies that accompany CHARGE syndrome, 22q11.2 deletion syndrome, and VACTERL association can have a profound impact on the medical management and outcomes of infants and children diagnosed with these defects. Children with CHD already risk poor neurodevelopmental outcomes, and a cooccurring genetic condition can independently confer an additive negative effect on this (Wernovsky & Licht, 2016). When a major congenital anomaly like CHD is diagnosed, it should raise suspicion for additional congenital anomalies. Nursing assessment of pediatric patients should always incorporate a dysmorphology examination, with a focus on the child's growth and development, behavior, general appearance, head, face, hands and feet, skeletal structures, genitalia, and anus. Pediatric nurses should feel empowered to perform detailed assessments, report abnormalities to the multidisciplinary team, and advocate for appropriate referrals and therapies. Obtaining a detailed family history upon hospital admission/clinic visit is just one method nurses can use to identify appropriate candidates for referral to genetic services (Calzone, Jenkins, Culp, Caskey, & Badzek, 2014).
Pediatric nurses are encouraged to actively engage in genomic research and education. There is a wide variety of genetic resources available on the Internet. Table 2 contains a list of selected articles and websites that can be especially useful at point of care. Nurses and healthcare organizations should also work to integrate genomic competencies into bedside practice because this has the potential to stratify risk, optimize patient outcomes, and ultimately, improve patient quality/duration of life (Calzone, Jenkins, Culp, & Badzek, 2018; Jenkins et al., 2015). The Essentials is the gold standard for practicing nurses to achieve competency in genomics (Consensus Panel on Genetic/Genomic Nursing Competencies, 2009). Additionally, nurses can support patients and families with education, resources, and anticipatory guidance specific to these conditions, as outlined in Table 3.
22q11.2 Society. (n.d.). 22q11.2 Society. Retrieved from http://www.22qsociety.org/
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Allanson, J.E., Biesecker, L.G., Carey, J.C., & Hennekam, R.C.M. (2009). Elements of morphology: Introduction. American Journal of Medical Genetics Part A, 149A(1), 2-5. doi:10.1002/ajmg.a.32601
Allanson, J.E., Cunniff, C., Hoyme, H.E., McGaughran, J., Muenke, M., & Neri, G. (2009). Elements of morphology: Standard terminology for the head and face. American Journal of Medical Genetics Part A, 149A(1), 6-28. doi:10.1002/ajmg.a.32612
Allen, T. (2012). CHARGE syndrome: Diagnosis and clinical management in the NICU. Advances in Neonatal Care, 12(6), 336-342. doi:10.1097/ANC.0b013e318276c320
Alter, B.P., & Giri, N. (2016). Thinking of VACTERL-H? Rule out Fanconi anemia according to PHENOS. American Journal of Medical Genetics Part A, 170(6), 1520-1524. doi:10.1002/ajmg.a.37637
Alter, B.P., & Rosenberg, P.S. (2013). VACTERL-H association and Fanconi anemia. Molecular Syndromology, 4(1-2), 87-93. doi:10.1159/000346035
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Ball, J.W., Dains, J.E., Flynn, J.A., Solomon, B.S., & Stewart, R.W. (2014). Seidel's guide to physical examination (8th ed.). St. Louis, MO: Elsevier/Mosby.
Barry, J.C., Crowley, T.B., Jyonouchi, S., Heimall, J., Zackai, E.H., Sullivan, K.E., & McDonald-McGinn, D.M. (2017). Identification of 22q11.2 deletion syndrome via newborn screening for severe combined immunodeficiency. Journal of Clinical Immunology, 37(5), 476-485. doi:10.1007/s10875-017-0403-9
Bartels, E., Jenetzky, E., Solomon, B.D., Ludwig, M., Schmiedeke, E., Grasshoff-Derr, S.,... Zwink, N. (2012). Inheritance of the VATER/VACTERL association. Pediatric Surgery International, 28(7), 681-685. doi:10.1007/s00383-012-3100-z
Bassett, A.S., Costain, G., & Marshall, C.R. (2017). Neuropsychiatric aspects of 22q11.2 deletion syndrome: Considerations in the prenatal setting. Prenatal Diagnosis, 37(1), 61-69. doi:10.1002/pd.4935
Bassett, A.S., McDonald-McGinn, D.M., Devriendt, K., Digilio, M.C., Goldenberg, P., Habel, A.,... Vorstman, J. (2011). Practical guidelines for managing patients with 22q11.2 deletion syndrome. The Journal of Pediatrics, 159(2), 332-339.e1. http://doi.org/10.1016/j.jpeds.2011.02.039
Basson, M.A., & van Ravenswaaij-Arts, C. (2015). Functional insights into chromatin remodelling from studies on CHARGE syndrome. Trends in Genetics, 31(10), 600-611. doi:10.1016/j.tig.2015.05.009
Baughman, S.T., Morris, E., Jensen, K., & Austin, J. (2016). Disclosure of psychiatric manifestations of 22q11.2 deletion syndrome in medical genetics: A 12-year retrospective chart review. American Journal of Medical Genetics Part A, 167A(10), 2350-2356. doi:10.1002/ajmg.a.37190
Bergman, J.E., Janssen, N., Hoefsloot, L.H., Jongmans, M.C., Hofstra, R.M., & van Ravenswaaij-Arts, C.M. (2011). CHD7 mutations and CHARGE syndrome: The clinical implications of an expanding phenotype. Journal of Medical Genetics, 48(5), 334-342. doi:10.1136/jmg.2010.087106
Biesecker, L.G., Aase, J.M., Clericuzio, C., Gurrieri, F., Temple, I.K., & Toriello, H. (2009). Defining morphology: Hands and feet. American Journal of Medical Genetics Part A, 149A(1), 93-127. doi:10.1002/ajmg.a.32596
Blake, K.D., Davenport, S.L., Hall, B.D., Hefner, M.A., Pagon, R.A., Williams, M.S.,... Graham, J.M., Jr. (1998). CHARGE association: An update and review for the primary pediatrician. Clinical Pediatrics, 37(3), 159-173. doi:10.1177/000992289803700302
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Calzone, K.A., Jenkins, J., Culp, S., & Badzek, L. (2018). Hospital nursing leadership-led interventions increased genomic awareness and educational intent in Magnet settings. Nursing Outlook, 66(3), 244-253. doi:10.1016/j.outlook.2017.10.010
Calzone, K.A., Jenkins, J., Culp, S., Caskey, S., & Badzek, L. (2014). Introducing a new competency into nursing practice. Journal of Nursing Regulation, 5(1), 40-47.
Carey, J.C., Cohen, M.M., Jr., Curry, C.J., Devriendt, K., Holmes, L.B., & Verloes, A. (2009). Elements of morphology: Standard terminology for the lips, mouth, and oral region. American Journal of Medical Genetics Part A, 149A(1), 77-92. doi:10.1002/ajmg.a.32602
Cayler, G.G. (1969). Cardiofacial syndrome: Congenital heart disease and facial weakness, a hitherto unrecognized association. Archives of Disease in Childhood, 44(233), 69-75. Retrieved from https://www.nbci.nlm.nih.gov/pmc/articles/PMC2020193/
Centers for Disease Control and Prevention (CDC). (2018a). Data and statistics on congenital heart defects. Retrieved from https://www.cdc.gov/ncbddd/heartdefects/data.html
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CHARGE Syndrome Foundation. (n.d.b). Image of choanal atresia [Photograph]. Retrieved from https://www.chargesyndrome.org/image-of-choanal-artresia/
CHD7.org. (n.d.). CHD7 database. Retrieved from https://molgenis51.gcc.rug.nl/
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Chen, Y., Liu, Z., Chen, J., Zuo, Y. Liu, S., Chen, W.,... Wu, Z. (2016). The genetic landscape and clinical implications of vertebral anomalies in VACTERL association. Journal of Medical Genetics, 53(7), 431-437. doi:10.1136/jmedgenet-2015-103554
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Choo, D.I., Tawfik, K.O., Martin, D.M., & Raphael, Y. (2017). Inner ear manifestations in CHARGE: Abnormalities, treatments, animal models, and progress toward treatments in auditory and vestibular structures. American Journal of Medical Genetics: Part C: Seminars in Medical Genetics, 175(4):439-449
Consensus Panel on Genetic/Genomic Nursing Competencies. (2009). Essentials of genetic and genomic nursing: Competencies, curricula guidelines, and outcome indicators, 2nd edition. Retrieved from https://globalresearchnurses.tghn.org/site_media/media/medialibrary/2016/05/geneticscompetency.pdf
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Lauren T. Cobert, BS, BSN, RN, is a Pediatric Acute Care Nurse Practitioner Student, the University of Pennsylvania, Philadelphia, PA, and a Pediatric Cardiac Intensive Care Nurse, Children's National Medical Center, Washington, DC
Acknowledgments: The author acknowledges the support provided by faculty members and colleagues on this work, with special thanks to Terri Lipman, Jessica Strohm Farber, and Richard James at the University of Pennsylvania, and to Kenneth Rosenbaum and Debra Regier at Children's National Medical Center.
Table 1. Common Dysmorphology Terminology Clinical Sign Definition Butterfly vertebrae Congenital failure of fusion of the lateral halves of the vertebral body due to persistent notochord tissue, giving the appearance of a butterfly on X-ray. Coloboma Congenital failure of fusion of the lateral halves of the vertebral body due to persistent Choanal atresia notochord tissue, giving the appearance of a butterfly on X-ray. Ear, cup ear, or lop The helix and lobule are pushed forward and in ear deformity towards each other (cup ear) or the helical rim is folded over, wrinkled, or tight (lop ear). Ears, low-set Helix's position is below the imaginary horizontal plane that extends from inner canthus of eye to occiput (Ball, Dains, Flynn, Soloman, & Stewart, 2014). Face, square From a frontal view, a broad upper and lower face (Allanson, Cunniff et al., 2009). Forehead, prominent Forward prominence of the entire forehead due to a protruding frontal bone (not the same as front bossing) (Allanson, Cunniff et al., 2009). Horseshoe kidney Kidneys fuse together at base during fetal development. Maxilla, malar flatness Underdeveloped malar process of the maxilla. The malar process is the most medial superior portion of the maxilla (Allanson, Cunniff et al., 2009). Microtia Small ear size. Nasal bridge, prominent Anterior positioning of the nasal root (Hennekam et al., 2009). Nose, bulbous Increased volume and globular shape of the anteroinferior aspect of the nose. May involve the lower third of the nose or just the tip (Hennekam et al., 2009). Nose, prominent Increased distance between subnasale and pronasale (Hennekam et al., 2009). Preaxial polydactyl Extra finger or toe on the medial side of the hand or foot (Kliegman, Stanton, St. Geme, & Schor, 2015). Syndactyl Incomplete separation of the fingers or toes (Kliegman et al., 2015). Table 2. Clinical Resources for Genetic Conditions Category Resource General American Nurses Association (ANA), Genetics and Personalized Medicine (ANA, n.d.) https://www.nursingworld.org/practice-policy/nursing -excellence/ethics/genetics/ Elements of Morphology Series (Allanson, Biesecker, Carey, & Hennekam, 2009; Allanson, Cunniff et al., 2009; Biesecker et al., 2009; Carey et al., 2009; Hall, Graham, Cassidy, & Opitz, 2009; Hennekam et al., 2009; Hennekam, Allanson et al., 2013; Hennekam, Biesecker et al., 2013; Hunter et al., 2009) GeneReviews (Adam et al., 2018) https://www.ncbi.nlm.nih.gov/books/NBK1116/ Genetic and Rare Diseases Information Center (GARD) (GARD, n.d.) https://rarediseases.info.nih.gov/ Online Mendelian Inheritance in Man (OMIM) (OMIM, n.d.) https://www.omim.org/ National Organization for Rare Disorders (NORD) (NORD, n.d.) https://rarediseases.org/ CHARGE (Bergman et al., 2011) syndrome CHD7 Database (CHD7.org, n.d.) https://molgenis51.gcc.rug.nl/ (Trider et al., 2017) 22q11.2 deletion (Bassett et al., 2011; Fung et al., 2015; Habel et syndrome al., 2014) (Hofstetter et al., 2014) VACTERL (OrphanAnesthesia, 2014) association Category Description General Resources on genetics and genomics competency in nursing. Standardized morphology terminology of the head, face, hands and feet, external genitalia, and congenital anomalies. Includes photos and diagrams of dysmorphic features. An online peer-reviewed database of genetic conditions. Includes information on diagnosis, management, and genetic counseling. A database of rare diseases by the National Institutes of Health. A database of human genes and genetic phenotypes. Includes a database of rare diseases, advocacy and policy information, and patient and family resources. CHARGE Includes an algorithm for CHARGE syndrome genetic syndrome testing. An open-access database on CHD7 mutations. Includes a CHARGE syndrome checklist for each age group. 22q11.2 deletion Clinical guidelines for managing patients with syndrome 22q11.2DS. A clinical guideline for live vaccine use in 22q11.2DS. VACTERL A clinical guideline for anesthesia and operative association considerations in patients with VACTERL association. Table 3. Patient and Family Resources for Genetic Conditions Category Resource General Disease InfoSearch (Disease InfoSearch, n.d.) http://www.diseaseinfosearch.org/ CHARGE CHARGE Syndrome Foundation (CHARGE Syndrome syndrome Foundation, n.d.a) https://www.chargesyndrome.org/ 22q11.2 deletion 22q and You Center (Children's Hospital of syndrome Philadelphia, n.d.) https://www.chop.edu/centers-programs/22q-and-you -center 22q11.2 Society (22q11.2 Society, n.d.) http://www.22qsociety.org/ International 22q11.2 Foundation (International 22q11.2 Foundation, n.d.) http://www.22q.org/ VACTERL Esophageal Atresia and Tracheoesophageal Fistula association (EA/TEF) Child and Family Support Connection (EA/TEF Child and Family Support Connection, n.d.) http://www.eatef.org/ Pull-Thru Network (PTN) (PTN, n.d.) http://www.pullthrunetwork.org/ VACTERL Association Support Group (VACTERL Association Support Group, n.d.) http://www.vacterl-association.org.uk/ Category Description General Lists of resources, advocacy and support organizations, and software applications for genetic diseases. CHARGE A foundation committed to providing support for syndrome patients with CHARGE syndrome and families through resources, research, networking, and outreach. 22q11.2 deletion A dedicated 22q11.2DS center at the Children's syndrome Hospital of Philadelphia. A U.K.-based society of researchers and physicians committed to promoting the research, diagnosis, and management of 22q11.2DS. A foundation committed to providing support for 22q11.2DS patients and families through resources, research, networking, and outreach. VACTERL A support network for families of children born with association esophageal atresia and tracheoesophageal fistula. A support network for patients and families affected by congenital anorectal, colorectal, and urogenital disorders. A U.K.-based support group for families affected by VACTERL association.
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