This chapter highlights the more common genetic disorders that are encountered in acute care practice.
Lynn D. Mohr
A congenital disorder described in 1979 with a characteristic set of congenital features categorized as major, minor, and occasional findings.
Leading cause of congenital deaf-blindness.
70% of children have mutation in the CDH7 gene on chromosome 8.
Autosomal dominant inheritance.
Arrest in embryonic differentiation during the second month of gestation, when the affected organs are in the formative stages.
C: Coloboma of the eye (key-hole-shaped defect seen in eye).
H: Heart defects.
A: Atresia of the nasal choanae.
R: Retardation of growth and/or development.
G: Genital and/or urinary abnormalities.
E: Ear abnormalities and deafness (Figure 20.1).
Differentiate between other syndromes.
VACTERL, 22q11.2 deletion.
Major features (e.g., common in CHARGE syndrome and uncommon in other syndromes/conditions).
Cranial nerve anomalies.
Gene sequencing supports diagnosis.
Congenital heart defect: surgical correction.
Choanal atresia repair.
Kidney function evaluation.
Feeding/nutritional support and gastroesophageal reflux therapy.
Hearing aid/assistive devices.
Hormone replacement for delayed puberty some cases.
More information at CHARGE Syndrome Foundation: retrieved from www.chargesyndrome.org/
DiGeorge Syndrome (22q11.2 Deletion Syndrome)
Deletion of chromos ome 22q11.2.
Most often results from a new mutation, but inherited in 10% of cases.
Inherited through an autosomal dominant pattern from a parent.
Common clinical features exist among DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome because they share a genetic deletion of chromosome 22q11.
Cardiac outflow tract abnormalities (e.g., tetralogy of Fallot, interrupted aortic arch).
Cleft palate with feeding and speech disorders, including velopharyngeal insufficiency.
Conductive hearing loss can occur secondary to cleft palate.
Frequent otitis media.
Absence or hypoplasia of the thymus, resulting in immune deficiency and increased susceptibility to infection.
Hypoplasia of the parathyroid gland, resulting in hypocalcemia.
Cognitive impairment and growth delay; hypotonia is common in infancy.
Skeletal abnormalities (e.g., cervical spine abnormalities, cervical spine instability, polydactyly, club foot).
Vertebral abnormalities (e.g., butterfly vertebrae, hemivertebrae, rib abnormalities).
Renal abnormalities (e.g., absent, cystic, or multicystic kidneys; vesicoureteral reflux).
Fluorescence in situ hybridization (FISH) analysis or comparative genome hybridization (CGH) analysis for a deletion at chromosome 22q11.2 confirms the diagnosis.
Congenital heart defect: surgical correction as indicated.
Cleft palate: surgical correction.
Immune dysfunction therapy: aggressive treatment of infection, avoidance of live vaccines.
Kidney anomalies: ultrasound evaluation.
Calcium replacement as needed.
Annual hearing screening.
Speech and physical therapy.
Cervical spine films at 4 years of age to evaluate for cervical spine abnormalities/instability.
The acronym CATCH-22 is often used to describe the defect: cardiac, abnormal facies, thymic hypoplasia, cleft palate, hypocalcemia resulting from 22q11 deletion.
Fragile X Syndrome
Most common cause of inherited intellectual disability.
Caused by a fragile site on chromosome Xq27.3.
Fragile sites are areas of chromosomes that have a tendency to break, attenuate, or separate under growth.
Males are affected more often and more severely than females.
Facial appearance is characterized by a long face and prominent jaw, forehead, and ears (Figure 20.2).
Macroorchidism may not be present until puberty.
Mild to profound cognitive impairment, autistic behavior, and developmental delays are evident.
Seizures may develop over time.
Poor eye contact, speech delays, hyperactivity, and aggressive tendencies.
Molecular observation of an expanded DNA segment of the FMR1 (fragile X mental retardation 1) gene.
Medical management of seizures, if present.
Early intervention with behavioral therapy, educational evaluation, and support (e.g., speech and occupational therapy).
Autosomal dominant disorder resulting in connective tissue disease affecting the skeletal, cardiovascular, and ocular systems.
Mutation in the fibrillin-1 (FBN1) gene with phenotypic variability of the disorder.
Typically tall and thin with an arm span exceeding the height (Figure 20.3A).
Scoliosis, pectus excavatum, or pectus carinatum can develop.
Dural ectasia, an enlargement of the dura at the lumbosacral level, is common and is usually asymptomatic, but may cause back and leg pain.
Lens displacement (ectopia lentis) often occurs in the first decade of life. Severe myopia may also be present.
Steinberg thumb sign presence: protrusion of distal phalanx of thumb beyond the ulnar border when hand is in clenched fist position (Figure 20.3B).
Associated cardiac complications are progressive aortic root dilation with or without aortic regurgitation, mitral valve prolapse, and mitral regurgitation.
Diagnosis is based on major and minor clinical criteria involving primarily the skeletal, cardiovascular, and ocular systems.
In general, a tall stature or an increased arm span to height ratio is the most consistent presenting finding.
Major criteria include:
Aortic root dilation for age or aortic dissection (Figure 20.4), ectopia lentis, lumbosacral dural ectasia, and skeletal findings.
Prevention of complications and genetic counseling are most important.
Scoliosis and pectus abnormalities are often treated with bracing and/or surgery.
Dural ectasia can be serially followed with magnetic resonance imaging. Symptomatic children may require pain control therapy.
Annual ophthalmologic evaluations to screen for myopia, increased intraocular pressure, lens dislocation, or retinal detachment.
Cardiac, skeletal, and ocular monitoring.
Trisomy 18 (Edwards Syndrome)
Lynn D. Mohr
Chromosomal disorder caused by an additional chromosome 18.
Females are more commonly affected than males.
Higher mortality in newborn period among males compared with females.
95% die before birth, 50% carried to term will be stillborn, <10% will survive to 1 year of age.