TRISOMY 18 (EDWARDS SYNDROME)

Background
Medical Management Considerations
References
Resources for Families
Advisory Committee
Publication Information

Learning Points

• Confirm that Trisomy 18 (Edwards Syndrome) is the second most common trisomy after Down Syndrome.
• Recognize that Trisomy 18 (Edwards Syndrome) has severe physical and intellectual implications and that life expectancy is very limited (~30-50% of affected individuals die within one month of age).
• Restate the occurrence of Trisomy 18 (Edwards Syndrome) (1:3,000-5,000 live births) and acknowledge that it occurs more often in females than in males (4:1).
• Delineate appropriate diagnostic tests both prenatally and postnatally (Prenatal: amniocentesis or chorionic villus sampling and chromosome analysis; Postnatal: fluorescent in situ hybridization (FISH) analysis or bone-marrow karyotype).
• List six characteristic features of Trisomy 18 (Edwards Syndrome): e.g.,
  • Small for gestational age
  • Restricted growth
  • Microcephaly
  • Clenched hands with overlapping fingers
  • Low-set ears
  • Complex congenital heart malformation and defects (95%+)
• Delineate four possible conditions associated with Trisomy 18 (Edwards Syndrome); e.g.,
  • Cerebral Palsy
  • Spina Bifida (5%)
  • Hydrocephalus
  • Hearing deficiency
• Explain why it is important to discuss ethical considerations with the infant’s parents, or to refer them to a hospital ethics committee.
• Refer families to appropriate resources on Trisomy 18 (Edwards Syndrome).

BACKGROUND
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Description

Trisomy 18, the second most common trisomy after Down Syndrome, is a syndrome with severe physical and intellectual implications. Life expectancy is very limited: about 30-50% of affected individuals die within one month of age, and less than 10% survive beyond one year of age. Females are somewhat more likely to survive than males. The genetic cause of this syndrome is nondisjunction resulting in trisomy of chromosome 18 in 90% of cases, mosaicism in 5-10% of cases, and translocation in 1-2% of cases.

Occurrence

• 1:3,000-5,000 live births
• Females > Males 4:1
• Recurrence risk to patient’s siblings: 1%
• The occurrence of trisomy 18 increases with increased maternal age.

Diagnosis

Prenatal: amniocentesis or chorionic villus sampling and chromosome analysis

Postnatal: fluorescent in situ hybridization (FISH) analysis or bone-marrow karyotype

Characteristic Features

• Small for gestational age
• Restricted growth
• Microcephaly
• Clenched hands with overlapping fingers
• Low-set ears
• Complex congenital heart malformation and defects (95%+) (ventricular septal defect, atrial septal defect, patent ductus arteriosus, pulmonary valve stenosis, etc.)
• Esophageal atresia
• Diaphragmatic hernia
• Neural tube defects
• Small mandible with large recessed tongue
• Cleft lip/palate
• Micrognathia
• Short palpebral fissures
• Hypoplastic nails
• Rocker-bottom feet
• Respiratory distress
• Gastric distension
• Feeding difficulties (poor suck/swallow)
• Failure to thrive
• Developmental delays
• Mental retardation (usually severe/profound)

Possible Associations

• Cerebral Palsy
• Spina Bifida (5%)
• Hydrocephalus
• Hearing deficiency
• Ear infections
• Amenorrhea
• Aspiration or airway obstruction
• Gastroesophageal reflux disease
• Seizures (30% in first year)
• Apnea
• Respiratory difficulties (pneumonia, pulmonary hypertension)
• Scoliosis
• Eye abnormalities (10%) (infections, coloboma, esotropia, microphthalmos, corneal opacities)
• Radial aplasia (5-10%)
• Liver abnormalities (hepatoblastoma)
• Kidney defects (Wilms tumor, hydronephrosis)
• Omphalocele
• Urinary tract infection
• Constipation
• High blood pressure
• Sinus infections
• Hypersensitivity to sunlight

MEDICAL MANAGEMENT CONSIDERATIONS
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Note: These considerations are in addition to the normal medical care provided to an individual without trisomy 18. All recommendations can be addressed through clinical examination by the primary care provider, unless otherwise noted.

Because life expectancy is so limited and individuals who survive beyond infancy usually present severe physical and intellectual disabilities, it is important to discuss ethical considerations with the infant’s parents, or to refer them to a hospital ethics committee if possible. In many cases, major surgery may only inflict unnecessary suffering, since life expectancy usually remains very limited. Many parents may conclude that nonintervention is in their child’s best interest. It is equally important to remind parents that 5-10% of children with trisomy 18 do survive the first year of life, and those who do survive usually advance to some degree in their milestones and interact with their families in many ways. Thus, the outlook is not necessarily hopeless. For long-term survivors, many of the early problems become more manageable as physicians, specialists, and parents work together to find appropriate solutions. In any case, it is important to focus on the unique medical circumstances of the child and the personal feelings of his or her parents.

Infancy (Birth to 1 year)

• Perform complete physical and neurological exam to detect congenital anomalies
• Perform chromosome analysis
• Expect to provide full support, including artificial ventilation and endotracheal intubation
• Evaluate cardiac function (echocardigram); refer to pediatric cardiologist as needed
• Discuss option of corrective heart surgery if infant has reasonable chance of living for some time
• Obtain abdominal ultrasound including kidney and liver by 10 months of age, repeating as indicated
• Consider nasogastric tube or gastronomy and closure of tracheoesophageal fistula as needed (or refer to gastroenterologist)
• Assess hearing by 6 months of age (otoacoustic emission (OAE) or brainstem auditory evoked response (BAER))
• Assess vision by a few weeks of age (clinical examination by primary care provider, or refer to opthalmologist)
• Provide genetic counseling, including discussion of recurrence risk
• Refer to early intervention programs and trisomy 18/disability support groups
• Discuss possibility of SSI enrollment

Ongoing (all ages)

• Refer to cardiologist as needed
• Monitor hearing and vision regularly
• Monitor for scoliosis
• Monitor growth
• Refer for physical and occupational therapy evaluation as needed
• Ensure psychological support for parents
• To prevent reflux and aspiration, recommend small, frequent feedings and elevate head during and after feedings
• To prevent constipation, recommend adequate fluid and fiber intake and consider stool softener medication, laxatives and/or suppositories
• Refer to nutritionist as needed

Childhood (1 to 13 years)

• Monitor speech and language progress
• Refer for speech and language therapy evaluation as needed
• Monitor school progress (if applicable)
• Recommend and arrange for dental care (note: children with congenital heart disease should receive antimicrobial prophylaxis before dental procedures)

Adolescence and Adulthood (13 years and over)

• Discuss long-term financial plans
• Discuss alternative community living resources
• Monitor prevocational training and vocational activities
• Discuss community-supported employment opportunities

REFERENCES
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Peer-reviewed Journal Articles/Academies

American Academy of Pediatrics, Committee on Bioethics. (1996). Ethics and the Care of Critically Ill Infants and Children, Pediatrics 98(1), 149-152.

Bos, AP, et al. (1992). Avoidance of Emergency Surgery in Newborn Infants with Trisomy 18. Lancet, 339(8798), 913-915.

Carey, JC. (1992). Health Supervision and Anticipatory Guidance for Children with Genetic Disorders (Including Specific Recommendations for Trisomy 21, Trisomy 18, and Neurofibromatosis I. Pediatric Clinics of North America, 39, 25-53.

Goldstein, H & Nielsen, I.C.G. (1988). Rates and Survival in Individuals with Trisomy 13 and 1, Clinical Genetics, 34, 366-372.

Van Dyke, D.C. & Allen, M. (1990). Clinical Management Considerations in Long-term Survivors with Trisomy 18, Pediatrics, 85, 753-759.

Special Interest Groups/Other Publications

Barnes, A.M, & Carey, J.C. (2006). Common Problems of Babies with Trisomy 18 or 13. Support Organization for Trisomy 18, 13, and Related Disorders. Retrieved on February 28, 2006

Clinical Management of Edwards’ Syndrome (editorial). (1992). Lancet, 339(8798), 904.

Smith, DW. (1988). Trisomy 18 Syndrome. In: Smith’s Recognizable Patterns of Human Malformation (4th ed. p. 16-19). Philadelphia: WB Saunders.

RESOURCES FOR FAMILIES
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California Department of Developmental Services
916-654-1690

California Regional Centers
915-654-1958

The Chromosome 18 Registry and Research Society
210-657-4968

Exceptional Parent Magazine
800-247-8080

March of Dimes Birth Defects Foundation
914-428-7100

Support Organization for Trisomy 18, 13, and Related Disorders (SOFT)
800-716-SOFT

ADVISORY COMMITTEE
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Theodore A. Kastner, M.D., M.S.
Felice Weber Parisi, M.D., M.P.H.
Romie H. Holland, M.D.
Patrick J. Maher, M.D.

PUBLICATION INFORMATION
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This document does not provide advice regarding medical diagnosis or treatment for any individual case, and any opinions or statements contained in this document are not intended to serve as a standard of medical care. Physicians are encouraged to view the considerations presented in this document in light of evolving scientific information. This document is not intended for use by the layperson. Reproduction of this document may be done with proper credit given to California Department of Developmental Services.