Trisomy 18 (Edwards), Trisomy 13 (Patau)

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Lelia Hope Adamson, a happy 26-month old with Trisomy 18.
(image provided with permission from her parents)

 

Introduction

 

Trisomy 18 and Trisomy 13 are the only two live born trisomies apart from trisomy 21 (Down syndrome). The first case reports of these syndromes only began to appear in the literature in 1960. These trisomy disorders tend to have much more severe clinical manifestations than trisomy 21, and only rarely do affected infants survive to one year of life. Mean survival time (MST) for trisomy 18 is 14.5 days, and MST for trisomy 13 is 7 days (Rasmussen et al.,2003; Duarte et al., 2004). A recent paper evaluating the in hospital care of infants with trisomy 18 and trisomy 13 nationally demonstrates that a substantial number of these patients are living longer than 1 year of life (Nelson et al, 2011). 

 

A characteristic constellation of clinical findings that suggest a specific diagnosis exist for both trisomies 13 and 18, with cardiac defects typically being more severe in trisomy 13. Since some of these patients may be mosaics for the trisomy cell line, a variety of phenotypic expression is possible.

 


 

Trisomy 18

 

Epidemiology

Trisomy 18, or Edwards Syndrome, is the second most common trisomy behind Down syndrome. This syndrome has an incidence of between 1 in 3000 and 1 in 8000, with a 3:1 Female:Male predominance. 90% of cases of trisomy 18 are due to maternal nondisjunction. 10% of cases are due to mosaicism, and less than 1% of cases are due to a translocation.

 

Clinical Diagnosis

Trisomy 18 typically presents with some combination of the following features:

  1. Clenched hand, with overlap of the 2nd and 5th fingers, over the 3rd and 4th
  2. Intrauterine growth retardation (IUGR)
  3. Rocker bottom feet
  4. Micrognathia, prominent occipital, micro-ophthalmia
  5. Low set ears
  6. Cardiac defects, such as ventricular septal defect (VSD), atrial septal defect (ASD) and patent ductus arteriosus (PDA)
  7. "Strawberry shaped" calvarium
  8. Generalized muscle spasticity
  9. Renal anomalies
  10. Mental retardation

 

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Photo of an infant with characteristic features of Trisomy 18 - clenched hand with finger overlap, rocker bottom feet, micrognathia, low set ears

 

 

Genetic Diagnosis

Trisomy 18 is confirmed by karyotype with FISH analysis.

 

Prognosis

Trisomy 18 is associated with severe mental retardation and severe failure to thrive. 50% of patients die by one week of life, and 90% of patients die by one year of life.

 


Trisomy 13

 

Epidemiology

Trisomy 13, or Patau syndrome, is the least common of the live-born trisomy disorders, with an incidence of 1 in 5000 to 1 in 2,000 live births. There is an equal distribution between affected males and affected females. 75% of trisomy 13 cases are due to maternal nondisjunction, 20% of cases are due to a translocation, and 5% of cases are due to mosaicism.

 

The major midline dysmorphic features of trisomy 13 are due to a defect in the fusion of the midline prechordial mesoderm in the first three weeks of gestation. Trisomy 13 tends to present with more severe craniofacial and midline defects than are found in Trisomy 18 or 21. 

 

Clinical Diagnosis

Trisomy 13 traditionally presents with some combination of the following clinical features:

  1. Holoprosencephaly
  2. Polydactyly
  3. Seizures
  4. Deafness
  5. Microcephaly
  6. Midline Cleft Lip
  7. Midline Cleft palate
  8. Abnormal ears
  9. Sloping forehead
  10. Cutis aplasia ("punched out lesions" of the scalp)
  11. Omphalocele
  12. Cardiac and renal anomalies
  13. Mental retardation

 

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Typical features of an infant with Trisomy 13.  A.  Midline defect with cleft lip & palate.  B.  Clenched hand with overlapping fingers.  C. Postaxial polydactyly.  D. Equinovarus deformity.  E. Punched out aplasia cutis scalp lesions.  From http://health-7.com

 

Genetic Diagnosis

Trisomy 13 is confirmed by karyotype with FISH analysis.

 

Prognosis

The prognosis of patients diagnosed with Trisomy 13 remains poor. 85% of Trisomy 13 newborns die before reaching one year of age, and only six cases have been described in the literature as surviving past the age of 10 years (Iliopoulos et al.). 44% of these patients die within 1 month, and > 70% die within one year. Iliopoulos et al. have hypothesized that factors associated with longer survival largely pertain to the absence of cardiac abnormalities and holoprosencephaly; Rasmussen et al. have also demonstrated that the general rate of survival is higher for female Trisomy 13 patients when compared with males.

  


Management

The vast majority (98%) of pregnancies diagnosed with trisomies 13 and 18 have traditionally been terminated (Gessner et al., 2003), but there has recently been an increase in the number of families who decide to continue with the pregnancy. Sibiude et al. recently described the perinatal care of 34 fetuses diagnosed with trisomies 13 and 18 in utero. Of these, 14 pregnancies (41%) were continued, with four eventually being delivered alive; only two of these neonates survived long enough (10 and 11 days) to receive intensive care in the neonatal unit.

 

Sibiude et al. emphasized that a highly individualized, interdisciplinary approach should be utilized with families who have been diagnosed with a pregnancy carrying trisomy 13 or trisomy 18. Some families, for example, opted to continue with routine prenatal care, whereas others desire a more customized approach involving more frequent ultrasound surveillance of the pregnancy. Those patients who continued with pregnancies also expressed a desire to hear the fetal heart during subsequent prenatal visits. The majority of families who underwent a live birth expressed a to see the newborn alive, albeit briefly.

 

It is important to determine the level of postpartum intervention that is desired by parents following delivery; Sibiude et al. encourage using prenatal visits to discuss both the birthing process and likely appearance of the child with parents. Vaginal deliveries with intermittent monitoring of fetal heart rates are preferred, as this mode of delivery allows for immediate contact between the parents and child. Cesarean sections are strongly discouraged, as they are of little benefit to both the neonate and mother, with exceptions being made for scenarios in which an obstetric indication for a Cesarean section is present. Unstable live deliveries should largely be provided comfort care, such as oxygen and analgesia. Neonates who are stable following intensive care should be discharged home with the parents and a full plan for support in place.

 

Finally, an interdisciplinary approach should be utilized in these situations, with support provided by genetic counselors, pediatric cardiologists, obstetricians, and clinical geneticists in addition to social work support.

 

Ethics

As was noted in the introduction, many more infants with trisomy 18 and trisomy 13 are surviving longer than 1 year of age (Nelson et al, 2011). The utilization of a multidisciplinary approach has resulted in more infants undergoing medical and surgical procedures as part of their treatment; the age at hospitalization of 36% of these infants with trisomy 18 and trisomy 13 was over 1 year of age (Nelson et al, 2011).  

 

This raises yet more ethical issues in terms of the risk, benefit and futility of the variety of interventions that may be possible in prolonging these infants & children's lives, and requires an open, honest.  Multidisciplinary involvement with support from a medical ethicist in addition to the family and care team is strongly encouraged.  As with all care, it should be individualized, compassionate, and with the best interests of the child and minimization of pain and suffering in mind.

 

Support Resources

Support groups for families can be invaluable when facing a pre or post-natal diagnosis of trisomy 18 or 13.  Enlist the help of a social worker within the genetics department for additional resources, but here are some parent-run support organizations that can be helpful for families during this difficult time.

 

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Support Organization for Trisomy - 18, 13 and related disorders.  Provides information & support for families, medical professionals in the US & Internationally.  Website also available in Spanish.

 

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Parent support for those expecting, caring or remembering a child with Trisomy 18, as well as support for friends and family, and those having a child after Trisomy 18.

 

 

References:

  1. Brewer. CM. Survival in trisomy 13 and trisomy 18 cases ascertained from population based registers. Journal of Medical Genetics. 2002; 39(9): 54.
  2. Cotran. Robbins Pathologic Basis of disease. 6th Ed. 1999. WB Saunders. 168-176.
  3. Duarte AC, Menezes AIC, Devens ES, Roth JM, Garcias GL, Martino-Roth MG. Patau syndrome with a long survival. A case report. Genetics and Molecular Research. 2004; 3(2): 288-92.
  4. Fuloria, M. The Newborn Examination I: Emergencies and Common Abnormalities Involving the Skin, Head, Neck, Chest, and Respiratory and Cardiovascular Systems. American Family Physician. 2002; 65(1): 61-68.
  5. Gessner BD. Reasons for trisomy 13 or 18 despite the availability of prenatal diagnosis and pregnancy termination. Early Human Development. 2003; 73: 53-60.
  6. Hill, L. The Sonographic Detection of Trisomies 13, 18, and 21. Clinical Obstetrics and Gynecology. 1996; 39(4): 831-850.
  7. Iliopoulous D, Sekerli E, Vassiliou G, Sidiropoulou V, Topalidis A, Dimopoulou D, Voyiatzis N. Patau syndrome with a long survival (146 months): a clinical report and review of literature. American Journal of Medical Genetics. 2005; 140(1): 92-3.
  8. Rasmussen SA, Wong LYC, Yang Q, May KM, Friedman JM. Population-based analyses of mortality in trisomy 13 and trisomy 18. Pediatrics. 2003; 111(4): 777-784
  9. Siberry, G. and Iannone, R. Ed. The Harriet Lane Handbook. 16th Ed. 2002. Mosby. 278-279.
  10. Nelson KE, Hexem KR, Feudtner C. Inpatient hospital care of children with trisomy 13 and trisomy 18 in the United States. Pediatrics 2012;129:869-876.

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