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Trisomy 18

Edwards' Syndrome

Trisomy 18 (Edwards syndrome) is a chromosomal abnormality. It is characterized growth retardation, microcephaly, microphthalmia, ocular hypertelorism, ptosis, microstomia, distinctively clenched fingers and other congenital malformations.


Presentation

In utero, the patients present with heart defects, central nervous system abnormalities (such as skull anomalies and choroid plexuses cyst), weak fetal activity, small placenta, fetal distress, intrauterine growth restriction (IUGR) and excess amniotic fluid (polyhydramnios).

At birth, the baby is usually of low weight. The fists are closed with the index finger overlapping the third digit, and the fifth digit overlapping the fourth. The hips are narrow with limited capability of adduction. The feet are of typical character called rocker bottom feet (abnormal dermatoglyphics).

There are heart problems such as atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA). Among the heart problems, ventricular septal defect (VSD) is the most common. There are also breathing difficulties and intellectual disabilities. Intestinal hernias, feeding problems and ill located anus are the common gastrointestinal manifestations.

There are also genitourinary problems such as small penis or undescended testes in case of male patient. The face is a characteristic with wide palpebral fissures, wide fontanels, elongated skull, drooping eyelids, small head, small jaw, small sternum, double toes, cleft lip and cleft palate. Microcephaly and microganathia may also be present. Ears are low set and fawn like.
There is also short neck, excessive skin folds and marked hypotonia.

Splenomegaly
  • A 59-year-old female presented with pancytopenia and splenomegaly. Bone marrow was normocellular with 30.4% abnormal large lymphoid cells that were positive for CD5, CD19, CD20, HLA-DR and λ chain.[ncbi.nlm.nih.gov]
Multiple Congenital Anomalies
  • Trisomy 18 or Edwards syndrome is a rare chromosomal anomaly, associated with mild to severe intellectual disabilities and multiple congenital anomalies. Trisomies 18 and 13 are lethal, only 5-10% of patients surviving the first year of life.[ncbi.nlm.nih.gov]
  • Bioethical considerations remain important in the care of babies with multiple congenital anomalies.[ncbi.nlm.nih.gov]
  • In this case, we also emphasize the diagnostic power of microarray analysis in detecting the underlying genetic causes for fetuses with multiple congenital anomalies. 2017 Wiley Periodicals, Inc.[ncbi.nlm.nih.gov]
  • Trisomy 18 is a devastating genetic disorder that can be characterized by multiple congenital anomalies. Some of these anomalies have no medical significance, but merely provide clues to suggest the diagnosis.[ncbi.nlm.nih.gov]
  • There is the possibility of good outcome for patients with mosaic trisomy 18, even in the presence of multiple congenital anomalies.[ncbi.nlm.nih.gov]
Low Set Ears
  • During ultrasonographic examination, we discovered that her fetus had several important abnormalities, including a cystic hygroma, craniofacial defects (low-set ears, broad nose), heart defects (single atrium, single ventricle), agenesis of corpus callosum[ncbi.nlm.nih.gov]
  • Symptoms Clenched hands Crossed legs (preferred position) Feet with a rounded bottom (rocker-bottom feet) Low birth weight Low-set ears Mental deficiency Small head ( microcephaly ) Small jaw ( micrognathia ) Underdeveloped fingernails Undescended testicle[web.archive.org]
  • Symptoms Return to top Clenched hands Crossed legs (preferred position) Heart disease (congenital) Hole, split, or cleft in the iris ( coloboma ) Kidney problems Low birth weight Low-set ears Mental deficiency Separation between the left and right side[web.archive.org]
  • Babies born with trisomy 18 can have heart and kidney problems, a small head with low-set ears, a chest with an unusual shape, and crossed legs. They also have severe intellectual disability.[myhealth.alberta.ca]
  • […] and polyhydramnios (excess amniotic fluid), clenched hands, choroid plexus cysts (a pocket of fluid on the brain that is not problematic in itself but may be a marker for Trisomy 18), rocker bottom feet, and delayed growth, micrognathia (small jaw), low-set[web.archive.org]
Skeletal Dysplasia
  • Twin 1 showed subcutaneous edema, pleural effusion, and mesomelic limb shortening, suggestive of lethal skeletal dysplasia (Roberts syndrome). Twin 2 corresponded to 17 weeks menstrual age with no major malformations.[ncbi.nlm.nih.gov]

Workup

Cytogenetic studies are performed to investigate the type of trisomy 18 (full trisomy 18, partial trisomy 18 or mosaic trisomy 18).

The number of platelets and neutrophils should be evaluated especially during the first week of life. Decreased platelets are the most common hematological abnormality in these patients [8].
Abnormal erythrocyte sedimentation rate (ESR) values may indicate infections.

Imaging studies are performed to detect cardiac abnormalities. Echocardiography may also be helpful. Abnormalities of the gastrointestinal tract are detected by barium meal swallow.
Skeletal abnormalities are evaluated by performing full body skeletal radiography.

Liver Biopsy
  • Liver biopsy and chromosomal analysis revealed paucity of intrahepatic bile ducts and Trisomy 18. Extrahepatic biliary atresia was reported in only a few patients with Trisomy 18.[ncbi.nlm.nih.gov]

Treatment

Not much can be done to reduce mortality and morbidity in the patients of trisomy 18. The treatment is supportive. Infections are treated by the use of antibiotics. Cardiac support is provided by pharmacologically or through surgery. The patients’ parents should also be counselled and psychologically supported.

Prognosis

  • Death in these patients usually occurs due to cessation of breathing and heart anomalies.
  • Most of the embryos and fetuses of trisomy 18 result is miscarriage, stillbirth or abortion [5].
  • 50% of those who are born die in the first week of life.
  • The average life span is 15 days.
  • Only 8% live beyond the age of 1 year.
  • With Edward mosaic syndrome a person can live for more than 10 years. There are some cases of long term survival up to the age of 27 years [6] [7].

Etiology

Trisomy 18 incidence increases with the increasing maternal age and there is mostly nondisjunction of maternal chromosome in meiosis phase 2. The average maternal age is 32.5 years.

Epidemiology

  • KEYWORDS: epidemiology; mortality; survival; trisomy 13; trisomy 18[ncbi.nlm.nih.gov]
  • Author information 1 Department of General Pediatrics and Interdisciplinary Medicine, National Center for Child Health and Development, Tokyo, Japan. 2 Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of[ncbi.nlm.nih.gov]
  • […] arthrogryposis (joint contractures) visceral malformations diaphragmatic anomalies renal malformations pulmonary malformations pulmonary lobar anomalies redundant skin folds cryptorchidism spina bifida (6%) scoliosis omphalocele Cantrell pentalogy ( 3232702 ) Epidemiology[humpath.com]
  • Summary Epidemiology Incidence is estimated at between 1/6000 and 1/8000 births. In utero death occurs in more than 95% of fetuses with this chromosome anomaly.[orpha.net]
  • Trisomy 18 Epidemiology Trisomy 18, or Edwards Syndrome, is the second most common trisomy behind Down syndrome.[pedclerk.bsd.uchicago.edu]
Sex distribution
Age distribution

Pathophysiology

With increasing maternal age, the chances of disjunction during meiosis increase. A maternal egg may have an extra pair of chromosome even before conception. After fertilization by a sperm, the egg has 47 chromosomes - two pairs of normal 23 chromosomes and one extra chromosome. These extra chromosomes lead to full trisomy 18 which manifests with full blown defects in the cardiovascular system, renal system and the central nervous system.

In some cases, partial trisomy 18 has been reported. In partial trisomy 18, the main pathology is translocation.

There is also a rare phenomenon of mosaic trisomy 18 in which some cells have an extra chromosome 18 while other cells don’t. There is marked phenotypic variation in such cases [4].

Prevention

The females of reproductive age should be educated regarding the hazards of delayed pregnancy. Regular antenatal visits should be performed by all pregnant females so that any developmental anomaly in the fetus can be identified in utero [9] [10].

Summary

Trisomy 18 is the trisomy of the chromosome 18; i.e. there is an abnormally extra chromosome 18 in addition to the normal pair of chromosome 18. Trisomy 18 is also known as Edward syndrome after the scientist who described it in 1960 [1].

It occurs due to chromosomal disjunction during meiosis phase 2 even before conception. Females are usually more frequently affected as compared to males [2]. Higher incidence of trisomy 18 is seen with increasing maternal age.

Most of the fetuses with this syndrome die in utero. If born, there is multisystem involvement including that of cardiac and central nervous systems. The patient usually has craniofacial and digital abnormalities. Owing to this multisystem involvement, the patients who survive suffer from high morbidity and mortality [3].

Patient Information

Trisomy 18, also called Edward syndrome occurs with increase maternal age. Most of the fetuses die in utero; those who take birth have a multiple system anomalies such as cardiac, renal, Gastro enteral, genitourinary and skeletal abnormalities.

The skeletal abnormalities are obvious when physical exam is done. There are craniofacial and digital abnormalities. Due to multiple system involvement the survival decreases with increasing age. Treatment is supportively. 

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Last updated: 2019-07-11 22:33