Edwards syndrome

Edwards syndrome (also known as Trisomy 18 [T18]) is a genetic disorder caused by the presence of all or part of an extra 18th chromosome. This genetic condition almost always results from nondisjunction during meiosis. It is named after John Hilton Edwards, who first described the syndrome in 1960.^[1] It is the second most common autosomal trisomy, after Down syndrome, that carries to term.

Edwards syndrome occurs in around one in 6,000 live births and around 80 percent of those affected are female.^[2] The majority of fetuses with the syndrome die before birth.^[2] The incidence increases as the mother's age increases. The syndrome has a very low rate of survival, resulting from heart abnormalities, kidney malformations, and other internal organ disorders.

Signs and symptoms

Children born with Edwards syndrome may have some or all of the following characteristics: kidney malformations, structural heart defects at birth (i.e., ventricular septal defect, atrial septal defect, patent ductus arteriosus), intestines protruding outside the body (omphalocele), esophageal atresia, intellectual disability, developmental delays, growth deficiency, feeding difficulties, breathing difficulties, and arthrogryposis (a muscle disorder that causes multiple joint contractures at birth).^[3][4]

Some physical malformations associated with Edwards syndrome include small head (microcephaly) accompanied by a prominent back portion of the head (occiput); low-set, malformed ears; abnormally small jaw (micrognathia); cleft lip/cleft palate; upturned nose; narrow eyelid folds (palpebral fissures); widely spaced eyes (ocular hypertelorism); drooping of the upper eyelids (ptosis); a short breast bone; clenched hands; choroid plexus cysts; underdeveloped thumbs and or nails, absent radius, webbing of the second and third toes; clubfoot or Rocker bottom feet; and in males, undescended testicles.^[3][4]

Clenched hand and overlapping fingers: index finger overlaps third finger and fifth finger overlaps fourth finger, characteristically seen in Trisomy 18.

In utero, the most common characteristic is cardiac anomalies, followed by central nervous system anomalies such as head shape abnormalities. The most common intracranial anomaly is the presence of choroid plexus cysts, which are pockets of fluid on the brain. These are not problematic in themselves, but their presence may be a marker for trisomy 18.^[5][6] Sometimes excess amniotic fluid or polyhydramnios is exhibited.^[3]

Genetics

Edwards syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 18th chromosome, either in whole (trisomy 18) or in part (such as due to translocations). The additional chromosome usually occurs before conception. The effects of the extra copy vary greatly, depending on the extent of the extra copy, genetic history, and chance. Edwards syndrome occurs in all human populations but is more prevalent in female offspring.^[7]

A healthy egg and/or sperm cell contains individual chromosomes, each of which contributes to the 23 pairs of chromosomes needed to form a normal cell with a typical human karyotype of 46 chromosomes. Numerical errors can arise at either of the two meiotic divisions and cause the failure of a chromosome to segregate into the daughter cells (nondisjunction). This results in an extra chromosome, making the haploid number 24 rather than 23. Fertilization of eggs or insemination by sperm that contain an extra chromosome results in trisomy, or three copies of a chromosome rather than two.^[8]

Trisomy 18 (47,XX,+18) is caused by a meiotic nondisjunction event. With nondisjunction, a gamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome 18; the gamete thus has 24 chromosomes. When combined with a normal gamete from the other parent, the embryo has 47 chromosomes, with three copies of chromosome 18.

A small percentage of cases occur when only some of the body's cells have an extra copy of chromosome 18, resulting in a mixed population of cells with a differing number of chromosomes. Such cases are sometimes called mosaic Edwards syndrome. Very rarely, a piece of chromosome 18 becomes attached to another chromosome (translocated) before or after conception. Affected individuals have two copies of chromosome 18 plus extra material from chromosome 18 attached to another chromosome. With a translocation, a person has a partial trisomy for chromosome 18, and the abnormalities are often less severe than for the typical Edwards syndrome.

Prognosis

In 2008/2009, there were 495 diagnoses of Edwards syndrome (trisomy 18) in England and Wales, 92% of which were made prenatally. There were 339 abortions, 49 stillbirths/miscarriages/fetal deaths, 72 unknown outcomes, and 35 live births.^[9] Because approximately 3% of cases with unknown outcomes are likely to result in a live birth, the total number of live births is estimated to be 37 (2008/09 data are provisional). Major causes of death include apnea and heart abnormalities. It is impossible to predict an exact prognosis during pregnancy or the neonatal period.^[7] Half of infants with this condition do not survive beyond the first week of life.^[10] The median lifespan is 5–15 days.^[11][12] About 8% of infants survive longer than 1 year.^[13] One percent of children live to age 10, typically in less severe cases of the mosaic Edwards syndrome.^[7] Parents with surviving children who take part in support groups report that these children enriched their family and their couple irrespective of the length of their lives.^[14]

Epidemiology

Edwards syndrome occurs in approximately 1 in 6,000 live births, but more conceptions are affected by the syndrome because the majority of those diagnosed with the condition prenatally will not survive the prenatal period.^[2][15] Although women in their 20s and early 30s may conceive babies with Edwards syndrome, the risk of conceiving a child with Edwards syndrome increases with a woman's age. The average maternal age for conceiving a child with this disorder is 32½.^[16]

See also

• 18q deletion syndrome

References

External links

• Trisomy 18 Foundation, Inc.
• SOFT USA Support Organization For Trisomy 18, 13, and Related Disorders
• Trisomy 18 Support Program
• Chromosome 18 Clinical Research Center
• SOFT UK Support Organisation for trisomy 13/18 and related disorders
• The Chromosome 18 Registry & Research Society
• Perinatal Hospice Care - Preparing for birth and death"
• Humpath #5389