Edwards syndrome

Trisomy 18
Chromosome 18

Trisomy 18 or Edwards Syndrome is a genetic disorder caused by the presence of all or part of an extra 18th chromosome. It is named after John H. Edwards, who first described the syndrome in 1960. It is the most common autosomal trisomy, after Down Syndrome, that carries to term.

Trisomy 18 is caused by the presence of three — as opposed to two — copies of chromosome 18 in a fetus or infant's cells. The incidence of the syndrome is estimated as one in 3,000 live births. 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.

Prognosis

The survival rate of Edwards Syndrome is very low. About 95% die in utero. Of liveborn infants, only 50% live to 2 months, and only 5–10% will survive their first year of life. Major causes of death include apnea and heart abnormalities. It is impossible to predict the exact prognosis of an Edwards Syndrome child during pregnancy or the neonatal period. Because major medical interventions are routinely withheld from these children, it is difficult to determine what the survival rate or prognosis would be with aggressive medical treatment. The median life span is five to fifteen days. One percent of children born with this syndrome live to age ten, typically in cases of the less severe mosaic Edwards syndrome.

Incidence/prevalence

The rate of occurrence for Edwards Syndrome is approximately one in 3,000 (for conception) and approximately one in 6,000 (for live births), as 50% of those diagnosed prenatally with the condition will not survive the prenatal period. Although women in their 20s and 30s may conceive Edwards Syndrome babies, there is an increased risk of conceiving a child with Edwards Syndrome as a woman's age increases, with the average age for this disorder being 32½.

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 part (such as due to translocations). The additional chromosome usually occurs before conception. The effects of the extra copy vary greatly among people, depending on the extent of the extra copy, genetic history, and chance. Edwards syndrome occurs in all human populations, but is more prevalent in females.

A healthy egg or sperm cell contains individual chromosomes — one to contribute to each of the 23 pairs of chromosomes needed to form a normal cell with typical human karyotype of 46 chromosomes. Numerical errors arise at either of the two meiotic divisions and cause the failure of segregation of a chromosome into the daughter cells (non-disjunction). This results in an extra chromosome making the haploid number 24 rather than 23. Fertilization of these eggs or sperm that contain an extra chromosome results in trisomy, or three copies of a chromosome rather than two.

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 now 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 people have two copies of chromosome 18, plus extra material from chromosome 18 attached to another chromosome. With a translocation, the person has a partial trisomy for chromosome 18 and the abnormalities are often less than for the typical Edwards syndrome.

Features and characteristics

Infants 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, mental retardation, developmental delays, growth deficiency, feeding difficulties, breathing difficulties, and arthrogryposis (a muscle disorder that causes multiple joint contractures at birth).

Some physical malformations associated with Edwards syndrome include: a 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, underdeveloped thumbs and or nails, absent radius, webbing of the second and third toes, clubfoot or Rocker bottom feet, and undescended testicles in males.

In utero, the most common characteristic is cardiac anomalies, followed by central nervous system anomalies such as head shape abnormalities. The most common head shape anomaly is the presence of choroid plexus cysts, which is a pocket of fluid on the brain that is not problematic in itself but may be a marker for Trisomy 18. Sometimes excess amniotic fluid or polyhydramnios is exhibited.