Trisomy 18

Trisomy 18, Edwards Syndrome
Classification and external resources
Chromosome 18
ICD-10	Q91.0-Q91.3
ICD-9	758.2
DiseasesDB	13378
eMedicine	ped/652

Trisomy 18 (T18) (also known as Trisomy E 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.^[1] It is the second 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^[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.

Prognosis

In England and Wales, there were 495 diagnoses of Edwards’ syndrome (trisomy 18), of which 92% were made prenatally. There were 339 terminations, 49 stillbirths/miscarriages/fetal deaths, 72 unknown outcomes, and 35 live births.^[3] Because approximately 3% of cases of Edwards’ syndrome 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). Only 50% of liveborn infants live to 2 months, and only 5–10% survive their first year of life. Major causes of death include apnea and heart abnormalities. It is impossible to predict the exact prognosis of a child with Edwards syndrome during pregnancy or the neonatal period. ^[4] The median lifespan is 5–15 days.^[5][6] One percent of children born with this syndrome live to age 10, typically in less severe cases of the mosaic Edwards syndrome.^[4]

Incidence/prevalence

Edwards syndrome occurs in approximately 1 in 3,000 conceptions and approximately 1 in 6,000 live births; 50% of those diagnosed with the condition prenatally will not survive the prenatal period. 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.^[7][8]

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.^[4]

A healthy egg 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.^[9]

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.

Features and characteristics

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

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).^[10][11]

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; underdeveloped thumbs and or nails absent radius, webbing of the second and third toes; clubfoot or Rocker bottom feet; and in males, undescended testicles.^[10][11]

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 is a pocket of fluid on the brain that is not problematic in itself but may be a marker for Trisomy 18.^[12][13] Sometimes excess amniotic fluid or polyhydramnios is exhibited.^[10]

See also

• 18q deletion syndrome

References

External links

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