Edwards syndrome

Definition

Edwards' syndrome is caused by an extra (third) copy of chromosome 18. The extra chromosome is lethal for most babies born with this condition. It causes major physical abnormalities and severe mental retardation. Very few children afflicted with this syndrome survive beyond the first year.

Description

Edwards' syndrome is associated with the presence of a third copy of chromosome number 18. Humans normally have 23 pairs of chromosomes. Chromosomes are numbered 1–22, and the 23rd pair is composed of the sex chromosomes, X and Y. A person inherits one set of 23 chromosomes from each parent. Occasionally, a genetic error occurs during egg or sperm cell formation. A child conceived with such an egg or sperm cell may inherit an incorrect number of chromosomes. In the case of Edwards' syndrome, the child inherits three (trisomy), rather than two, copies of chromosome 18. Ninety-five percent of the children are full trisomies, 2 percent are due to translocations, where only part of an extra chromosome is present (this may be hereditary), while 3 percent are mosaic trisomies, where the extra chromosome is present in some but not all of the cells.

Edwards' syndrome is usually fatal, with most babies dying before birth. Of those who do make it to birth, 20–30 percent die within one month. However, a small number of babies (less than 10 percent) live at least one year.

Edwards' syndrome is also referred to as trisomy 18, trisomy E, and trisomy 16–18. It is the second most common trisomy, after trisomy 21 (Down syndrome).

Demographics

Edwards' syndrome occurs in approximately one in every 5,000 live births and one in every 5,000 stillborn births; it affects girls more often than boys. Women older than their early thirties have a greater risk of conceiving a child with Edwards' syndrome, but it can also occur with younger mothers.

Causes and Symptoms

Most children born with Edwards' syndrome appear weak and fragile, and they are often underweight. The head is unusually small and the back of the head is prominent. The ears are malformed and low-set, and the mouth and jaw are small (micrognathia). The baby may also have a cleft lip or cleft palate. Frequently, the hands are clenched into fists, and the index finger overlaps the other fingers. The child may have clubfeet, and toes may be webbed or fused.

Numerous problems involving the internal organs may be present. Abnormalities often occur in the lungs and diaphragm (the muscle that controls breathing), and blood vessel malformations are common. Various types of congenital heart disease, including ventricular septal defect (VSD), atrial septic defect (ASD), or PDA (patent ductus arteriosus), may be present. The child may have an umbilical or inguinal hernia, malformed kidneys, and abnormalities of the urogenital system, including undescended testicles in a male child (cryptochordism).

When to Call the Doctor

A child with Edwards' syndrome is likely to have many medical and development needs. Parents should develop good working relationships with their doctor, other specialists, and therapists, and should consult them as needed.

If a woman gives birth to a child with Edwards' syndrome and plans to have another child, a doctor as well as a genetic counselor should be consulted so that prenatal screening and genetic counseling can be conducted.

Diagnosis

Edwards' syndrome at birth may be diagnosed by the physical abnormalities characteristic to the syndrome. Physical examination of the infant may show arched type finger print patterns, while x rays may reveal a short breast bone (sternum). Definitive diagnosis is achieved through karyotyping, which involves drawing the baby's blood for a microscopic examination of the chromosomes. Using special stains and microscopy, individual chromosomes are identified, and the presence of an extra chromosome 18 is revealed.

Edwards' syndrome can be detected before birth. If a pregnant woman is older than 35, has a family history of genetic abnormalities, has previously conceived a child with a genetic abnormality, or has suffered earlier miscarriages, she may undergo tests to determine whether her child carries genetic abnormalities. Potential tests include maternal serum alpha-fetal protein analysis or screening, ultrasonography, amniocentesis, and chorionic villus sampling.

In addition, a pregnant woman carrying a child with Edwards' syndrome may have an unusually large uterus during pregnancy, due to the presence of extra amniotic fluid (polyhydramnios). An unusually small placenta may be noted during the birth of the child.

Treatment

There is no cure for Edwards' syndrome. Since babies with Edwards' syndrome frequently have major physical abnormalities, doctors and parents face difficult choices regarding treatment. Abnormalities can be treated to a certain degree with surgery, but extreme invasive procedures may not be in the best interests of an infant whose lifespan is measured in days or weeks. Medical therapy often consists of supportive care with the goal of making the infant comfortable, rather than prolonging life.

However, 5–10 percent of children with Edwards' syndrome do survive past the first year of life, and require appropriate treatment for the many chronic effects associated with the syndrome. Problems with muscle tone and nervous system abnormalities will affect the development of motor skills, possibly resulting in scoliosis (curvature of the spine) and esotropia (crossed eyes). Surgical interventions may be limited by child's cardiac health.

Constipation due to poor abdominal muscle tone is often a life-long problem for babies and children with Edwards' syndrome, resulting in fretfulness, discomfort, and feeding problems. Anti-gas medication, special milk formulas, stool softener medicines, laxatives, and suppositories are all possible treatments that the doctor may recommend to ease the discomfort of gas in the bowels or constipation. An enema should not given to the baby or child because it can deplete electrolytes and alter body fluid composition.

Children with Edwards' syndrome will exhibit severe developmental delays, but with early intervention through special education and therapy programs, they can attain some developmental milestones.

Children with Edwards' syndrome appear to have increased risk of developing a Wilms' tumor, a cancer of the kidney that primarily affects children. Therefore, it is recommended that older infants and children with Edwards' syndrome have a routine ultrasound of the abdominal cavity.

Other illnesses that may affect a child with Edwards' syndrome and that may require treatment include congenital heart disease, pulmonary hypertension, elevated blood pressure, apnea episodes, pneumonias, sinus infections, seizures, urinary tract infections, ear infections, and eye infections. Other abnormalities that may require consideration of medical or surgical intervention include club foot, facial clefts, spina bifida, and hydrocephalus.

Nutritional Concerns

Babies with Edwards' syndrome generally have feeding problems related to difficulties in coordination of breathing, sucking, and swallowing. Many have a weak suck and uncoordinated swallow resulting in choking and sometimes vomiting. Gastroesophageal reflux disease, or GERD (the upward movement of small amounts of stomach contents to the esophagus or throat), aspiration (inhalation or trickle of fluids into the lungs), and oral facial clefts may also contribute to feeding difficulties. The baby should be referred to a feeding specialist to help with feeding problems. The specialist can show the parents how to position the baby's head up, in good body alignment, because a baby with Edwards' syndrome may have hyperextension of the head. This is a common condition that occurs before the baby has developed head control. It results in the elongation of throat muscles, making swallowing more difficult. Because of feeding difficulties, many babies with Edwards' syndrome are fed through a tube inserted through the nose or mouth, down through the esophagus, and into the stomach. Some babies eventually progress to bottle or breastfeeding, while others have a gastrostomy (G-tube) placed abdominally to prevent the trauma of tube insertion. Some children are fed both orally and through the tube.

The baby should be fed with pre-softened preemie nipples and given small amounts frequently. To help prevent reflux, the baby's head should be elevated about 30 degrees or more during feeding and for one to two hours after a feeding. If tolerated, high calories formulas or supplements may be fed to help the baby gain weight.

Prognosis

Most children born with Edwards' syndrome die within their first year of life. The average lifespan is less than two months for 50 percent of the children, and 90–95 percent die before their first birthday. The 5–10 percent of children who survive their first year have severe developmental disabilities. They need support to walk, and learning is limited. Verbal communication is also limited, but they can respond to comforting and can learn to recognize, smile, and interact with caregivers and others, and acquire such skills as rolling over and self-feeding. They will have many physical abnormalities that require constant care as doctors and parents work together to prevent and treat various problems.

Prevention

Most cases of Edwards' syndrome are not hereditary and cannot be prevented. However, parents who have had a child with Edwards' syndrome are at increased risk of having another child with the syndrome.

Parental Concerns

Following the birth of a child with Edwards' syndrome, families may wish to seek counseling regarding the effects on relationships within the family. Many people respond with guilt, fear, or blame when a genetic disorder is manifested within a family. Support groups are good sources of information about Edwards' syndrome and can offer emotional and psychological support.

For those families whose child does survive the first weeks of life, the doctor should review with the parents the expected clinical course of the condition, and prepare a management plan for use when the child goes home. Each case must be considered on an individual basis, and the doctor should acknowledge the personal feelings of the parents, as well as the individual circumstances of each child. The theme of "best interest of the child" helps as a guiding principle in decision-making throughout the life of the child. There will be many challenges associated with the care of a child with Edwards' syndrome. As medical crises occur, parents will face decisions and emotions related to the possibility of the child dying.

See also Atrial septal defect; Congenital heart disease.

Resources

Books

Barnes, Ann M., and John C. Carey. Care of the Infant and Child with Trisomy 18 and 13: Medical Problems, Reported Treatments, and Milestones. Omaha, NE: Munroes-Meyer Institute for Genetics and Rehabilitation, 2000.

Stenson, Carol M., et al. Trisomy 18: A Guidebook for Families. Omaha, NE: Munroes-Meyer Institute for Genetics and Rehabilitation, 2000.

Organizations

Chromosome 18 Registry & Research Society. 7715 Oakridge Drive, San Antonio, TX 78229. (210) 657-4968. Web site: www.chromosome18.org.

Support Organization for Trisomy 18, 13, and Related Disorders (SOFT). 2982 South Union St., Rochester, NY 14624. (800) 716-7638. Web site: www.trisomy.org.

Web Sites

Trisomy 18 Support: Families Caring for Families. Available online at: www.trisomy18support.org.

[Article by: Judith Sims; Julia Barrett]

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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

Edwards syndrome (also known as Trisomy 18 (T18) or Trisomy E) 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.

Edwards syndrome is caused by the presence of three – as opposed to two – copies of chromosome 18 in a fetus's or infant's cells. Edwards' syndrome occurs in around one in 6,000 live births and around 80 per cent 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.

Contents 1 Signs and symptoms 2 Genetics 3 Prognosis 4 Epidemiology 5 See also 6 References 7 External links

Signs and symptoms

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).^[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 is a pocket of fluid on the brain that is not problematic in itself but 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 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 England and Wales, there were 495 diagnoses of Edwards syndrome (trisomy 18) in 2008/2009, of which 92% were made prenatally. There were 339 terminations, 49 stillbirths/miscarriages/fetal deaths, 72 unknown outcomes, and 35 live births.^[9] 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). 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.^[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 born with this syndrome survive longer than 1 year,^[13] 1% of children live to age 10, typically in less severe cases of the mosaic Edwards syndrome.^[7] The small percentage of babies with the full Edwards syndrome who survive birth and early infancy may live to adulthood, and children with mosaic or partial forms of this trisomy may have a completely different and much more hopeful prognosis.^[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

1. ^ "Edwards syndrome (John Hilton Edwards)". WhoNamedIt.com. http://www.whonamedit.com/synd.cfm/3438.html. Retrieved 2008-07-24. 
2. ^ ^{a b c} "Health: Edwards syndrome". BBC. http://www.bbc.co.uk/health/physical_health/conditions/edwardssyndrome2.shtml. Retrieved 2012-01-04. 
3. ^ ^{a b c} "What is Trisomy 18?". Trisomy 18 Foundation. http://www.trisomy18.org/site/PageServer?pagename=parents_whatisT18. Retrieved 2008-07-24. 
4. ^ ^{a b} "Trisomy 18". Medline. http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/001661.htm. Retrieved 2008-07-24. 
5. ^ Hurt K, Sottner O, Záhumenský J, et al. (2007). "[Choroid plexus cysts and risk of trisomy 18. Modifications regarding maternal age and markers]" (in Czech). Ceska Gynekol 72 (1): 49–52. PMID 17357350. 
6. ^ Papp C, Ban Z, Szigeti Z, Csaba A, Beke A, Papp Z (2007). "Role of second trimester sonography in detecting trisomy 18: a review of 70 cases". J Clin Ultrasound 35 (2): 68–72. doi:10.1002/jcu.20290. PMID 17206726. 
7. ^ ^{a b c} Chen, MD, Harold. "Introduction to Trisomy 18". EMedicine. http://www.emedicine.com/ped/topic652.htm#section~Introduction. Retrieved 2008-07-24. 
8. ^ For a description of human karyotype see Mittleman, A. (editor) (1995). "An International System for Human Cytogenetic Nomeclature". http://www.iscn1995.org/. Retrieved 2006-06-04. 
9. ^ "National Down Syndrome Cytogenetic Register Annual Reports 2008/09". http://www.wolfson.qmul.ac.uk/ndscr/. 
10. ^ "Trisomy 18: MedlinePlus Medical Encyclopedia". Nlm.nih.gov. 2011-12-14. http://www.nlm.nih.gov/medlineplus/ency/article/001661.htm. Retrieved 2012-01-04. 
11. ^ Rodeck, Charles H.; Whittle, Martin J. (1999). Fetal Medicine: Basic Science and Clinical Practice. Elsevier Health Sciences. ISBN 044305357X. http://books.google.com/?id=0BY0hx2l5uoC&pg=PA555&dq=Trisomy+18#PPA555,M1. 
12. ^ Zoler, Mitchel L. (March 1, 2003). "Trisomy 13 survival can exceed 1 year". OB/GYN News. http://findarticles.com/p/articles/mi_m0CYD/is_5_38/ai_98830102. Retrieved 2008-07-24. 
13. ^ "Trisomy 13 survival can exceed 1 year | OB/GYN News". Find Articles. 2003-03-01. http://findarticles.com/p/articles/mi_m0CYD/is_5_38/ai_98830102/. Retrieved 2012-01-04. 
14. ^ [1]
15. ^ "Edwards' Syndrome | Doctor | Patient UK". Patient.co.uk. 2011-03-02. http://www.patient.co.uk/doctor/Edward%27s-Syndrome.htm. Retrieved 2012-01-04. 
16. ^ "Prevalence and Incidence of Edwards Syndrome". Diseases Center-Edwards Syndrome. Adviware Pty Ltd.. 2008-02-04. http://www.wrongdiagnosis.com/e/edwards_syndrome/prevalence.htm. Retrieved 2008-02-17. "mean maternal age for this disorder is 32½" 

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

v d e Pathology: chromosome abnormalities (Q90–Q99 · 758) Autosomal Trisomies Down syndrome (21) · Edwards syndrome (18) · Patau syndrome (13) Trisomy 9 · Trisomy 8/Warkany syndrome 2 (8) · Trisomy 22/Cat eye syndrome (22) · Trisomy 16 Monosomies/deletions 1q21.1 deletion syndrome/1q21.1 duplication syndrome/TAR syndrome (1) · Wolf-Hirschhorn syndrome (4) · Cri du chat/Chromosome 5q deletion syndrome (5) · Williams syndrome (7) · Jacobsen syndrome (11) · Miller–Dieker syndrome/Smith–Magenis syndrome (17) · DiGeorge syndrome (22) · 22q13 deletion syndrome (22) genomic imprinting (Angelman syndrome/Prader–Willi syndrome (15)) Distal 18q-/Proximal 18q- X/Y linked Monosomy Turner syndrome (XO) Trisomy/tetrasomy, other karyotypes/mosaics Klinefelter's syndrome (47,XXY) · 48,XXYY · 48,XXXY · 49,XXXYY · 49,XXXXY Triple X syndrome (47,XXX) · 48,XXXX · 49,XXXXX 47,XYY · 48,XYYY · 49,XYYYY 46,XX/XY Translocations Leukemia/lymphoma Lymphoid Burkitt's lymphoma t(8 MYC;14 IGH) · Follicular lymphoma t(14 IGH;18 BCL2) · Mantle cell lymphoma/Multiple myeloma t(11 CCND1:14 IGH) · Anaplastic large cell lymphoma t(2 ALK;5 NPM1) · Acute lymphoblastic leukemia Myeloid Philadelphia chromosome t(9 ABL; 22 BCR) · Acute myeloblastic leukemia with maturation t(8 RUNX1T1;21 RUNX1) · Acute promyelocytic leukemia t(15 PML,17 RARA) · Acute megakaryoblastic leukemia t(1 RBM15;22 MKL1) Other Ewing's sarcoma t(11 FLI1; 22 EWS) · Synovial sarcoma t(x SYT;18 SSX) · Dermatofibrosarcoma protuberans t(17 COL1A1;22 PDGFB) · Myxoid liposarcoma t(12 DDIT3; 16 FUS) · Desmoplastic small round cell tumor t(11 WT1; 22 EWS) · Alveolar rhabdomyosarcoma t(2 PAX3; 13 FOXO1) t (1 PAX7; 13 FOXO1) Other Fragile X syndrome · Uniparental disomy · XX male syndrome

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