Edwards syndrome
Encyclopedia
Trisomy 18 (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. 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. Edwards' syndrome occurs in around one in 6,000 live births and around 80 per cent of those affected are female. The majority of fetuses with the syndrome die before birth. 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.
, 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 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.
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. Sometimes excess amniotic fluid
or polyhydramnios
is exhibited.
, 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.
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.
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.
and heart abnormalities. It is impossible to predict the exact prognosis
of a child with Edwards syndrome during pregnancy
or the neonatal period. Half of infants with this condition do not survive beyond the first week of life. The median
lifespan is 5–15 days. About 8% of infants born with this syndrome survive longer than 1 year, 1% of children live to age 10, typically in less severe cases of the mosaic
Edwards syndrome. 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.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
caused by the presence of all or part of an extra 18th chromosome
Chromosome 18 (human)
125px|rightChromosome 18 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 18 spans about 85 million base pairs and represents about 2.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
. It is named after John H. Edwards
John H. Edwards
John Hilton Edwards was a British medical geneticist. Edwards reported the first description of a syndrome of multiple congenital malformations associated the presence of an extra chromosome. The extra chromosome belonged to the E group of chromosomes which consisted of chromosomes 16, 17 and 18...
, who first described the syndrome in 1960. It is the second most common autosomal
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
trisomy
Trisomy
A trisomy is a type of polysomy in which there are three copies, instead of the normal two, of a particular chromosome. A trisomy is a type of aneuploidy .-Description and causes:...
, after Down Syndrome
Down syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...
, that carries to term.
Trisomy 18 is caused by the presence of three – as opposed to two – copies of chromosome 18
Chromosome 18 (human)
125px|rightChromosome 18 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 18 spans about 85 million base pairs and represents about 2.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
in a fetus' 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. The majority of fetuses with the syndrome die before birth. 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
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 defectVentricular septal defect
A ventricular septal defect is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart.The ventricular septum consists of an inferior muscular and superior membranous portion and is extensively innervated with conducting cardiomyocytes.The membranous...
, atrial septal defect
Atrial septal defect
Atrial septal defect is a form of congenital heart defect that enables blood flow between the left and right atria via the interatrial septum. The interatrial septum is the tissue that divides the right and left atria...
, patent ductus arteriosus
Patent ductus arteriosus
Patent ductus arteriosus is a congenital disorder in the heart wherein a neonate's ductus arteriosus fails to close after birth. Early symptoms are uncommon, but in the first year of life include increased work of breathing and poor weight gain...
), intestines protruding outside the body (omphalocele
Omphalocele
An omphalocele is a type of abdominal wall defect in which the intestines, liver, and occasionally other organs remain outside of the abdomen in a sac because of a defect in the development of the muscles of the abdominal wall.-Presentation:The sac, which is formed from an outpouching of...
), esophageal atresia
Esophageal atresia
Esophageal atresia is a congenital medical condition which affects the alimentary tract. It causes the esophagus to end in a blind-ended pouch rather than connecting normally to the stomach. It comprises a variety of congenital anatomic defects that are caused by an abnormal embryological...
, mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, developmental delays, growth deficiency, feeding difficulties, breathing difficulties, and arthrogryposis
Arthrogryposis
Arthrogryposis, also known as Arthrogryposis Multiplex Congenita, is a rare congenital disorder that is characterized by multiple joint contractures and can include muscle weakness and fibrosis. It is a non-progressive disease...
(a muscle disorder that causes multiple joint contractures at birth).
Some physical malformations associated with Edwards syndrome include small head (microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
) accompanied by a prominent back portion of the head (occiput
Occiput
The occiput is the anatomical term for the posterior portion of the head, in insects the posterior part of those head capsule.-Clinical significance:Trauma to the occiput can cause a basilar skull fracture....
); 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
Ptosis (eyelid)
Ptosis is a drooping of the upper or lower eyelid. The drooping may be worse after being awake longer, when the individual's muscles are tired. This condition is sometimes called "lazy eye", but that term normally refers to amblyopia...
); a short breast bone; clenched hands; choroid plexus cysts; underdeveloped thumbs and or nails, absent radius
Absent radius
Absent radius is a very rare medical condition in which the radius bone is not developed. This results in a typical position of the arm in which the wrist is plantarflexed and radially deviated.-Classification:...
, webbing
Webbed toes
Webbed toes is the common name for syndactyly affecting the feet. It is characterised by the fusion of two or more digits of the feet. This is normal in many birds, such as ducks; amphibians, such as frogs; and mammals, such as kangaroos...
of the second and third toes; clubfoot or Rocker bottom feet; and in males, undescended testicles.
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. Sometimes excess amniotic fluid
Amniotic fluid
Amniotic fluid or liquor amnii is the nourishing and protecting liquid contained by the amniotic sac of a pregnant woman.- Development of amniotic fluid :...
or polyhydramnios
Polyhydramnios
Polyhydramnios is a medical condition describing an excess of amniotic fluid in the amniotic sac. It is seen in 0.2 to 1.6% of pregnancies,,...
is exhibited.
Genetics
Edwards syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 18th chromosomeChromosome 18 (human)
125px|rightChromosome 18 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 18 spans about 85 million base pairs and represents about 2.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
, either in whole (trisomy
Trisomy
A trisomy is a type of polysomy in which there are three copies, instead of the normal two, of a particular chromosome. A trisomy is a type of aneuploidy .-Description and causes:...
18) or in part (such as due to translocations
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
). The additional chromosome usually occurs before conception
Fertilisation
Fertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
. 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.
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
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
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
Nondisjunction
Nondisjunction is the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2. This could arise from a failure of homologous chromosomes to separate in meiosis I, or the failure of sister chromatids to separate during meiosis II or mitosis. The result of this error is a...
). 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.
Trisomy 18 (47,XX,+18) is caused by a meiotic
Meiosis
Meiosis is a special type of cell division necessary for sexual reproduction. The cells produced by meiosis are gametes or spores. The animals' gametes are called sperm and egg cells....
nondisjunction
Nondisjunction
Nondisjunction is the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2. This could arise from a failure of homologous chromosomes to separate in meiosis I, or the failure of sister chromatids to separate during meiosis II or mitosis. The result of this error is a...
event. With nondisjunction
Nondisjunction
Nondisjunction is the failure of chromosome pairs to separate properly during meiosis stage 1 or stage 2. This could arise from a failure of homologous chromosomes to separate in meiosis I, or the failure of sister chromatids to separate during meiosis II or mitosis. The result of this error is a...
, a gamete
Gamete
A gamete is a cell that fuses with another cell during fertilization in organisms that reproduce sexually...
(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
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
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
Mosaic (genetics)
In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...
Edwards syndrome. Very rarely, a piece of chromosome 18 becomes attached to another chromosome (translocated
Chromosomal translocation
In genetics, a chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer. It is detected on...
) 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. 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 apneaApnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...
and heart abnormalities. It is impossible to predict the exact prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
of a child with Edwards syndrome during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
or the neonatal period. Half of infants with this condition do not survive beyond the first week of life. The median
Median
In probability theory and statistics, a median is described as the numerical value separating the higher half of a sample, a population, or a probability distribution, from the lower half. The median of a finite list of numbers can be found by arranging all the observations from lowest value to...
lifespan is 5–15 days. About 8% of infants born with this syndrome survive longer than 1 year, 1% of children live to age 10, typically in less severe cases of the mosaic
Mosaic (genetics)
In genetic medicine, a mosaic or mosaicism denotes the presence of two populations of cells with different genotypes in one individual who has developed from a single fertilized egg...
Edwards syndrome. 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.
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. 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.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