Edwards' Syndrome

Trisomy 18 It is Edwards' syndrome and not Edward's syndrome as it is named after JH Edwards.

It is a rare congenital disorder caused by an extra number 18 chromosome instead of the usual pair. Mosaics can occur in which some cells are normal with 46 chromosomes and others have the extra one. The mosaic variations tend to be less severely affected. In some variations there are only 46 chromosomes but an extra one is fused to another. This is called translocation.

The incidence is given as 1 in 3,000 births but may be falling due to antenatal screening and selective termination of pregnancy. A very large study from Denmark gave an incidence of just in excess of 1 in 7,000 between 1977 and 1986.¹ Of the viable trisomies, this syndrome is less common that Down's syndrome but more common than Patau's syndrome.
Girls are affected 3 times as often as boys but there is evidence from early testing that this may be due to a greater tendency for boys with this condition to abort.²

A personal or close family history of giving birth to an affected child increases the risk. Risk rises with rising maternal age.³ This is less marked than for Down's syndrome (trisomy 21) but more marked than Patau's syndrome (trisomy 13).

The following may occur in the prenatal period:

• Polyhydramnios possibly due to defective sucking and swallowing reflexes
• Oligohydramnios due to renal defects
• Small placenta
• Single umbilical artery
• Intrauterine growth retardation
• Weak fetal activity
• Fetal distress

The following may be noted after birth:

• Low birth weight
• Low set ears
• Micrognathia (small jaw)
• Clenched hands
• Hypoplastic finger nails
• Microcephaly (small head and brain)
• Severe learning disability
• Umbilical or inguinal hernia
• Diastasis recti
• Cryptorchism
• Heart defects including atrial septal defect, ventricular septal defect and patent ductus arteriosus.
• Renal abnormalities including horseshoe kidney, hydronephrosis and polycystic kidneys.
• Coloboma of iris
• Pectus carinatum (short sternum).

Edwards' syndrome and Patau's syndrome can look very similar.

Chromosome analysis will confirm the diagnosis. Parents should also have chromosome analysis in case of balanced translocation although the risk to subsequent pregnancies seems small. Balanced translocation is when there is fusion of two chromosomes,or joining end on end but if the total number of chromosomes is counted it appears to be 45 and the total amount of genetic material is normal. Full trisomy occurs in more than 95% of cases, mosaicism in 5% and translocation is very rare.

A study from Leicester³ looked at 44 cases of Patau's Syndrome (trisomy 13) and 88 cases of Edward's Syndrome (trisomy 18) and found that 64% of cases were diagnosed because chromosome screening was done after concerns raised by fetal anomaly scanning in the 2nd trimester. In only 3% of cases concern was raised from the abnormalities of the blood screening for Down's Syndrome. In 11% of cases the diagnosis was not made until birth. Hence anomaly scanning is the best method of screening. In a study from Northwick Park, 33% of Down's syndrome, 68% of Edwards' syndrome and 52% of Patau's syndrome were diagnosed before 28 weeks without the use of serum screening. ⁴ A second trimester anatomical screening by ultrasound appears to be a good method of detection.⁵It is possible to screen for Edwards syndrome using maternal blood markers, to give a detection rate of 76% with a false positive rate of 0.5%⁶ but the value of this in the general population is dubious.

This is a catastrophic experience for the parents who will need a great deal of support and counselling including a risk assessment for future pregnancy. It may help to put them in touch with others who can give support and information. Soft.UK (Support Organisation for Trisomy) gives such support to families affected by all the trisomy syndromes. Its website is listed at the end.
Screening should be offered for future pregnancies. For full trisomy, the risk of recurrence in a future pregnancy is less than 1%.⁷
Treatment of the child is supportive but life sustaining measures are not recommended. Considerable thought and discussion is recommended before undertaking measures such as surgical correction of abnormalities. Nasogastric or gastrostomy feeding is feasible but it is questionable if this is prolonging life or prolonging death.
For those who do survive beyond a year, medical and surgical management provides a very difficult problem.⁸

80% die in the first week and few survive beyond a few months although there are 10 documented cases of survival to the teens but with very severe handicap. The median length of survival is 6 days.¹ About 5 to 10% survive beyond a year.

• Newborns have a 40% chance of surviving to age 1 month.
• Infants have a 5% chance of surviving to age 1 year.
• Children have a 1% chance of surviving to age 10 years.

Trisomy 18 was described by Edwards et al⁹ in April 1960 and by Smith et al¹⁰ in September 1960. It was John Edwards who gained the eponym. The latter paper included Klaus Patau amongst the authors. He had described trisomy 13 earlier that year.¹¹