Transcript Edwards syndrome

Imad Fadl-Elmula
Nondisjunction
History
Independently described by:
1. Edwards et al., 1960.
2. Smith et al., 1960.
Incidence
Incidence
 Trisomy 18 is the second most common
autosomal trisomy after trisomy 21.
 1 in 6000-8000 live births.
Morbidity
 Approximately 95% of conceptuses with
trisomy 18 die in embryonic or fetal life.
 5-10% of affected children survive beyond
the first year of life.
Race
No racial predilection exists.
Sex
Females compose about 80% of cases.
Age
Trisomy 18 is detectable during the
prenatal and newborn periods.
The high mortality rate is often due to:
1. Cardiac and renal malformations.
2. Feeding difficulties.
3. Sepsis.
4. Apnea caused by CNS defects.
 Trisomy
18 in 95% of cases.
 Mosaicism 46,XY/47,XY,+18
 Translocation trisomy gives rise
to partial trisomy 18 syndrome.
Origin of trisomy
 90%
of trisomies are maternal in origin.
 10% of trisomies are paternal in origin.
 Meiosis II errors occurring twice as
frequently as meiosis I errors.
Mechanisms
While full trisomy results from meiotic
nondisjunction.
 Mosaic trisomy is due to postzygotic mitotic
nondisjunction.
 Translocation trisomy gives rise to partial
trisomy 18 syndrome.
 The smallest extra region necessary for
expression of serious anomalies of trisomy 18
appears to be 18q11-q12.

Phenotype




The clinical is variable depending on the
level of mosaicism and the tissue involved.
Trisomy 18 severely affects all organ systems
In translocations that result in partial
trisomy or in cases of mosaic trisomy 18.
Clinical expression is less severe and longer
survival is usual.
Edwards Syndrome (47,+18)
Phenotype
 Short
sternum.
 Narrow pelvis.
 Limited hip abduction Hypoplastic nails.
 Dorsiflexed great toes.
 Short neck with excessive skin folds.
An infant with Edwards syndrome
Characteristic hand posture
(Clenched hands)
The index finger overriding the middle finger.
The fifth finger overriding the fourth finger).
Rocker-bottom foot with
prominent calcaneus
The hands of a fetus with Edwards syndrome
Note typically manifests overlapping digits with the second
and fifth fingers overriding the third and fourth fingers
respectively. Overall posturing of the wrists and fingers
suggests contractures.
Diagnosis
Conventional cytogenetic studies
 Full trisomy 18 (95% of cases).
 Trisomy 18 mosaicism (5% of cases)
 Translocation (very rare).
Prenatal diagnosis
Percutaneous umbilical blood sampling (PUBS)
Percutaneous umbilical blood sampling
(PUBS) is of limited use, except in cases
detected late in pregnancy. The
preimplantation diagnosis is not of
any realistic relevance for current care
Chorionic villus sampling (CVS)
Is performed at 10-13 weeks’
gestation. The accuracy (96-98%)
is less than that of mid trimester
amniocentesis because of confined
placental mosaicism and maternal
cell contamination.
Congenital anomalies detectable by
prenatal ultrasonography










Renal defects
Omphalocele
Cardiac defects
Neural tube defects
Choroid plexus cysts
2-vessel umbilical cord
Abnormally shaped fetal head
Intrauterine growth retardation
Abnormal position of fetal fingers
Oligohydramnios/polyhydramnios
Cystic hygroma or lymphangiectasia
9%.
20%
37%
9%
43%
40%
43%
29%
89%
12%.
14%
Genetic counseling
 Recurrence
risk is 1% for full trisomy 18.
 If a parent is a balanced carrier of a
structural rearrangement, the risk is
substantially high.
 Risk should be assessed based on the type
of structural rearrangement.
Consultations
 Clinical
geneticist.
 Developmental pediatrician.
 Cardiologist.
 Ophthalmologist.
 Orthopedist.
 Psychologist.
 Speech language pathologist.
 Audiologist.
 Early childhood educational programs.
Medical/Legal Pitfalls
Failure to identify characteristic symptoms and
signs of Edwards syndrome and refer to a
geneticist for evaluation and genetic counseling
 Failure to request chromosome analysis with
clinical diagnosis of Edwards syndrome
 Failure to offer prenatal screening for pregnant
women
 Failure to offer prenatal diagnosis after birth
of an affected child





Delayed psychomotor development.
Mental retardation (100%).
Neonatal hypotonia followed byhypertonia.
Malformations
Microcephaly. Cerebellar hypoplasia.
Meningoencephalocele. Hydrocephaly.
Holoprosencephaly. Frontal lobe defect.
Migration defect. Arachnoid cyst.
myelomeningocele.
Cranial





Microcephaly.
Elongated skull.
Narrow bifrontal diameter.
Wide fontanels.
Prominent occiput.
Cardiac malformations in 90% of infants.









Ventricular septal defects.
Pulmonary and aortic valve defects.
Atrial septal defects.
Patent ductus arteriosus.
Overriding aorta.
Coarctation of aorta.
Hypoplastic left heart syndrome.
Tetralogy of Fallot.
Transposition of great arteries.
Endocrine
 Thymic
hypoplasia.
 Thyroid hypoplasia.
 Adrenal hypoplasia.
Gastrointestinal
Malrotation of the intestine.
 Ileal atresia and Meckel diverticulum.
 Esophageal atresia with or without
tracheoesophageal fistula and omphalocele.
 Diaphragmatic eventration.
 Prune belly anomaly and absent appendix.
 Diastasis recti and absent gallbladder.
 Accessory spleens and pilonidal sinus.
 Exstrophy of Cloaca and pyloric stenosis.
 Imperforate or malpositioned anus.
 Umbilical, inguinal, and diaphragmatic hernias.

Urinary System
 Bifid uterus.
 Hydroureters.
 Double ureters.
 Megaloureters.
 Hydronephrosis.
 Horseshoe kidneys.
 Unilateral renal agenesis.
 Micromulticystic kidneys.
 Hypospadias.
 Bifid uterus.
 Cryptorchidism.
 Micropenis in males.
 Hypoplastic ovaries.
 Hypoplasia of labia and ovaries.
 Clitoral hypertrophy in females.
Surgical Care
Because of the extremely poor prognosis,
surgical repair of severe congenital
anomalies such as esophageal atresia or
congenital heart defects is not likely to
improve the survival rate of infants
and should be discussed with families.
Prognosis
Survival rates
 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.