2 cases of congenital abnormality Lent term year 1.
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Transcript of 2 cases of congenital abnormality Lent term year 1.
2 cases of congenital abnormality
Lent term year 1
Case 1• A 27 year old woman becomes pregnant
and undergoes a triple test at 14 weeks gestation
• The results showed:
AFP 56.7 kU/l 0.6 MoM
hCG 32.2 IU/ml 3.97 MoM
uE3 2.9 nmol/L 0.56 MoM
• i.e. Risk for Down syndrome 1:100
The analytes:
• AFP: alphafetoprotein. Produced by yolk sac and fetal liver. Excreted into amniotic fluid via fetal urine. Crosses placenta into maternal circulation
• hCG: human chorionic gonadotrophin. Glycoprotein produced by trophoblast. Beta sub-unit specific for pregnancy
• UE3: unconjugated oestriol. Synthesised in placenta
Then….
• She undergoes amniocentesis, which confirms the baby has Down syndrome
Down syndrome
• Features of Down syndrome
• Screening: triple test/ultrasound
• Diagnosis: chromosome tests
• Outcome
What is Down syndrome?• Clinical syndrome described by John
Langdon Down in 1866
• Trisomy 21 in 90% cases identified by Prof Lejeune in 1959
Clinical features• Epicanthic folds
• Single palmar crease
• Flat occiput
• Macroglossia
• Cardiac murmur (1:3 congenital heart disease)
• Poor muscle tone/feeding/weight gain
• Developmental and learning delay
Assessing the risk for Down syndrome pregnancy
• Maternal age
• “Triple test”
• ultrasound
Maternal age at term
• <25 1:1500
• 27 1:1200
• 30 1:910
• 35 1:380
• 40 1:110
• 45 1:30
The “triple test”• Introduced to improve sensitivity and
specificity of testing
• Uses 3 analytes: AFP(alphafetoprotein), hCG (human chorionic gonadotrophin) and uE3 (uncongugated Oestriol)
• Combines with maternal age to give risk
In Down syndrome:
• AFP lower – on average 0.7 MoM
• hCG higher
• uE3 lower
• Offered as part of NHS Antenatal and Newborn Screening Programme
• http://www.screening.nhs.uk/downs/home.htm
Ultrasound: Nuchal translucency
Assessing risk
• Offer amniocentesis if risk >1:250
• May combine triple and nuchal screening test to improve sensitivity and specificity of risk
Amniocentesis
Chromosome tests
• Culture and staining
• PCR (polymerase chain reaction)
• FISH (Fluorescent in situ hybridisation)
Normal PCR
FISH (offered if risk>1:30)
outcome• In practice most parents opt for
termination of pregnancy• Individuals vary greatly in level of disability• High incidence of congenital heart
disease, duodenal atresia• Some children attend mainstream school
with help• Increased incidence of leukaemia and
Alzheimer’s disease in later life
Case 2• A 27 year old undergoes a triple test at 14
weeks gestation in her first pregnency
• The results showed:
AFP 126.7 kU/l 3.20 MoM
hCG 32.2 IU/ml 0.97 MoM
uE3 2.9 nmol/L 1.16 MoM
• She goes on to have an ultrasound at 16 weeks
What can cause a raised AFP?
Causes of a raised AFP (>2.0 MoM)
• Lab error/wrong gestational age• Multiple pregnancy• Hydatidiform mole (trophoblastic tumour)• Intrauterine death• Anencephaly• Other open neural tube defects: spina
bifida• Omphalocele/gastroschisis
“snowstorm effect”
Neural tube defects• Due to incomplete development of neural
tube from ectoderm• May present at different sites and different
grades of severity• Often associated with hydrocephalus• Not usually linked with chromosome
abnormality• Evidence that folic acid supplemants
reduce the incidence
In this case• The patient was referred for ultrasound
which showed a meningocele in the lumbar spine
What is the likely outcome in this pregnancy?
• Natural history difficult to predict from ultrasound
• Anencephaly incompatible with life after birth
• 50% babies with open SB survive after 5y
• Majority of survivors have major degree of disability: lower limb/bladder paralysis/hydrocephalus/learning disability
How would you manage these pregnancies?
• The majority of patients request termination
• In England, Scotland and Wales legal to 24 weeks under Abortion Act
• 2 doctors required to sign for clause E, which states: “there is a substantial risk that if a child were born it would suffer from such physical or mental abnormalities as to be seriously handicapped”