Detecting congenital abnormalities Flashcards
State the definition of a congenital anomaly and teratology
CONGENITAL ANOMALY- abnormality of structure, function or disorder of metabolism that is present at birth and results in a physical or mental disability
TERATOLOGY- study of causes and biological processes leading to abnormal development at fundamental and clinical level, and appropriate measures for prevention
What is the worldwide impact of congenital abnormalities?
Neonatal mortality
- Preterm birth
- Birth asphyxia and trauma
- Neonatal sepsis
Long term disability
2% in UK
What are the most common severe congenital anomalies?
What are the causes of congenital anomalies?
- Heart defects, neural tube defects, Downs Syndrome
- 50% iatrogenic
- genetic (inherited vs sporadic mutation)
- infection (rubella, syphilis, zika)
- socioeconomical/demographic factors e.g. nutrition, environment, age
How can congenital anomalies can be prevented?
- Vaccination (Rubella)
- Adequate intake of folic acid, iodine through supplementation or fortification of food
- Appropriate antenatal care
How do genetics contribute to congenital anomalies
- inherited genetic anomaly
- mutations during development
- some ethnic communities have a higher prevalence of rare genetic mutations e.g. CF and Haemophilia C
- Consaguinity increases prevalence of
Discuss screening of chromosomal abnormalities
- high risk patients (recurrent pregnancy loss, FHx)
- In all patients through UK AN screening programme
How are structural abnormalities classified?
- Malformation (of organ e.g. transposition of the great arteries)
- Disruption- alteration of an already formed organ (e.g. bowel atresia)
- Deformation; caused by extrinsic pressures (e.g. mechanical)
- Dysplasia: abnormal organisation of cells/tissues
State the different between a syndrome and a sequence
SYNDROME
- multiple congenital abnormalities
- group of abnormalities due to single aetiology
- e.g. single chromosomal/gene problem
SEQUENCE
- multiple congenital abnormalities as a result of ONE abnormality
- Potters sequence: renal agenesis leading to oligohydraminios leading to skeletal deformities
For each of the following syndromes, state the chromosomal anomaly
- DOWNS
- EDWARDS
- PATAUS
- TURNERS
- KLINEFELTERS
- Downs: Trisomy 21
- Edwards: Trisomy 18
- Pataus: Trisomy 13
- Turners: XO
- Klinefelters: XXY
Describe the facial features of Down’s syndrome
Any other features?
FACIAL
- small nose and flat nasal bridge
- large tongue (may stick out)
- eyes that slant upwards and outwards
- a flat back of the head
OTHER
- broad hands with short fingers
- single palmar crease
- below average Wt & Lt at birth
- cardiac defects
- duodenal atresia
- learning disability
State a facial, skeletal, GI, urogenital and neurological abnormality associated with Edwards Syndrome
FACIAL
- small, abnormally shaped head
- small jaw and mouth
- lowset ears
- cleft lip/palate
SKELETAL
- long overlapping fingers, underdeveloped thumbs, clenched fists
GI
- omphalocele
- oesophageal atresia and/or tracheo-oesophageal fistula
- umbilical/inguinal hernia
- pyloric stenosis
NEUROLOGICAL
- anencephaly, hydrocephaly, brain malformations, severe learnign disability, seizures
- Congenital heart defects, pulmonary hypoplasia
- Die in year 1
State a facial, GI, CNS and skeletal abnormality associated with Pataus syndrome
FACIAL
- cleft lip/palate
- abnormally small eyes or absence of 1 r both eyes
- reduced distance between eyes
- exomphalos
GI
- omphalocele, exomphalos
CNS
- holoprosencephaly (single brain)
SKELETAL
- polydactyly
- rounded bottom of feet (“rocker-bottom” feet)
Congenital heart defects
Small penis in boys, large clitoris in girls
Die within days of birth
What is a teratogen?
An agent, such a virus, a drug or radiation that causes malformation of an embryo or fetus
Warfarin and thalidomide are both teratogens.
Give the type and effect of each
DRUGS
Warfarin –> chondrodysplasia, microcephaly
Thalidomide –> limb defects/heart defects
Give an example of a viral teratogen
Effects?
Syphilis, rubella
Rubella -> deafness
Pesticides, radiation and alcohol are chemical teratogens.
State their individual effects
Pesticide –> neural tube defects
Radiation –> microcephaly, spina bifida
Alcohol –> FAS (maxillary hypoplasia, mental retardation)
How can androgens be teratogenic?
Cause masculinisation of external genitalia
Which periods are particularly susceptible to teratogenesis?
Weeks 3-8
- declines after this
How do children with fetal alcohol syndrome (FAS) present?
Diagnosed late in children due to under performance at school
- Epicanthal folds
- Flat nasal bridge
- Small palpebral fissures
- “Railroad track” ears
- Upturned nose
- Smooth philtrium
- Thin upper lip
Outline the thalidomide story
1950s drug used to treat morning sickness
- Withdrawn in 1961 after increased deformed babies
In 2008 approved for treatment of multiple myeloma
When are congenital abnormalities detected?
61% antenatally
8% at birth
6% at 2-4 weeks
18% after first month
Some not until adult life
How can we detect/prevent congenital abnormalities?
Pre-implantation genetic testing in IVF
Diagnostic in utero tests - amniocentesis, CVS
AN Screening program
Ultrasound scans at 11 and 20 weeks, third trimester
Why should we detect congenital abnormalities?
Termination?
Treatment:
- in utero: cleft palate/pulmonary shunts/tumours, transfusions
- maternal antibiotics
- post delivery: diabetes
- preparation for parents e.g. support groups
Commonest congenital abnormality?
Limb defects Spina bifida Heart defects Chromosomal abnormalities Anencephaly
Chromosomal abnormalities
