24. Congenital abnormalities and teratology

Question 1

Congenital anomaly

Answer 1

abnormality of structure, function or disorder of metabolism that is present at birth and results in a physical or mental disability
Alternate terms: birth defects, clinical dysmorphologies, congenital anomaly, congenital malformation

Question 2

Teratology

Answer 2

study of causes and biological processes leading to abnormal development at fundamental and clinical level, and appropriate measures for prevention

Question 3

Incidence

Answer 3

number of new cases in a given population over a specific time period
But not able to identify ALLnew cases (miscarriage etc) and unable to measure all pregnancies so use prevalence used instead.

Question 4

Birth prevalence

Answer 4

Birth prevalence means (fetal loss, stillbirth, TOPs and births) per 10,000 births

Question 5

Worldwide impact of congenital abnormalities

Answer 5

An estimated 303 000 newborns die within 4 weeks of birth every year, worldwide, due to congenital anomalies.
Congenital anomalies can contribute to long-term disability – causing significant impacts on individuals, families, health-care systems, and societies.

Question 6

Causes of congenital anomalies

Answer 6

The most common, severe congenital anomalies are heart defects, neural tube defects and Down syndrome
About 50% = no known cause, but may be the result of one or more of the following risk factors
Genetic – inherited vs sporadic mutation. NB consanguinuity
Infectious – Rubella, Syphilis, Zika
Teratogens
Socio-economic / demographics - nutritional (eg folatic acid) or environmental factors, age

Some congenital anomalies can be prevented

Vaccination (Rubella)
Adequate intake of folic acid or iodine through fortification of staple foods or supplementation
Appropriate Antenatal care.

Question 7

Most common congenital anomaly

Answer 7

Congenital heart defects and chromosomal

Question 8

Genetic/congenital abnormalities

Answer 8

Genes play an important role in many congenital anomalies.

• Inherited genetic anomaly
• Mutations during development

Consanguinity increases the prevalence of rare genetic congenital anomalies and nearly doubles the risk for neonatal and childhood death, intellectual disability and other anomalies.

Some ethnic communities (such as Ashkenazi Jews or Finns) have a comparatively high prevalence of rare genetic mutations such as Cystic Fibrosis and Haemophilia C.

Screening for genetic disorders can be undertaken
in high risk patients – eg. those with previous recurrent pregnancy loss, or family history for a particular problem

In ALL patients – through the UK AN Screening Programme

Question 9

Classification of structural abnormalities

Answer 9

Malformation: flawed development of a structure or organ (eg. transposition of the great arteries)

Disruption: alteration of an already formed organ (vascular event eg bowel atresia)

Deformation: alteration in structure caused by extrinsic pressures (mechanical eg talipes due to reduced liquor)

Dysplasia: abnormal organisation of cells
or tissues

Question 10

Syndrome

Answer 10

Multiple congenital abnormalities
Group of abnormalities due a single aetiology
eg single chromosomal/gene problem

Question 11

Sequence

Answer 11

Multiple congenital abnormalities but as a consequence of one abnormality

Question 12

Potters sequence

Answer 12

Potters sequence:
renal agenesis leading to
oligohydramnios
leading to skeletal deformities

Question 13

Down’s syndrome facial features

Answer 13

Facial Features
small nose and flat nasal bridge/ flat face
large tongue that may stick outof mouth
eyes that slant upwards and outwards
a flat back of the head / thickened skin

Question 14

Non-facial external features of Down’s syndrome

Answer 14

Other external features:
broad hands with short fingers
single palmar crease
below-average weight and length at birth

Question 15

Other problems (non-external) of Down’s syndrome

Answer 15

Other problems:

Cardiac defects, duodenal atresia, mild to moderate learning disability

Question 16

Edward’s syndrome T18

Answer 16

Facial abnormalities: small, abnormally shaped head, small jaw and mouth, low-set ears, cleft lip/palate

Skeletal abnormalities: long fingers that overlap, with underdeveloped thumbs and clenched fists,

Congenital heart defects: >90%
Gastrointestinal abnormalities: omphalocele, oesophageal atresia ± tracheo-oesophageal fistula, umbilical or inguinal hernia, pyloric stenosis

Urogenital abnormalities: Gonadal dysgenesis, horseshoe kidney, hydronephrosis, cystic kidneys, renal agenesis.

Neurological problems: anencephaly, hydrocephaly and other brain malformations, severe learning disability, seizures.

Pulmonary hypoplasia

Usually die within first year of life

Question 17

Patau’s syndrome T13

Answer 17

Congenital heart defects: >80%

Facial abnormalities: cleft lip / palate abnormally small eye or eyes (microphthalmia) or absence of 1 or both eyes (anophthalmia), reduced distance between the eyes (hypotelorism), microcephaly

Gastrointestinal abnormalities: eg, omphalocele, exomphalos
CNS disorder- holoprosencephaly – single brain

Abnormally small penis in boys,enlarged clitoris in girls

Skeletal: as extra fingers or toes (polydactyly),and a rounded bottom to the feet, known as ‘rocker-bottom’ feet

Usually die within days of birth

Question 18

What is a teratogen?

Answer 18

Teratogen: an agent, such as a virus, a drug, or radiation, that causes malformation of an embryo or fetus.

Question 19

Zika virus

Answer 19

Uncertain implications, International guidance on avoidance of travelling to areas ‘at risk’, protocols for testing exposed patients, treatment guidance and scan monitoring

Question 20

Warfarin effect on pregnancy

Answer 20

chondrodysplasia, microcephaly

Question 21

Thalidomide effect on pregnancy

Answer 21

limb defects/heart defects

Question 22

Rubella effect on pregnancy

Answer 22

rubella (deafness)

Question 23

pesticide effect on pregnancy

Answer 23

neural tube defects

Question 24

radiation effect on pregnancy

Answer 24

microcephaly, spina bifida

Question 25

alcohol effect on pregnancy

Answer 25

foetal alcohol syndrome (FAS, maxillary hypoplasia, mental retardation)

Question 26

Androgens effect on pregnancy

Answer 26

masculinisation of external genitalia

Question 27

Foetal alcohol syndrome

Answer 27

Results from chronic alcohol exposure. Often diagnosed late in children - under performance at school. Lower intellect and learning disabilities.

Question 28

Detecting congenital abnormalities

Answer 28

61% detected antenatally – eg. at screening or at anomaly scan
8% at birth – eg. due to external features or due to immediate deterioration in condition at birth
6% 2-4 weeks
18% after first month
(some not until adult life)

Question 29

Detecting/preventing congenital abnormalities

Answer 29

Pre-implantation genetic testing - IVF
AN Screening Program
Diagnostic in Utero tests 
– amniocentesis, CVS
Ultrasound scans

Question 30

Ultrasound scans

Answer 30

11+weeks
Anencephaly, Major Limb defects
Combined screening : Nuchal translucency combined with maternal biochemistry

20 weeks (anomaly)
Heart (4 chamber view), Brain / spine, Skeletal, Cleft lip and palate, Bowel, kidneys, Movements

Third trimester
Growth, organs as per 20/40, liquor volume, movements

Question 31

Why detect?

Answer 31

Termination
Treatment:
In utero: cleft palate/ pulmonary shunts /tumours, transfusions, balloon occlusion of diaphragmatic hernia
Maternal: Antibiotics (eg for toxoplasmosis)
Post-delivery: CHD deliver in tertiary centre for immediate surgery
Time Delivery: diabetes
Preparation for parents – eg. Downs group / support