24. Congenital abnormalities and teratology Flashcards
Congenital anomaly
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
Teratology
study of causes and biological processes leading to abnormal development at fundamental and clinical level, and appropriate measures for prevention
Incidence
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.
Birth prevalence
Birth prevalence means (fetal loss, stillbirth, TOPs and births) per 10,000 births
Worldwide impact of congenital abnormalities
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.
Causes of congenital anomalies
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.
Most common congenital anomaly
Congenital heart defects and chromosomal
Genetic/congenital abnormalities
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
Classification of structural abnormalities
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
Syndrome
Multiple congenital abnormalities
Group of abnormalities due a single aetiology
eg single chromosomal/gene problem
Sequence
Multiple congenital abnormalities but as a consequence of one abnormality
Potters sequence
Potters sequence:
renal agenesis leading to
oligohydramnios
leading to skeletal deformities
Down’s syndrome facial features
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
Non-facial external features of Down’s syndrome
Other external features:
broad hands with short fingers
single palmar crease
below-average weight and length at birth
Other problems (non-external) of Down’s syndrome
Other problems:
Cardiac defects, duodenal atresia, mild to moderate learning disability
Edward’s syndrome T18
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
Patau’s syndrome T13
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
What is a teratogen?
Teratogen: an agent, such as a virus, a drug, or radiation, that causes malformation of an embryo or fetus.
Zika virus
Uncertain implications, International guidance on avoidance of travelling to areas ‘at risk’, protocols for testing exposed patients, treatment guidance and scan monitoring
Warfarin effect on pregnancy
chondrodysplasia, microcephaly
Thalidomide effect on pregnancy
limb defects/heart defects
Rubella effect on pregnancy
rubella (deafness)
pesticide effect on pregnancy
neural tube defects
radiation effect on pregnancy
microcephaly, spina bifida
alcohol effect on pregnancy
foetal alcohol syndrome (FAS, maxillary hypoplasia, mental retardation)
Androgens effect on pregnancy
masculinisation of external genitalia
Foetal alcohol syndrome
Results from chronic alcohol exposure. Often diagnosed late in children - under performance at school. Lower intellect and learning disabilities.
Detecting congenital abnormalities
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)
Detecting/preventing congenital abnormalities
Pre-implantation genetic testing - IVF AN Screening Program Diagnostic in Utero tests – amniocentesis, CVS Ultrasound scans
Ultrasound scans
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
Why detect?
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
