Congenital Abnormalities And Their Scientific Basic Flashcards
Meaning of congenital
Present at birth, does not denote aetiology
What is an anomaly
Structural deviation from the norm
What are congenital abnormalities
Occur when normal embryonic development is disrupted
What is a deformation
Late changes in previously normal structures (mechanical effect)
What is disruption
Secondary disturbance due to early influence of external factors
What is malformation
Primary disturbance of embryogenesis
How are congenital anomalies classified
By cause
Timing ( explains problem)
Difference between disruption and deformation
Disruption: starts out okay then goes wrong
Deformation = was okay but then is squashed
What is sequence:
One primary error with a cascade of events and consequences
What can aetiology be grouped into
Single gene defects = 20%
Chromosomal = 10%
Polygenic = 25-30%
Teratogenic = 6-9%
Unknown = 35-40%
What is the difference between a primary and secondary anomaly
Primary is at the genetic level and maybe due to chromosomal, single gene or polygenic factors
Whilst a secondary anomaly is due to an external factor such as a teratogen
Examples of congenital infections that are teratogenous
Toxoplasmosis
Others = varicella, parvovirus and syphilis
Rubella
Cytomegalovirus
HIV
Examples of environmental pollutants and drugs that are teratogenic
Vitamin A
Pesticides
Medication
Alcohol
Examples of maternal metabolic diseases that maybe teratogenic
DM
What else is teratogenic
Radiation exposure
What are the early effects (classification by timing)
In 2-4 weeks
Polytropic defects = scattered pattern with significant effect on cell populations
What are the late effects
4-8 weeks of gestation
Monotropic effects - localised defects due to formation of sub-populations of cells
Effects in the foetal period -
Greater than 9 weeks
Organogenesis so specific organs or systems are affected
Examples of deformities
Talipes - club foot
Congenital hip deformation
What is talipes
Example of a deformity in which the feet have been squashed during development and have a clubbed appearance
What is congenital hip deformation
Where morphology and alignment of the hip/hips have been squashed during development
Examples of disruption
Amniotic bands (strips of amniotic membrane)
Poland anomaly
What are amniotic bands
Form of disruptive anomaly in which strips of the amniotic membrane wrap around limbs or digits and cause constriction of the blood supply. Can cause ischaemia and loss of digit or limb
What is the Poland anomaly
A form of disruptive anomaly in which there is unilateral absence of pectoralis major muscle due to the interruption of the subclavian artery. Loss of supply and nutrients occurs
Examples of sequence anomalies
Potter sequence
Pierre robin sequence
What is potter sequence
True kidneys do not develop properly (renal agenesis) so no foetal urine production which causes oligohydroamnios
The lack of amniotic fluid causes mechanical squashing
Results in baby with limb deformities, respiratory failure due to pulmonary hypoplasia.
Face has low set ears, slanted eyes and a beaked nose
What is Pierre robin sequence
Begins with mandibular hyperplasia which does not allow tongue to drop which then affects the development of the palate
In what ways can a single gene be impacted
Mutation
Deletion
In which ways can chromosomes be impacted
Translocation
Microdeletions
Duplications as seen in downs, Edward’s and Pataus
What is di George syndrome
Deletion of a section of the 22nd chromosome
Specifically 22q11.2
Contains an important gene for development called TBX-1
What gene is implicated in di George syndrome
TBX-1
What are the range of anomalies experienced in di George syndrome
Hormonal and immunological disturbances due to development of thymus and parathyroid glands being affected
Speech delay and delayed development in infancy
Cardiac anomalies
Hypocalcemia?
The embryonic development of which structures is affected in Di George syndrome
Failure to develop 3 and 4th pharyngeal pouches which gives rise to thymus and parathyroid glands
What is charge syndrome
A heterozygous mutation in CHD7 gene
CHD7 = chromodomain helicase DNA binding domain, ATP dependent chromatin remodeller
Why is expression of CHD7 gene vital
Expression allows for the production of multi potent neural crest cells
So is important in the development of the heart, the head + neck and the adrenal medulla
What does CHARGE stand for
C = coloboma = missing piece of tissue that makes up your eye
H = heart defects
A = choanol atresia (choanae are blocked by bone or tissue)
R = growth and developmental retardation
G = genital hypoplasia
E = ear defects
What do the neural crest cells give rise to
Sensory ganglia of the cranial nerves
Ganglia of the ANS
Spinal ganglia
Glial cells
Schwann cells
Pigment cells - melanocytes
Adrenomedullary cells
Calcitonin producing cells
Spina bifida is resulted when failure to close which Neuropore occurs
Caudal neuropore
Spina bifida defect can occur anywhere along the length of the neural tube but where is the most common location
Lumbosacral region
What also accompanies spina bifida
Hydrocephalus
And sometimes neurological deficits
How is development of spina bifida multi-factorial
Genetic
Environmental
Maternal nutritional status
What is the incidence of Di George syndrome
1 in every 3000 births
Incidence of FAS
1/100 births
The facial skeleton is derived from what
Neural crest cells populating the pharyngeal arches
The migration of neural crest cells is extremely sensitive to alcohol
What is congenital rubella syndrome
Viral infections affects development of organs of special senses, heart
Microcephaly
PDA patent ductus arteriosus
Cataracts
Congenital anomalies affect what % of liveborn infants
3%
Causing perinatal and neonatal death and disability
What is the lifelong impact to child and family y
20-30% admissions to tertiary care.
Emotional and physical wellbeing impacted
Financial cost
Historical beliefs still present in some cultures where it is believed that cause is supernatural/ associated with witchcraft
What is the number one cause of neonatal deaths worldwide
Pre term birth complications 34%
Congenital anomalies account for 9%
What types of screening are available
Pre conception = genetic counselling
Antenatal screening = in first and second trimester
Newborn screening examination
What antenatal screening is available in first trimester
Triple test (looks at levels of alpha fetoprotein, hCG and estriol
Nucal fold (increased thickness is associated with anomalies)
What antenatal screening cna be carried out in the second trimester
Anomaly scan at 20 weeks
