Congenital Defects

What does "congenital" mean?

Present at birth, does not have to be genetic. Examples are HIV or cleft lip.

What is the leading cause of neonatal death worldwide?

Preterm birth related problems.

What is the difference between a single primary defect and multiple malformation syndrome?

- A single primary defect involves a SINGLE a structure being defected, rest of the child is normal. - i.e. cleft lip. - Multiple malformation syndrome is 1+ anomalies of 2 or more systems. - i.e. cleft palate with CVD.

Give some examples of common single primary defects.

- Cleft lip. - Talipes. - Neural tube defects. - Ventricular septal defect.

Define "genotype" and "phenotype".

- Genotype: Genetic constitution of individual. - Phenotype: Observable manifestation of the genotype.

If a defect occurs during organogenesis, what structures could be affected?

- Limb: Amputation. - GU system: Exstrophy of bladder. - CNS: Spina bifida. - Face: Cleft lip. - Gut: Duodenal atresia. - Heart: Ventricular septal defect.

What are some preventative methods for congenital defect?

- Oral folate supplement. - Rubella immunisation. - Optimal maternal health. - Antenatal screening. - Newborn screening examination

Rank these from earliest to latest: neonatal, perinatal, post-neonatal.

- Perinatal. - Neonatal. - Post-neonatal

Give an example of a structural defect and a functional defect.

- Structural: Cleft palate. - Functional: PKU. Phenylketonuria, impaired metabolism of amino acid phenylalanine.

What 3 things must a teratogen do to cause abnormality?

1) Be present at the right time. 2) Be present in the right dose. 3) Affect a genetically susceptible individual.

What are the 2 phases that congenital defects can occur in? When does organogenesis occur?

1) Embryonic phase (from 0-8 weeks). 2) Foetal phase (9-parturition). - Weeks 2-8.

What are the 4 errors that can cause a single primary defect?

1) Malformation. 2) Disruption. 3) Deformation. 4) Sequence. ******* Doesn't Shoot

What 4 things are thought to cause congenital defects?

1) Unknown! 65-70%. Sporadic and random. 2) Single gene or chromosomal mutation. Inherited or new. 3) Environmental. Teratogens/illness/micronutrient deficiency. 4) Multifactorial. Genes + environment + random chance.

What is foetal alcohol syndrome?

A congenital defect caused by teratogenic effects of alcohol. - Learning difficulties, dysmorphic features, IUGR, behaviour problems, underweight. - Alcohol crosses the placental barrier and stunts foetal growth.

What is oligohydramnios? What can it cause?

A deficiency of amniotic fluid, the opposite of polyhydramnios. - Talipes/Congenital hip dislocation due to growth restriction.

What is a disruption? Give an example.

A destructive process which alters normal structures after their formation. - Amniotic bands cutting off limbs. - Cardiovascular accidents.

What is a sequence? What can it cause?

A pattern of multiple anomalies when a SPD occurs early, influencing subsequent development. - Pierre Robin sequence where the jaw is too small, cleft palate, airway obstruction.

What is a syndrome? Give an example.

A recognised pattern of anomalies with a single specific cause. - Multiple malformation syndrome is 2+ systems being abnormal with a common aetiology. - Down's syndrome.

What is a cleft lip?

A single primary defect in which there is a fissure on the upper lip going towards the nose.

What is Pierre robin sequence?

A single primary defect that causes the jaw to be too small, tongue to be posteriorly displaced, cleft palate and airway obstruction.

What is an "anomaly"?

A structural deviation from the norm. Example is a cleft lip.

What is the difference between a sequence and a syndrome?

A syndrome is a condition with multiple factors related to the same genetic condition e.g. Trisomy 21. - A sequence is a pattern of problems believed to have occurred from a single event. E.g. Pierre robin.

What is Poland anomaly? What error type is it?

Absence/severe underdevelopment of the pectoralis muscle, disruption.

What is a teratogen? Give 3 classes.

Any agent that can disturb the development of the foetus or embryo. 1) Infectious. Rubella, CMV (cytomegalovirus), herpes, toxoplasmosis. 2) Chemical. Smoking/cocaine/alcohol. 3) Physical. Ionising radiation, hyperthermia.

What is a congenital defect?

Any structural or functional defect that began before birth or the cause of which was present before birth. Can be identified at any age.

What is a malformation? Give an example.

Arises during initial formation of the embryo as a result of genetic and environmental factors during organogenesis. - VSD, cleft lip.

Give an example of a single gene defect that can lead to a syndrome.

CREBBP gene mutation in Rubenstein Taybi Syndrome.

What is talipes? Congenital talipes equinovarus (CTEV).

Club foot. Feet bend inwards towards the midline.

What is the leading cause of perinatal death and post neonatal death in the UK?

Congenital defect. - Also a major cause of death in general in developing countries.

What is a risk factor for single gene/chromosomal mutation?

Consanguinity, cousins reproducing.

What is post neonatal mortality?

Death of a child aged 29 days to 1 year.

What is perinatal mortality?

Death of a foetus/baby from 22 weeks gestation up to 7 days after birth. - Late foetal death to 1 week postpartum.

What is neonatal mortality?

Death of a live born baby within first 28 days of life. - More common in developing countries due to lack of access to meds.

What is the most common condition caused by a teratogen?

Foetal alcohol syndrome.

How can maternal diabetes be teratogenic?

High levels of glucose in the mother can significantly increase anomaly rate: Heart defects, CNS abnormalities. - Lower risk if glucose is well controlled, undiagnosed is risky.

Which congenital defect type occurs during structure formation?

Malformation, during organogenesis 2-8 weeks.

What is a deformation? Give an example.

Moulding of a normally differentiated body part by mechanical forces ( - Talipes. Congenital hip dislocation.

What is parturition? What does postpartum mean?

Parturition is childbirth. - Post childbirth.

How are multiple malformation syndromes caused?

Single gene/chromosomal defects and teratogen exposure.

Give one example of a famous teratogen that caused limb amputation.

Thalidomide. Caused thalidomide phocomelia.

Give an example of a chromosomal defect that can lead to a syndrome.

Trisomy 21.

What is congenital rubella syndrome? What class of teratogen causes it?

When a mother contacts rubella when pregnant, baby is born with rubella. - An infectious teratogen (rubella).