Congenital Abnormalities Flashcards
Morphogenesis
Organ and tissue development in the fetus.
Malformations:
-Definition
- Intrinsic error of fetal development –> morphological defect of an organ / part of an organ / larger region of the body.
- Primary errors.
- Result of single gene / chromosomal defect OR multifactorial (more common).
- Can involve single body systems or multiple.
Malformations:
-Examples
- Polydactyly (one or more extra digits).
- Syndactyly (fusion of digits).
- Cleft lip +/- cleft palate.
- Complex congenital heart disease.
- Large abdominal wall defects.
- Neural tube defects.
- Hirschsprungs (absence of nerve cells in colon).
Disruptions:
-Definition
- Extrinsic distrubance in foetal development –> morphological defect of an organ / part of an organ / larger region of body.
- Secondary destruction of organs / body region that was previously normal in development.
- Not heritable.
Disruptions:
-Examples
- Amniotic bands.
- Environmental agents.
Deformations:
-Definition
- Extrinsic disturbance of development.
- An abnormal form, shape or position of part of the body caused by mechanical forces.
- Pathogenesis = localised or generalised compression of growing fetus by abnormal forces.
Deformations:
-Maternal factors contributing to excessive compression
- Uterine constraint.
- First pregnancy.
- Small uterus.
- Malformed (bicornuate) uterus (heart shaped uterus).
- Leiomyomas (uterine fibriods).
Deformations:
-Foetal / placental factors contributing to excessive compression
- Oligohydramnios (decreased amniotic fluid for gestation).
- Multiple foetusus.
- Abnormal foetus presentation.
Deformations:
-Examples
Talipes equiovarus (club feet).
Sequence:
-Definition
- Cascade of anomalies triggered by one initiating defect / issue.
- Can result in malformation, disruption, or deformation.
Sequence:
-Examples
Oligohydramnios sequence (aka Potter sequence) =
Significant oligohydramnios^ –> foetal compression –> talipes equinovarus, flattened facies, positioning defects of hands, breech presentaion, pulmonary hypoplasia +/- hip dislocation +/- amnion nodosum (amnion nodules)
Causes = amniotic leak, renal agenesis, foetal urinary tract obstruction, uteroplacental insufficiency.
Malformation syndrome:
-Definition
- Group of congenital abnormalities that are pathologically related (i.e. not explained by single initiating defect).
Malformation syndrome:
-Examples
Fused / ill-formed mid-face with maldevelopment of brain and cardiac defects.
Agenesis
Complete abscence of an organ and its associated primordium.^
^Primordium = organ, structure, or tissue in earliest stage of development.
Aplasia
Absence of an organ secondary to failure of existing primordium growth.
Atresia
Absence of an opening (usually hollow visceral organs e.g. trachea, intestine, bile duct).
Hypoplasia
Decreased cell numbers –> incomplete development or decreased size of an organ.
Hyperplasia
Increased cell numbers –> overdevelopment or increased size of an organ.
Hypotrophy
Decreased cell size –> organ abnormality.
Hypertrophy
Increased cell size –> organ abnormality.
Dysplasia
Abnormal organisation of cells.
Genetic causes of congenital abnormalities
- Chromosomal syndromes (10 - 15%).
- Mendelian inheritance (2 - 10%).
Genetic causes of congenital abnormalities:
-Example of Mendelian inheritance
Holoprosencephaly (abnormal development of brain) secondary to loss of Hedghog signalling.
Environmental causes of congenital abnormalities
Maternal / placental infections:
- Rubella.
- Toxoplasmosis.
- Syphilis.
- CMV.
- HIV
Maternal disease status:
- Diabetes.
- PKU.
- Endocrinopathies (including severe obesity).
Drugs and chemicals:
- EtOH, smoking.
- Folic acid antagonists.
- Androgens.
- Phenytoin.
- Thalidomide.
- Warfarin.
- 13-cis-retinoic acid.
What does a positive AChE stain indicate and what disease is this seen in
Indicates:
- Indicates loss of ganglion cells (nerve cells in colon).
Seen in:
- Hirschsprungs.
Malformations:
Lymphatic malformation:
-What is it, how can it be identified histologically and why
What it is:
- Intrinsic error of foetal development.
- Abnormal swellings consisting of multiple lymphatic cysts.
- Cysts contains lymphatic vessels which do not connect to normal lymphatic system.
Histology:
- Use D2-40 stain.
Why:
- D2-40 is a monoclonal antibody which reacts to podoplanin.
- Podoplanin is a transmembrane, oncofoetal, glycoprotein found on lymphatic endothelium, mesothelium and foetal testis.
- Staining positive with D2-40 indicates podoplanin, which indicates lymphatic tissue.
What is Foetal Hydrops, and what are some common causes?
What it is:
- Accumulation of fluid during intrauterine growth.
- Fluid distribution can be generalised (hydrops fetalis - lethal), localised (isolated pleural / peritoneal effusions), or nuchal (cystic hygroma).
Causes - immune:
- Haemolytic disease of newborn / Rh incompatibility.
Causes - non-immune:
- Cardiovascular defects.
- Chromosomal abnormalities (e.g. Turners, T21, T18).
- Fetal anaemia (e.g. homozygous alpha thal).
- Tranplacental infections (e.g. Parvovirus).
- Twin-twin transfusion syndrome in monozygous twins.
Which region of the intestine is usually involved in necrotising enterocolitis
Ileocaecal region (vascular “watershed”)
