Congenital Abnormalities

Question 1

Morphogenesis

Answer 1

Organ and tissue development in the fetus.

Question 2

Malformations:
-Definition

Answer 2

• 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.

Question 3

Malformations:
-Examples

Answer 3

• 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).

Question 4

Disruptions:
-Definition

Answer 4

• 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.

Question 5

Disruptions:
-Examples

Answer 5

• Amniotic bands.
• Environmental agents.

Question 6

Deformations:
-Definition

Answer 6

• 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.

Question 7

Deformations:
-Maternal factors contributing to excessive compression

Answer 7

• Uterine constraint.
• First pregnancy.
• Small uterus.
• Malformed (bicornuate) uterus (heart shaped uterus).
• Leiomyomas (uterine fibriods).

Question 8

Deformations:
-Foetal / placental factors contributing to excessive compression

Answer 8

• Oligohydramnios (decreased amniotic fluid for gestation).
• Multiple foetusus.
• Abnormal foetus presentation.

Question 9

Deformations:
-Examples

Answer 9

Talipes equiovarus (club feet).

Question 10

Sequence:
-Definition

Answer 10

• Cascade of anomalies triggered by one initiating defect / issue.
• Can result in malformation, disruption, or deformation.

Question 11

Sequence:
-Examples

Answer 11

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.

Question 12

Malformation syndrome:
-Definition

Answer 12

• Group of congenital abnormalities that are pathologically related (i.e. not explained by single initiating defect).

Question 13

Malformation syndrome:
-Examples

Answer 13

Fused / ill-formed mid-face with maldevelopment of brain and cardiac defects.

Question 14

Agenesis

Answer 14

Complete abscence of an organ and its associated primordium.^

^Primordium = organ, structure, or tissue in earliest stage of development.

Question 15

Aplasia

Answer 15

Absence of an organ secondary to failure of existing primordium growth.

Question 16

Atresia

Answer 16

Absence of an opening (usually hollow visceral organs e.g. trachea, intestine, bile duct).

Question 17

Hypoplasia

Answer 17

Decreased cell numbers –> incomplete development or decreased size of an organ.

Question 18

Hyperplasia

Answer 18

Increased cell numbers –> overdevelopment or increased size of an organ.

Question 19

Hypotrophy

Answer 19

Decreased cell size –> organ abnormality.

Question 20

Hypertrophy

Answer 20

Increased cell size –> organ abnormality.

Question 21

Dysplasia

Answer 21

Abnormal organisation of cells.

Question 22

Genetic causes of congenital abnormalities

Answer 22

• Chromosomal syndromes (10 - 15%).
• Mendelian inheritance (2 - 10%).

Question 23

Genetic causes of congenital abnormalities:
-Example of Mendelian inheritance

Answer 23

Holoprosencephaly (abnormal development of brain) secondary to loss of Hedghog signalling.

Question 24

Environmental causes of congenital abnormalities

Answer 24

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.

Question 25

What does a positive AChE stain indicate and what disease is this seen in

Answer 25

Indicates: * Indicates loss of ganglion cells (nerve cells in colon). Seen in: * Hirschsprungs.

Question 26

Malformations: Lymphatic malformation: *-What is it, how can it be identified histologically and why*

Answer 26

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.

Question 27

What is Foetal Hydrops, and what are some common causes?

Answer 27

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.

Question 28

Which region of the intestine is usually involved in necrotising enterocolitis

Answer 28

Ileocaecal region (vascular "watershed")