Congenital Defects

Question 1

Holoprosencephaly

Answer 1

• spectrum of structural abnormalities of the brain and face due to incomplete division of the forebrain (prosencephalon) into 2 hemispheres. - Cleavage of the prosencephalon into the telencephalon and diencephalon normally occurs at 5 weeks gestation
• Failure of cleavage at different points in division can result in an array of anomalies ranging from mild midline defects (eg, ocular hypotelorism, cleft lip/palate) to severe defects (eg, single midline eye, primitive nasal structure or proboscis, midfacial clefts).

caused by a combination of genetic (eg, trisomy 13, sonic hedgehog gene mutations) and environmental (eg, maternal alcohol use) factors.

an example of a developmental field defect, which is when an initial embryonic disturbance leads to multiple malformations by disrupting the development of adjacent tissues and structures within a particular region.

Question 2

Agenesis

Answer 2

complete absence of an organ.

Question 3

association

Answer 3

• multiple anomalies without a known unifying cause that occur together more frequently than chance alone would predict.
• Vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities (VACTERL)

Question 4

Deformations

Answer 4

fetal structural anomalies that occur due to extrinsic mechanical forces
- The pressure applied by the uterus is one of the most common deforming forces.

For example, uterine constraint on a fetus in breech position can cause developmental dysplasia of the hip, a condition marked by abnormal development of the femoral-acetabular junction and subsequent hip instability.

Question 5

Dysplasia

Answer 5

abnormal organization of cellular architecture within a tissue.

Osteogenesis imperfecta, a skeletal disorder characterized by brittle bones that fracture easily, occurs with dysplasia of connective tissue due to absent or abnormal type I collagen.

Question 6

Hirschsprung disease

Answer 6

• arrest of migration of neural crest cells in which a segment of colon is deprived of ganglion cells.
• Since neural crest cells migrate caudally, the rectum is always involved
• The absence of ganglion cells in the colonic wall causes the affected segment to be narrowed because it cannot relax.
• The passage of intestinal contents through this area is difficult, and compensatory dilatation of proximal areas of the colon occurs.
• Newborns with Hirschsprung disease fail to pass meconium within 48 hours of birth
• also demonstrate other symptoms of intestinal obstruction, such as bilious vomiting and abdominal distention. The bowel is filled with stool, but the rectum is empty; the tone of the anal sphincter is usually increased. Rectal biopsy reveals an aganglionic segment of bowel.
• Neural crest cells start migrating to the intestinal wall very early during embryonic development
• give rise to ganglion cells of the submucosal (Meissner) and myenteric (Auerbach) plexi of the bowel wall.
• These parasympathetic ganglia are responsible for intestinal peristalsis.
• Neural crest cells move caudally along the vagal nerve fibers. They are present in the wall of proximal colon at 8th week of gestation and in the rectum by 12th week.