Embryology- complications of development

Question 1

Define teratology.

Answer 1

Structure of a tissue has not developed appropriately. Can define what has gone wrong- what is the likely cause, know what the mother was exposed to, can look at what has happened and deduce where it went wrong.

Question 2

Define birth defect/ congenital malformation/ congenital abnormality.

Answer 2

Something has gone wrong during the developmental process.

Question 3

Define dysmorphology.

Answer 3

Altered basic shape of a tissue or structure. Equivalent to teratology.

Question 4

What proportion of pregnancies are affected by major abnormalities?

Answer 4

About 3%.

Question 5

What proportion of infant deaths are caused by major developmental abnormalities?

Answer 5

25%.

Question 6

What proportion of pregnancies are affected by minor abnormalities?

Answer 6

About 15%.

Question 7

What are the major causes of developmental abnormalities in pregnancy?

Answer 7

Genetic- 30%.

Environmental- 15%.

Multifactorial- 55%.

Question 8

Define teratogen.

Answer 8

Any agent that can disturb the development of an embryo or foetus.

Question 9

What infectious agents can cause developmental abnormalities in pregnancy?

Answer 9

Rubella virus: cataracts, glaucoma, heart defects, deafness, teeth

Herpes simplex virus: microphthalmia, microcephaly, retinal dysplasia

HIV: microcephaly, growth restriction

Syphilis: mental retardation, deafness

Zika virus: microcephaly

Question 10

What physical agents can cause developmental abnormalities in pregnancy?

Answer 10

X-rays and other ionising radiation: microcephaly, spina bifida, cleft palate, limb defect.

Question 11

What chemical agents can cause developmental abnormalities in pregnancy?

Answer 11

Thalidomide: limb defects, heart malformations

Lithium: heart malformations

Amphetamines: cleft lip and palate, heart defects

Cocaine: growth restriction, microcephaly, behavioural abnormalities

Alcohol: foetal alcohol syndrome, maxillary hypoplasia, heart defects

Question 12

What are the broad categories of external causes of developmental abnormalities in pregnancy?

Answer 12

Teratogens

Infectious agents

Physical agents

Chemical agents

Question 13

How can differences in chromosome distribution cause developmental abnormalities?

Answer 13

Mosaicism (nondisjunction)- differences between cells within one individual.

Distribution of cells between inner cell mass and trophectoderm (placenta).

Chimerism- fused multiple zygotes (non-identical zygotes).

Question 14

Give an example of a developmental abnormality resulting from too many chromosomes, XY linked.

Answer 14

Kleinfelter’s syndrome (XXY)- decreased fertility.

XXYY, XXXY, XXXYY, etc.- severe forms related to KS.

XYY (XYYY)- very variable (taller, learning problems).

XXX- limited effects, some mental changes.

XXXX, XXXXX- more severe effects.

Question 15

Give examples of developmental abnormalities resulting from too many chromosomes, autosomal.

Answer 15

Down’s syndrome (ch21):

• 1/1000 live births
• heart problems determine survival

Edward’s syndrome (ch18):

• 1/6000 live births
• most die before birth, very few live-born, live <2 weeks.

Patau’s syndrome (ch13):

• 1/15,000 live births
• most die before birth, 80% live-born die within 1 year

Others not found in live birth, most detected in some spontaneous pregnancy loss tissues.

Ch1 trisomy not found in pregnancy loss tissues.

Question 16

Give an example of a developmental abnormality resulting from too few chromosomes, XY linked.

Answer 16

Turner’s syndrome- X0:

• female, short stature, infertile
• Y0 not viable.

Question 17

What results from a developmental abnormality resulting from too few chromosomes, autosomal.

Answer 17

No complete losses are viable.

Partial chromosome loss syndromes known and characterised/

Question 18

Give an example of a developmental abnormality resulting from altered distribution of chromosomes, XY linked.

Answer 18

‘XX male’- XY translocation.

Question 19

Give an example of a developmental abnormality resulting from altered distribution of chromosomes, autosomal.

Answer 19

Linked with development of tumours, lymphoma, leukaemia, sarcoma.

Question 20

What is Holt-Oram syndrome?

Answer 20

Atrial septation defects

Range of hand abnormalities

Phenotype due to mutation in TBX5 (transcription factor)- required as both structures develop

Question 21

What is achondroplasia?

Answer 21

Gain of function mutation in FGFR3.

Achondroplasia means ‘lack of cartilage’.

Defect is in conversion of cartilage to bone and lack of bone growth.

Question 22

Describe the process of limb development in utero, with timings.

Answer 22

Forelimb bud appear at d27/8.

Hindlimb bud at d29.

Grow out from lateral plate mesoderm rapidly under control of special signalling regions.

Fully formed and patterned by d56.

Question 23

What are 3 forms of spina bifida?

Answer 23

Spina bifida occulta (hidden, hairy)

Meningocele

Myelomeningocele

Question 24

What is the incidence of spina bifida?

Answer 24

1-2 per 1000 pregnancies.

Question 25

What are the benefits of surgery for spina bifida?

Answer 25

Can help anatomically but not with functional neurological problems.

Question 26

How and when does spina bifida occur?

Answer 26

Development of bony part of spine is driven by neural tissue.
No bone forms over the region.
Faulty neurulation (posterior neuropore).
Occurs in the first 4 weeks after fertilisation.

Question 27

How does folic acid in diet influence spina bifida?

Answer 27

Decreases incidence by around 70%. Should be given 3 months before conception.

Question 28

What is anencephaly and its incidence?

Answer 28

‘Headless’- top part of the head doesn’t develop properly, ‘top end’ spina bifida.
Anterior neuropore closure incomplete.
Incidence: 1-8 per 10,000 births.
Female babies affected more commonly than male.
Occurs about 23 days post-fertilisation.

Question 29

What are the effects of thalidomide on pregnancy and foetal development?

Answer 29

~10,000 affected infants known, ~50% initial survival rate.

Limbs affected- effects on upper limbs most common, but lower limbs and internal organs can also be affected.

In addition, deformed eyes and hearts, deformed alimentary and urinary tracts, blindness and deafness.

Used in some leprosy and cancer treatments at present.

Affects rapidly developing blood vessels, notably those of upper limbs.

Blood vessel effects can be generic, hence the range of effects observed.

Question 30

What is the polarising factor for limb development?

Answer 30

Sonic hedgehog (shh).