Dysmorphology

Question 1

What is dysmorphology? Who primarily practices it?

Answer 1

Branch of clinical genetics specializing in birth defects, studies the etiology and pathogenesis of abnormal morphogenesis.

It is primarily practiced by clinical geneticists

Question 2

What is the leading cause of pediatric morbidity and mortality?

Answer 2

Birth defects -> affects 3-4% of children

Question 3

What are the four categories of congenital anomalies?

Answer 3

1. Malformations
2. Deformations
3. Disruptions
4. Dysplasias

Question 4

What is a malformation and give an example?

Answer 4

Defect in the morphogenesis / development of an organ or structure, usually occurring before 10 weeks gestation (very early)

i.e. syndactylyl, neural tube defects (spina bifida), hypoplasia of an organ

Question 5

What is a deformation and give an example?

Answer 5

Alteration in shape, position, or structure of a body part which was PREVIOUSLY NORMAL - caused via mechanical forces.

Example: clubfoot, craniofacial asymmetry

Question 6

What is arthrogryposis and what causes it?

Answer 6

Congenital joint contractions, caused via oligohydramnios or other amniotic cavity compression.

Question 7

What is a disruption and what causes it? Give an example.

Answer 7

Destruction of tissue that was previously normal, caused by factors extrinsic to developing structure.

For instance, amniotic bands (fibrous bands of amnion) can constrict the fingers and cause loss of finger growth. Can also result from vascular insufficiency, trauma, or teratogens.

Question 8

What is a dysplasia and what is it a subcategory of?

Answer 8

Abnormal cellular organization within tissue (single tissue type) resulting in structural changes, i.e. achondroplasia, since cartilage was previously forming normally.

It is a subcategory of deformations.

Question 9

What is a sequence? Give an example with spina bifida?

Answer 9

A pattern of multiple defects resulting from a single primary pathophys mechanism.

Club foot (talipes equinovarus) and hydrocephalus can result from a neural tube defect due to changes in innervation and CSF pressure

Question 10

What is the Pierre Robin sequence?

Answer 10

Restriction of mandible growth before 9th week can cause glossoptosis (tongue lies more posteriorly than normal) and cleft palate as a result.

Question 11

What is Potter sequence associated with?

Answer 11

Oligohydramnios

Question 12

What is an association? Give an example

Answer 12

A non-random occurrence of several anomalies which is not well understood or identified.

Example: VACTERL association
3 or more of the following: vertebral anomalies, anal atresia, cardiac, tracho-esophageal, renal, limb

Question 13

What is a major vs minor anomaly? What do you have to consider for minor?

Answer 13

Major - impairs normal body function, often requiring surgery - i.e. cleft palate or congenital heart defect

Minor - little or no surgical, medical, or cosmetic significance, but occur in <5% of population i.e. epicanthal folds.

For minor: consider also the race of the patient

Question 14

Why are minor anomalies important?

Answer 14

They can serve as markers for malformation, and patterns of these minor anomalies can suggest a syndromic diagnosis

Question 15

How common are minor anomalies?

Answer 15

15% of people have 1 minor, 1% have 3+, and having 3+ gives you a 20% chance of having an associated major anomaly.

Question 16

What is a teratogen and when is it most destructive?

Answer 16

A drug, infection, or environmental agent that causes birth defects, most destructive during critical developmental periods

Question 17

If exposed later, did thalidomide cause only lower limb or upper limb defects?

Answer 17

Only lower limb defects, since upper limb critical period is earlier

Question 18

What makes a major birth defect cause easy or hard to identify?

Answer 18

Hard - 60%, affecting only one organ system

Easy - affect multiple organ systems or accompanied by minor anomalies which indicate a “syndrome”

Question 19

What is a single gene syndrome? Give an example which results from defect of FGFR2 gene

Answer 19

Syndrome caused by a single gene defect.

Apert syndrome - craniosynostosis, underdeveloped midface, syndactylyl

Question 20

What type of syndrome is DiGeorge?

Answer 20

Microdeletion / microduplication class -> it is a 22q11 microdeletion syndrome.

Question 21

What type of disorders cause club foot and how common is this?

Answer 21

Polygenic / multifactorial, hard to identify the inheritance. This makes up about 50% of syndromes

Question 22

What are the features of fetal alcohol syndrome?

Answer 22

Growth restriction, microcephaly, cognitive impairment, characteristic facial features

Question 23

What does congenital rubella syndrome cause?

Answer 23

Micrcephaly, petechiae, heart disease, glaucoma, cataracts, small eyes

Question 24

What are the characteristics of holoprosencephaly?

Answer 24

Failure of forebrain to completely separate into two hemispheres, leads to clefting, hypotelorism (narrow-set eye distance) / cyclopia, pituitary dysfunction and developmental delay

Question 25

What is a single gene causes of holoprosencephaly?

Answer 25

Loss of Sonic Hedgehog. Autosomal dominant, leads to variable phenotype within the family, some of which only have a single incisor as the minor anomaly.

Question 26

What is a chromosome abnormality causing holoprosencephaly?

Answer 26

Trisomy 13

Question 27

What factor in pregnancy can lead to holoproencephaly?

Answer 27

Maternal diabetes

Question 28

What is the general idea of a genetic evaluation? What’s in it?

Answer 28

Get a complex genetic background and family history including 3 generations, maternal conditions and prenatal exposures, as well as postnatal history + physical exam in order to order the best genetic tests to determine what the genetic syndrome is rather than widely scanning

Question 29

What are some of the challenges in making a diagnosis even if your analysis is good?

Answer 29

Features tend to change overtime, and some may not have emerged yet in your syndrome. Some conditions are rare or not well described, and have variable expressivity.

Question 30

What do you want to do with a diagnosis once you have it?

Answer 30

1. Appropriate management and surveillance
2. Accurate prognostication and understanding of prognosis
3. Accurately assessing recurrence risk for parents.