Genetics/The Dysmorphic Child

Question 1

What is the Aetiology of Trisomy 21?

Answer 1

95% Non-disjunction
4% unbalanced translocation
1% Mosaic (mildest)

Question 2

What is an unbalanced translocation and what other chromosome is involved in unbalanced translocation in Down’s Syndrome?

Answer 2

Unbalanced translocation is when translocation results in extra or missing genetic material.
In Down’s this is usually with chromosome 14

Question 3

What is Brachycephaly?

Answer 3

Flat Occiput

Question 4

What are brushfield spots

Answer 4

White spots arranged in a ring around the pupil

Question 5

What is Cinodactyly? Where is it seen?

Answer 5

Shortened digit (usually 5th)
T21 and Russel-silver syndrome

Question 6

You are asked to examine a patient with down syndrome. what do you expect to see when examining the hand (2)?

Answer 6

Single palmer crease
Cinodactyly

Question 7

You are asked to examine a patient with down syndrome. what do you expect to see when examining the foot (2)

Answer 7

Sandle foot (Widely separated 1st and 2nd metatarsal)
Increased skin creases

Question 8

You are asked to examine a patient with down syndrome. what do you expect to see when examining the head (2)

Answer 8

Microcephaly
Brachycephaly

Question 9

You are asked to examine a patient with down syndrome. what do you expect to see when examining the eye (5)?

Answer 9

Brushfield spots, cataracts, squints, Upslanted palpebral fissure, Epicanthic folds

Question 10

You are asked to examine a patient with down syndrome. what do you expect to see when examining the ear (1)?
What is the significance of this finding?

Answer 10

Low set ears (also seen in turner’s)

Short Eustachian tube => increased risk of otitis media. Many have chronic otitis media.

Question 11

How would you know if ears are low or high set ears or just normal?

Answer 11

Draw an imaginary line from the corner of the eye to the ear where normally, 1/3 of the pinnaabove line

Question 12

You are asked to examine a patient with down syndrome. what do you expect to see when examining the nose (1)

Answer 12

Flattened nasal bridge (gives rise to pseudohypertelorism)

Question 13

You are asked to examine a patient with down syndrome. what do you expect to see when examining the mouth (1)
What is a complication that can arise from this finding?

Answer 13

Small mouth microstomia with protruding tongue
Sleep apnea

Question 14

How do measure the mouth

Answer 14

draw vertical lines from the pupils down. That is a normal mouth. Bigger = macrostomia, smaller, microstomia

Question 15

You are asked to examine a patient with down syndrome. what do you expect to see when examining the chin (1)

Answer 15

micrognathism

Question 16

How do you measure the size of the chin?

Answer 16

Must be on the same plane as the forehead. If it is too small, its micrognathism, big it is prognathism.

Question 17

What congenital heart disease can be found in many patients with Down’s? Explain it. How would you confirm this?
What effect would this have on the lungs?

Answer 17

AVSD: Atrioventricular septal defect
This is when there is a gap in the septum between the left and right side of the heart which allows blood to flow from the left to right side of the heart.
May cause pulmonary hypertension
ECHO

Question 18

List complications associated with down syndrome with tests on how to confirm if present (list 5)

Answer 18

Delayed developmental milestones
High level of autoimmunity => Hypothyroidism (Hashimoto) => hypothyroidism (TFTs/TSH)
AND Coeliac Disease => Coeliac screen
Obstructive sleep apnea
Atlantoaxial instability
Duodenal Atresia
Hirschprung Disease
Congenital Heart Disease (AVSD) => ECHO
Acquired hip dislocation (X-ray)
Type 1 DM

Question 19

What is Duodenal Atresia

Answer 19

abnormally closed or absent orifice in the duodenum

Question 20

What is Hirchprung Disease?

Answer 20

Congenital disease with missing nerves to the large intestine causing atresia.

Question 21

What investigations would you consider for a patient with down’s syndrome? (5)

Answer 21

FISH/RTPCR (real time PCR)
Specific growth charts for Down’s
Screen for hypothyroidism and Celiac Disease
Eye Examination at 4-6 weeks and 18-24 months
ECHO
Free glucose
Xray

Question 22

How would you confirm a Dx of down syndrome
1) Antenatally
2) Postnatally

Answer 22

1) NIPT - Non-invasive prenatal testing (blood test) or Amniocentesis
2) RTPCR or FISH

Question 23

Define
Plagiocephaly
Scaphocephaly
Frontal Bossing

Answer 23

Plagiocephaly: Flat in one area (not occiput => Brachycephaly
Scaphocephaly => Premature fusion
Frontal Bossing: Prominent

Question 24

What is the medical term for eyebrows that meet in the middle?

Answer 24

Synophrys

Question 25

What is the medical term for eyes that are wide apart?

Answer 25

Hypertelorism

Question 26

While examining a patient you notice blue sclera what is this a sign of? What is the inheritance of this disease

Answer 26

Osteogenesis imperfecta (AD)

Question 27

In terms of dysmorphic child, what syndrome has a prominent nose as a characteristic feature?

Answer 27

Rubinsteini Taybi Syndrome

Question 28

When examining an ear, you notice a skin tag on the tragus. What is this associated with?

Answer 28

Goldenhar Syndrome

Question 29

What is the Philtrum? What syndrome is it missing in?

Answer 29

What you thought was the nasolabial fold. It is in the midline above your upper lip. Missing in Foetal alcohol syndrome

Question 30

What is the medical term for small mouth? Where is it seen?

Answer 30

Microstomia in Down's Syndrome.

Question 31

You inspect a child with a cleft lip/palate what doe you suspect?

Answer 31

Trisomy 13, di George

Question 32

What is the medical term for small chin. Big? Where is it seen?

Answer 32

Micro/PROgnathism Down Syndrome

Question 33

While inspecting a patient you notice that her neck extends wider than usual. What is this finding and where is this characteristically found?

Answer 33

Webbing of the neck found in Turner's Syndrome and Noonan's

Question 34

While inspecting a patient you notice an absent thumb. What syndrome is this associated with?

Answer 34

Fanconi Syndrome

Question 35

While inspecting a patient, you ask them to fan out their fingers and notice that two fingers on the right hand are not separating as well on the left. What is this clinical finding and what is it associated with?

Answer 35

Syndactyly, Trisomy 18

Question 35

What inheritence is tuberosclerosis

Answer 35

Autosomal dominant

Question 36

What inheritence is neurofibromatosis Type 1:

Answer 36

Autosomal dominant

Question 37

What inheritence is cystic fibrosis

Answer 37

Autosomal recessive

Question 38

What is the inheritence of hemophilia, colour blindness, and muscular dystrophy

Answer 38

Recessive X-linked

Question 39

What is the inheritence of beta thallasemia and sickle cell anemia

Answer 39

Autosomal recessive

Question 40

What is the inheritence of hypophosphatemic rickets

Answer 40

X-linked dominant

Question 41

What are the cardinal features of Turner Syndrome

Answer 41

Short Stature, infertility, webbed neck, coarctation of the aorta, widely spaced nipples, aortic stenosis,

Question 42

How is Fragile X syndrome Diagnosed?

Answer 42

Trinucleotide repeat expansion in gene FMR1 via molecular analysis.

Question 43

What is the normal inheritance of these trinucleotide repeat disorders Fragile X Syndrome Friedriech ataxia Most others

Answer 43

Most of these triplet repeat disorders are autosomal dominant except Friedrich ataxia which is autosomal recessive and fragile X syndrome which is Xlinked recessive

Question 44

What are some clinical features associated with Fragile X-Syndrome (at least 5)

Answer 44

Note: These are most evident in an adult Moderate-severe learning difficulty Macrocephaly Macroorchidism (large testes) Characteristic Facies: Long face, !!large everted ears!!(also in Digeorge's if 22:11), Prominent mandible and forehead.

Question 45

Define "Imprinting"

Answer 45

It is when the expression of some genes are different based on the sex of the individual that has given you that gene. e.g. Failure to receive the functioning gene from the father will give you Prader Willi (therefore 2 maternal genes) and failure from the mother will give you Angelman (therefore 2 paternal genes).

Question 46

What are some clinical features associated with Prader Willi Syndrome (5)?

Answer 46

Hypotonia Hypogonadism characteristic facial features (almond eyes, triangular mouth) Neonatal feeding difficulties but hyperphagia in adulthood Faltering growth in infancy (short stature) Developmental delay and learning difficulties

Question 47

A baby is delivered and you notice that they are hypotonic. What 2 syndromes are you suspecting (genetics)

Answer 47

Down's Syndrome Prader Willi Syndrome

Question 48

What is the most common mode of inheritance.

Answer 48

Polygenic so if you dont know, say this especially if there is a quantitative component.

Question 49

What are some clinical features of Noonan's (give 3)?

Answer 49

Webbing of neck (also in turner) Pectus Excavatum short stature congenital heart disease (ASD, pulmonary stenosis)

Question 50

What is Iris Coloboma

Answer 50

Key-ring pupil, looks like it is oozing out.