Syndromes And Genetics

Question 1

What is the most common underlying cause of Turner syndrome?

Answer 1

Nondysjunction in father as X is usually from mum

Question 2

What form of Turner syndrome is more associated with learning disability?

Answer 2

Ring X

Question 3

Physical appearance of Turner syndrome?

Answer 3

Short stature, increased weight
Webbed neck (cystic hygroma)
Low set ears
Low posterior hairline
Broad shield chest and widely spaced nipples
Short 4th metacarpals, small fingernails

Question 4

What is thought to cause the webbed neck in Turner syndrome?

Answer 4

Cystic hygroma

Question 5

What sign at birth might suggest Turner syndrome?

Answer 5

Lymphoedema - swollen hands and feet

Question 6

What is notable about the arms in Turner syndrome?

Answer 6

Wide carrying angle

Question 7

What hormonal changes occur in Turner syndrome?

Answer 7

Anovulation and amennorhoea (hypo GnRH)
Often low T4 Hashimoto’s
DM 1 and 2 incidence both increased

Question 8

What heart problems occur in Turner syndrome?

Answer 8

Aortic valve stenosis
Bicuspid aortic valve
Coarctation of aorta
PAVD

Question 9

What do most 45XO foetuses do in utero?

Answer 9

Spontaneously terminate in 1st trimester

Question 10

How is Noonan syndrome inherited?

Answer 10

AD

Question 11

What is the most common underlying genetic defect causing Noonan syndrome?

Answer 11

RASopathy - mutations in the Ras/MAPK signalling pathways

Question 12

What common syndrome is thought to have a risk of malignant hyperthermia and/or poor anaesthesia clearance associated with it?

Answer 12

Noonan syndrome

Question 13

3 heart findings in Noonan syndrome?

Answer 13

Pulmonary stenosis
ASD/VSD
Hypertrophic cardiomyopathy

Question 14

2 skin/lymph findings in Noonan syndrome?

Answer 14

Lymphoedema 
Webbed neck (cystic hygroma)

Question 15

What may occur in boys with Noonan syndrome?

Answer 15

Cryptorchidism

Question 16

What are the most common bleeding disorders that occur in Noonan syndrome?

Answer 16

Amegakaryocytic thrombocytopenia
vDW
APTT prolongation
Factor deficiencies

Question 17

What malformation of brain is associated with Noonan syndrome?

Answer 17

Arnold chiari type 1

Question 18

What facial appearance may suggest Noonan syndrome?

Answer 18

Webbed neck
Hypertelorism
Epicanthal folds
Low set backwards rotated ears
Deeply grooved philtrum, micrognathia, high arched palate

Question 19

What is the technical term for wide carrying angle?

Answer 19

Cubitus valgus

Question 20

What is the most common robertsonian translocation causing Down syndrome?

Answer 20

46XY;t(14q21q)

Question 21

What facial features suggest Down syndrome?

Answer 21

Slanted eyes and epicanthal folds
Flat nasal bridge
Small mouth, macroglossia
Short neck

Question 22

What nocturnal respiratory does Down syndrome carry and why?

Answer 22

OSA - relatively large tongue for small mouth which can block airway

Question 23

What hands and feet changes occur in Down syndrome?

Answer 23

Single palmar crease

Big gap between 1st and 2nd toe

Question 24

What neck problem occurs in Down syndrome?

Answer 24

Atlanto-axial joint instability possibly leading to cord injury

Question 25

What eye sign is suggestive of Down syndrome?

Answer 25

Brushfield spots

Question 26

Heart problems associated with Down syndrome?

Answer 26

AVSDs Mitral valve problems ToF, PDA

Question 27

4 cancers that have higher risk in Down syndrome?

Answer 27

AML ALL Transient myeloproliferative disorders Testicular cancer

Question 28

What is the relative risk of solid organ tumours in people with Down syndrome?

Answer 28

Lower

Question 29

GI changes associated with Down syndrome?

Answer 29

``` Hirschprungs disease Duodenal atresia Pyloric stenosis Imperforate anus Meckel diverticulum GORD Coeliac ```

Question 30

What is the immune system like in Down syndrome?

Answer 30

Suppressed

Question 31

What thyroid disturbances are common in syndromes e.g. Down, turner?

Answer 31

Often low - Hashimoto's

Question 32

What is Pompe disease?

Answer 32

Glycogen storage disorder type 2 - acid maltase deficiency due to GAA gene mutation, causing hypotonia myopathy hepatomegaly and HOCM within first few months of life. Treatment is myozyme - recombinant human GAA

Question 33

What is the most common urea cycle defect?

Answer 33

OTC deficiency

Question 34

What is the most severe urea cycle defect?

Answer 34

CPS1 deficiency

Question 35

Give 3 organic acidaemias?

Answer 35

Methylmeluric aciduria Isovaleric acidaemia Maple syrup urine disease

Question 36

What kind of acid base disturbance and other metabolic disturbances feature in organic acidaemias?

Answer 36

Metabolic acidosis Ketotic hypglycaemia Raised ammonia

Question 37

What does VACTERL stand for?

Answer 37

``` Vertebral anomalies e.g. Butterfly vertebra Anorectal anomalies Cardiac defects TOF EOA Renal and radial abnormalities Limb defects ```

Question 38

What does 'smelly feet odour' in unwell neonate suggest?

Answer 38

Isovalaeric acidaemia

Question 39

What is primary HLH caused by?

Answer 39

AR gene mutations e.g. Perforin (PRF1)

Question 40

3 things which might underlie secondary HLH? Particular infection?

Answer 40

Strong infection e.g. EBV Immunodeficiency Malignancy

Question 41

What is HLH?

Answer 41

Cytokine storm disease characterised by uncontrolled proliferation and activation of lymphocytes/macrophages

Question 42

When does HLH typically occur?

Answer 42

Within 1st year of life

Question 43

What might typical signs and symptoms of HLH be?

Answer 43

``` Rash Jaundice Fever HSM Lymphadenopathy ```

Question 44

What bone marrow picture does HLH cause?

Answer 44

Hypocellular causing low e.g. RBCs, neutrophils, platelets

Question 45

What does HLH show on blood/lymph/marrow film?

Answer 45

Haemophagocytosis

Question 46

What 3 blood markers might be altered in HLH?

Answer 46

Raised triglycerides Low fibrinogen Raised ferritin

Question 47

Cure fo HLH?

Answer 47

BMT

Question 48

What does CHARGE syndrome stand for?

Answer 48

``` Coloboma Heart defects Atresia of choana Retardation of growth and development Genital abnormalities Ear abnormalities ```

Question 49

What underlies CHARGE syndrome?

Answer 49

AD inheritance of CHD7 mutation | Causes failure of growth of midline structures during 2nd month of gestation

Question 50

6 syndromes which may feature radial abnormalities?

Answer 50

Thrombocytopenia-absent radius syndrome (TAP) VACTERL Edwards syndrome Cornelia de Lange syndrome Fanconi anaemia Valproate or thalidomide exposure in utero

Question 51

What is the Pierre Robin sequence?

Answer 51

Micrognathia leading to glossoptosis leading to airway obstruction Often in the setting of cleft palate

Question 52

4 syndromes associated with Pierre Robin sequence?

Answer 52

Fetal alcohol syndrome Stickler syndrome Di George/velocardiofacial syndrome Treacher Collins syndrome

Question 53

What is Stickler Syndrome?

Answer 53

AD collagen disorder causing flattened face with Pierre Robin sequence, underdeveloped midface High myopic eyes, abnormal vitreous and cataracts/glaucoma Hearing loss Other hypermobility, scoliosis and MSK features etc.

Question 54

What is Treacher Collins syndrome?

Answer 54

AD craniofacial disorder associated with Pierre Robin, downward slanting eyes with lower lid coloboma and abnormal ears/hearing loss

Question 55

What is Moebius syndrome?

Answer 55

Congenital absence of CNS 6 and 7 plus or minus 5, 9, 10 and 12 Plus upper body weakness, dental problems/high palate, syndactyly, hearing problems

Question 56

What is Haddad syndrome and what gene is associated?

Answer 56

Ondine's curse plus Hirschprungs disease in setting of PHOX2B mutation

Question 57

What is the pentalogy of Cantrell?

Answer 57

``` Exomphalos Cleft sternum Anterior diaphragmatic hernia Heart defects incl ectopia cordis Pericardial agenesis ```