GENETIC SYNDROMES/MULTI SYSTEM CONDITIONS

Question 1

MOST common associations with PATAU syndrome (Trisomy 13)

Answer 1

Holoprosencephaly (40-50%)
Polydactyly (70%)

Question 2

Of the three most common trisomies which one has the highest incidence of major structural anomalies?

Answer 2

18 - Edwards syndrome

Question 3

What are the most common findings of trisomy 18

Answer 3

CHD (90-95%)
CNS or spinal abnormalities (70%)
- choroid plexus cyst, agenesis of CC
- Dandy walker continuum
- Neural tube defects (20%) spina bifida (myelomeningocele)
IUGR (60-90%) seen early
Cystic hygroma (20%)
clenched hand over overlapping 2nd/3rd digits (80%)
Single umbilical artery (80%)
Omphalocele (20-25%)

Question 4

DOWNS syndrome - most common cause?

Answer 4

meiotic non disjunction - 95% of cases

Question 5

Downs have increased incidence of what cancer

Answer 5

Leukaemia - AML

Question 6

What are the 3 ways triploidy 69 chromosomes occurs?

Answer 6

Failure of division of meiosis I or II in the sperm
Failure of division of meiosis I or II in oocyte
Dispermy - fertilisation of one egg by 2 sperms.

Question 7

What is the clinical triad of Aicardi syndrome ?

Answer 7

x-linked genetic defect - FATAL in males
salaam seizures
CC dysgenesis
Chorioretinal Lacunae - pathognomonic

Question 8

MOST common cause of hereditary cholestasis ?

Answer 8

Alagille syndrome
JAG1 mutation 90%

Question 9

MOST common genetic cause of emphysema and metabolic liver disease.

Answer 9

A1-AT deficiency
basal predominant panlobular emphysema

Question 10

Ataxia Telangiectasia has increased risk of which cancers?

Answer 10

bowel and breast

Question 11

MOST common overgrowth and cancer predisposition syndrome? What cancers are it associated with?

Answer 11

Beckwith Wiedemann syndrome
Wilms
hepatoblastoma
neuroblastoma
rhabdomyosarcoma

Question 12

MOST common associations of Crouzon syndrome

Answer 12

Chairi I (70%)
Stylohyoid ligament calcification >4yrs (50%)

Question 13

Classical TRIAD of HHT and most common locations

Answer 13

Epistaxis
Multiple telangiectasias
Positiev Family History

Question 14

Most common associations with Joubert syndrome

Answer 14

MCDK (30%)
Polydactyly (15%)
Coloboma, retinal dysplasia

Question 15

Maffuci syndrome is more common in males but associated with what 2 conditions?

Answer 15

Juvenile Granulosa tumour of the ovary
Colorectal haemangioma

Question 16

What condition has a triad of multiple renal cysts, occipital encephalocele and polydactyly?

Answer 16

Meckel Gruber syndrome

Question 17

What are the 2 most common RASopathy’s

Answer 17

NF1 and Noonan syndrome

Question 18

What is an autosomal recessive disorder of euthyroid goitre and associated with senorineural hearing loss ? MOST common cause of syndromic hearing loss and accounts for >10% of hereditary deafness?

Answer 18

Pendred syndrome

Question 19

autosomal dominant genetic abnormality and results from bilateral malformations of first and second branchial arches

Answer 19

Treacher Collins syndrome

Question 20

extremely rare lethal form of congenital muscular dystrophy and almost always shows fetal hydrocephalus

Answer 20

Walker-Warburg syndrome (WWS), sometimes known as HARDE syndrome

Question 21

What is the MOST common lethal genetic disease in caucasians?

Answer 21

CYSTIC FIBROSIS

Question 22

MOST common infections seen in CF?

Answer 22

Burkholderia cepacia
Pseudomonas aeruginosa - biofilm

Question 23

What are the findings of LEFT isomerism ?

Answer 23

polysplenia
azygous/hemizygous continuation of the IVC
bilateral HYPOarterial bronchi
Bilateral bilobed lungs
Bilateral pulmoanry/left atria
midline/transverse liver
intestinal malrotation

Question 24

What are the findings of RIGHT isomerism ?

Answer 24

Asplenia
Severe Cyanotic CHD
Bilateral eparterial bronchi
Bilateral trilobed lungs
Bilateral right atria
Midline/transverse liver
interstinal malrotation

Question 25

What is the MOST common brain malformation and the 3 subtypes

Answer 25

HOLOPROSENCEPHALY
Alobar
semilobar
lobar

Question 26

Triad of
situs inversus
sinusitis/nasal polyps
bronchiectasis

Answer 26

Kartagener syndrome

Question 27

primary defect is a retrognathic mandible which occurs at 7-11 weeks of gestation due to abnormal development of the first pharyngeal arch. Characterised by

micrognathia
glossoptosis
posterior cleft palate or high arched palate

Answer 27

Robin sequence

Question 28

CHARGE syndrome stands for
If this is suspected patients should have what imaged?

Answer 28

Coloboma
Heart defects
Atresia Choanea
retarded growth
genital hypoplasia
ear abnormalities/deafness

CT temporal bones
MRI brain

Question 29

complex congenital anomaly characterised by abnormalities of the ears, eyes and vertebrae.

Answer 29

Goldenhar syndrome

Question 30

rare congenital condition characterised by the absence or underdevelopment of the nuclei of the abducens (CN VI) and facial nerve (CN VII).

Answer 30

Mobius syndrome

Question 31

Unilateral absence of pectoralis major and minor muscles

Answer 31

Poland syndrome

Question 32

rare congenital malformation characterised by the fusion of lower limb structures.

Answer 32

Sirenomelia

Question 33

CREST syndrome stands for

Answer 33

CREST syndrome (also known as limited systemic sclerosis or limited scleroderma) is a variant of progressive systemic sclerosis (PSS) and stands for

C - calcinosis
R - Raynaud phenomenon
E - oesophageal dysmotility
S - sclerodactyly
T - telangiectasia

Question 34

autoimmune connective tissue disorder characterised by multisystem fibrosis and soft tissue calcification

What are pathognomonic findings

Answer 34

Scleroderma, also known as systemic sclerosis
More common in females

hidebound bowel and dilatation of the distal 2/3rds of the eosophagus

Clinical manifestation depends on which systems are predominantly involved. It should be noted that the majority of patients 70-97% develop an arthropathy that mostly affects the fingers, wrists, and ankles 3,5. Oesophageal involvement is common, occurring in approximately 80% of patients 5. Although 90% of patients have pulmonary involvement histologically, only a minority are symptomatic

Question 35

Serological markers for Scleroderma
MOST common ones that are positive

Answer 35

antinuclear antibodies (ANA): 35-96%
anti-Scl-70 antibodies: 30-70% (particularly in diffuse disease)
rheumatoid factor- positive in 30-40%
anti-centromere antibodies: 20-40% (particularly in limited disease)
ESR

Question 36

What systems are commonly involved in Scleroderma?

Answer 36

MSK - acro-osteolysis
subcutaneous and periarticular calcs
GI - eosophagus 80%
- Small bowel (duodenum) 80%
- LB 40%
- Stomach - rare
Renal - 25% - HTN and acute renal failure

Question 37

What does PHACE syndrome stand for

Answer 37

P: posterior fossa malformations (e.g. Dandy-Walker malformation)

H: haemangiomas

A: arterial anomalies

C: coarctation of the aorta and cardiac anomalies

E: eye (ocular) anomalies

Question 38

What does VACTERL stand for ?

Answer 38

V: vertebral anomalies
hemivertebrae
congenital scoliosis
caudal regression
spina bifida
A: anorectal anomalies
anal atresia
C: cardiac anomalies; cleft lip
TE: tracheo-oesophageal fistula +/- oesophageal atresia
R: renal anomalies; radial ray anomalies
L: limb anomalies
polydactyly
oligodactyly