Genetic Syndromes - Down's, Turner's, Edwards, Patau, William's, Fragile X

Question 1

Antenatal testing in Downs
-combined test
-quadruple test
-test interpretation
-further testing

Answer 1

Combined test - 11-13+6wks
-Nuchal translucency
-bHCG
-PAPPA

Downs
-high HGC
-low PAPPA
-thickened nuchal translucency

Quadruple test - 15-20wks
-aFetoprotein
-unconjugated estriol
-HCG
-inhibin A

Downs
-low aFetoprotein, estriol
-high HCG, inhibin A

Results are
-lower chance - 1 in 150 or more
-higher chance - 1 in 150 or less

Higher chance => NIPT/CVS/amniocentesis

NIPT
-sensitivity and specificity v high for Downs

CVS - 11-13wks
Amniocentesis - 15wks onwards

Question 2

Presentation of Down’s Syndrome on inspection

Answer 2

Face
-upslanted palpebral fissures
-flattened nasal bridge and face => repeated resp infections
-epicanthal fold
-low set small ears
-short neck
-brushfield spots in iris

Hands - single palmar crease

Feet - sandal gap

General - hypotonia
-floppy ligaments => atlantoaxial instability

Question 3

Down’s syndrome
-cardiac/hematological complications
-GI complications
-endocrine complications

Answer 3

Atrioventricular canal
VSD
ASD
TOF
PDA
ALL

Duodenal atresia
Hirschsprung’s disease

Hypothyroidism

Question 4

Down’s syndrome
-development differences

Answer 4

Shorter stature => own growth chart

Global delay in meeting developmental milestones

Question 5

Chromosomal disorders in
-Down’s
-Turners

Answer 5

Down’s = Trisomy 21
Edward’s = Trisomy 18
Patau = Trisomy 13

Turners = 45 XO
Noonan = defect on C12

Fragile X = trinucleotide repeat disorder on X

William’s = microdeletion on C7

Question 6

Presentation of Turner’s on inspection

Answer 6

Short stature
Shield chest, widely spaced nipples
Webbed neck
Low hairline
Many moles
High arched palate

Question 7

Complications of Turner’s
-cardiac
-endocrine
-renal
-lymphatic
-AI

Answer 7

Cardiac => increased risk of aortic dilation and dissection
-bicuspid aortic valve
-coarctation of aorta

Endocrine
-primary amenorrhea
-high GnRH
-hypothyroidism

Renal
-horseshoe kidney

Lymphatic
-cystic hygroma - malformation of lymphatic system, painless, soft, translucent lump

AI
-AI thyroiditis
-Crohns

Question 8

Patau Syndrome
-antenatal screening result - combined screening
-key features

Answer 8

11-13+6 weeks
-thick nuchal translucency
-low bHCG and PAPPA

Microcephaly, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions

Question 9

Edwards’s Syndrome
-antenatal screening result - combined screening
-key features

Answer 9

11-13+6 weeks
-thick nuchal translucency
-low bHCG and PAPPA

Micrognathia
Low-set ears
Rocker bottom feet
Overlapping fingers
Severe intellectual disability

Question 10

Fragile X
-diagnosis
-presentation in males
-presentation in females

Answer 10

Antenatally
-CVS
-amniocentesis
Postnatally
-genetic testing

Males
Inspection
-macrocephaly
-large, low set ears
-long thin face
-high arched palate
-macroorchidism
-hypotonia

Cognitive
-learning difficulties
-autism common

Cardiac
-mitral prolapse

Females
-features range from normal to mild

Question 11

Noonan syndrome
-features on inspection
-cardiac + hematological

Answer 11

Male Turner’s - AD on C12

Features on inspection
-webbed neck
-widely spaced nipples
-short stature
-ptosis
-triangular shaped face
-low set ears

Cardiac
-pulmonary valve stenosis
-Factor 11 deficiency => hemophilia

Question 12

William’s syndrome
-features on general inspection

Answer 12

Features
-elf like
-short stature

Cognitive
-learning difficulties

Endocrine
-transient neonatal hypercalcemia

Cardiac
-supravalvular aortic stenosis