Downs, Edward, Patau, Turner's

Question 1

Downs syndrome (Trisomy 21) Ex and RF:

Answer 1

• Most common autosomal trisomy and the most common genetic cause of learning difficulties.
• Results in extra chromosome 21.
  RF: Increasing maternal age.

Question 2

Down syndrome PPx?

Answer 2

• Extra chromosome 21 may result from meiotic non-disjunction, translocation or mosaicism.
  Meiotic non-disjunction - MOST COMMON:
• due to an error at meiosis where a pair of chromosome 21 fail to separate, so one gamete has 2 chromosome 21s and one has none.
• Fertilisation of the gamer with two chromosome 21s give rise to zygote with trisomy 21.
• Incidence is linked with INCREASING MATERNAL AGE.
• After having one child with trisomy 21 due to non-disjunction, the risk of recurrence increases in those under 35yrs.

Question 3

Clinical presentation of Downs (Craniofacial)?

Answer 3

1) Round face and flat nasal bridge
2) Epicanthic folds
3) Brush-field spots in iris
4) Small mouth and protruding tongue
5) Small ears

Question 4

Other anomalies:

Answer 4

1) Hyperflexibility
2) Hypotonia
3) Short neck
4) Single palmar creases
5) CONGENITAL HEART DEFECTS (40%)
6) Hirschsprung disease
7) Duodenal atresia

Question 5

Long-term:

Answer 5

1) Delayed motor milestones
2) Moderate/severe learning difficulties
3) Short stature
4) Hearing loss - secretory otitis media
5) Visual impairment from cataracts
6) Squints
7) Increased risk of leukaemia
8) Alzheimer’s disease

Question 6

Diagnosis of Down’s syndrome?

Answer 6

Antenatal:
1) Combined test: Blood sample between 10-14 weeks looking at free hCG and PAPP-A, ultrasound scan to ensure nuchal translucency (amount of fluid under skin at back of neck), mothers age. This is able to detect 86% of Trisomy 21. Also detects Edward’s and Patau’s.
2) Quadruple test: Blood test at 16 weeks looking at maternal serum hCG unconjugated estriol, alpha-fetoprotein and inhibin levels: only DOWNS.
3) Amniocentesis (amniotic fluid sampled) or chorionic villous sampling (placenta samples): Offered if you have a high chance result. DIAGNOSTIC but carries risk of miscarriage.
At BIRTH:
1) Blood sample sent for rapid FISH (fluorescent in situ hybridisation) at birth - parents need to be informed.

Question 7

Treatment for Downs?

Answer 7

All newborns should undergo screening for cardiac, feeding, hearing, thyroid, vision, haematological abnormalities ASAP.

1) Heart - 50% have congenital heart defects so ECHO essential (exclude VSD/TOF).
2) Feeding - radiographic swallowing assessment (exclude duodenal atresia)
3) Hearing - 90% have sensorineural, conductive or mixed loss.
4) TFT’s including TSH - as many have hypothyroidism
5) Vision - Red reflex testing to check for congenital cataracts

Physiotherapy - avoid child developing abnormal compensatory movements for physical limitations e.g. hypotonia, weakness, short limbs relative to trunk.

Occupational therapy - Facilitate development of fine motor skills and mastering self-help skills fo independence including feeding, dressing, writing and playing.

SALT.

Question 8

Edward’s syndrome (Trisomy 18) Ex, Sx, Dx?

Answer 8

• Second most common trisomy (trisomy 18).
• Extensive and characteristic congenital malformations - most affected babies die in infancy.

Sx:

1) Low birth weight
2) Micrognathia (undersized jaw)
3) Low-set ears
4) Rocker bottom feet and overlapping of fingers
5) Small mouth and chin, short sternum
6) Cardiac and renal malformations

Dx:

1) Combined test
2) Chromosome analysis
3) Amniocentesis/Chorionic Villous sampling (2nd trimester)

Question 9

Patau syndrome (Trisomy 13) Sx:

Answer 9

1) Cleft lip + palate
2) Polydactyly
3) Structural defects of brain
4) Cardiac and renal malformations
5) Scalp defects and small eyes

Dx:

1) Combined test
2) Chorionic villous sampling or amniocentesis (2nd trimester)

Question 10

Turner syndrome Ex, PPx?

Answer 10

FEMALES ONLY
Presence of only 1 sex chromosome (X) or a deletion of the short arm of one of the X chromosomes - denoted as 45X or 45 XO.
RF: Does NOT increase with maternal age.
PPx - 50% have 45 chromosomes with only 1 X chromosome, rest have deletion of the short arm of one chromosome.

Question 11

Presentation of Turner’s syndrome?

Answer 11

1) Lymphoedema of the hands and feet in neonates (May persist).
2) Short stature - CARDINAL
3) Neck webbing/thick neck
4) Delayed puberty
5) Widely spaced nipples
6) Congenital heart defects (coarctation of aorta)
7) Ovarian dysgenesis (infertility)
8) Hypothyroidism
9) Recurrent otitis media
NORMAL INTELLECTUAL FUNCTION

Question 12

Ddx of Turner’s syndrome?

Answer 12

NOONAN SYNDROME - hypertrophic cardiomyopathy, pulmonary stenosis, chest wall deformity and mental retardation (NOT IN TURNERS)

Question 13

Diagnosis of Turner’s syndrome?

Answer 13

1) ANTENATAL ULTRASOUND - foetal oedema of the neck, hands and feet.

Question 14

Treatment of Turner’s syndrome?

Answer 14

1) Growth Hormone - Somatropin
2) Oestrogen replacement - Estradiol (for secondary sexual characteristics in puberty)

Increased incidence of autoimmune disease (thyroiditis and Crohn’s)
All females are infertile but pregnancy with donor embryo possible.