Screening

Question 1

Routine infectious disease screens?

Answer 1

HIV
Syphilis
Hep B
Thalassaemia

Question 2

When is the anomaly scan?

Answer 2

Weeks 18-21

50% of Downs syndrome children will show features on US (cardiac defects)

Question 3

Which test happens in weeks 10-14?

Answer 3

Trisomies 13, 18, 21

Question 4

What makes up the combined test in the 1st trimester?

Answer 4

1) Maternal age
2) Nuchal translucency (12 weeks)
3) Gestational age from foetal length (CRL)
4) PAPP-A, free beta-hCG

Question 5

Combined test results for T18 and T13:

Answer 5

High NT (higher in 18)
Low beta-hCG (lower in T18)
Low PAPP-A (both lower than in T21)

Question 6

Combined test results for T21:

Answer 6

High NT
High beta-hCG
Low PAPP-A

Question 7

If screening is +ve, offer diagnosis. What are the diagnostic methods and the corresponding weeks?

Answer 7

<15 weeks = CVS

>16 weeks = amniocentesis

Question 8

What is NIPT?

Answer 8

Non-invasive prenatal testing

Used for detecting anueploidies (T13, 18, 21)

Question 9

What is NIPD?

Answer 9

Non-invasive prenatal diagnosis
Rhesus D
Y chromosome
Dominant disorders (FGFR2+3 for skeletal dysplasias)
Recessive disorders (Duchenne - RHDO)

Question 10

What does RHDO mean?

Answer 10

Relative haplotype dosage

Question 11

Protocol with HIV +ve mother?

Answer 11

Reduce viral load and prevent transmission

Question 12

Protocol with mother with Hep B?

Answer 12

Vaccinate neonate

Question 13

Protocol with syphilis?

Answer 13

Treat mother to prevent congenital syphilis

Question 14

Criteria for chromosome abnormality screening?

Answer 14

Offer to everyone between 11+0 and 13+6 weeks gestation

Question 15

Which group gets pre-conceptual - 10 week screening?

Answer 15

Those at high risk of sickle and thalassaemia

Question 16

US - Acrania:

Answer 16

12 weeks = absence of ossified skull

16 weeks = encephalopathy

Question 17

US - Alobar holoprosencephaly:

Answer 17

Forebrain abnormalities in transverse views associated with T13 and T18 in >50% of cases and 20% associated with genetic syndromes

Question 18

US - Spina bifida:

Answer 18

Open lemon and banana sign

Closed by surgery

Question 19

US - Cleft lip and palate:

Answer 19

11-13 weeks

30% associated with genetic syndrome

Question 20

US - Diaphragmatic hernia:

Answer 20

20% associated with T13 or T18
10% associated with other genetic syndromes
20% associated with other system defects
Therapy = fetoscopic placement of balloon in trachea at 26 weeks

Question 21

What are the only chromosomes viable in an aneuploidy state?

Answer 21

13, 18, 21, X and Y

Question 22

What are the two types of chromosomal translocation?

Answer 22

Robertsonian

Reciprocal

Question 23

Robertsonian translocation can only occur with which chromosomes?

Answer 23

Acrocentric chromosomes

13, 14, 15, 21 and 22

Question 24

Common Robersonian translocations?

Answer 24

der(13;14) is the most common

der(14;21) is next most common, female carriers of which have a 15% risk of a T21 pregnancy

Question 25

Reproductive risks of balanced Robertsonian translocations?

Answer 25

Recurrent miscarriages Patau syndrome (T13) Downs syndrome (T21) Male infertility

Question 26

What is QF-PCR used for?

Answer 26

Aneuploidy and sexing

Question 27

What is aCGH used for?

Answer 27

Detecting genomic imbalance across the genome

Question 28

What is G-banded chromosome analysis used for?

Answer 28

Confirmation of aCGH result and for follow up

Question 29

What is FISH in metaphase used for?

Answer 29

Confirmation of aCGH result and for follow up

Question 30

What is FISH in interphase used for?

Answer 30

To detect unbalanced products of a known familial balanced rearrangement

Question 31

What is mutation testing or sequencing used for?

Answer 31

To test for monogenic disorders

Question 32

Patau syndrome:

Answer 32

``` T13 or unbalanced transloc: 46Xn + 13,der(13;14)(q10;q10) XX Cleft lip and palate Holoprocencephaly Post-axial polydactyly (toe) Renal problems Cardiac problems Severe mental disability 45% die within 1 month, 85% within 1 year ```

Question 33

What is holoprocencephaly?

Answer 33

Failure of the embryonic forebrain to separate into two hemispheres

Question 34

Edward's syndrome:

Answer 34

``` T18 XX or XY Severe mental disability Micrognathia Clenched fingers Cardiac defects Prominent heels and rocker-bottom feet ```

Question 35

Downs syndrome:

Answer 35

``` 40% have cardiac defects Up-slanting features Clinodactyly (inward curving 5th finger/toe) Intellectual disability GI disorder Feeding problems Single palmar crease Hypotonic baby with hyper-extensible joints ```

Question 36

Noonan's syndrome:

Answer 36

Short stature, down-slanting features, poor growth CHD Pectus excavatum/carinatum Spine deformities Intelligence unaffected mostly Poor hearing, poor clotting Delayed puberty, undescended testes, male infertility

Question 37

What causes Noonan's syndrome?

Answer 37

Autosomal dominant mutation in gene involved in hyperactive Res signalling KRAS, BRAF, MEF, PTPN11

Question 38

Features of neurofibromatosis:

Answer 38

``` Cafe-au-lait spots Neurofibromas Bone defects Scoliosis Lisch nodules Glioma ```

Question 39

Crossover between NF type 1 and Noonan's:

Answer 39

Valvular pulmonary stenosis | Noonan-like facies aka Watson syndrome

Question 40

del22q11.2 =

Answer 40

``` CHD - conotruncal anomaly Cleft lip and/or palate Absent thymus and parotid glands Dysmorphic features and learning disabilities Motor and speech delay ASD Psychiatric disorder Polymicrogyria ```

Question 41

del7q11 =

Answer 41

``` William's syndrome: Facial differences Narrowed aorta and pulmonary arteries Hypertension Friendly and outgoing, anxious ADHD Scoliosis, bone and joint problems Kidney problems and UTIs Musical talent ```

Question 42

del16p11.2 =

Answer 42

``` Learning difficulties ASD Seizures and learning difficulties Schizophrenia, bipolar disorder and depression Obesity in young adults 25 gene deletion (can be unaffected) ```

Question 43

Autosomal recessive metabolic conditions:

Answer 43

Oculocutaneous albinism BBS (obese, neurodisability, kidney and retina problems) MPS

Question 44

X-linked:

Answer 44

Haemophilia Duchenne MD - onset at 3-6 years of age, progressive weakness, pseudo hypertrophy of calf muscles, cardiopulmonary involvement, spinal deformity

Question 45

What is detectable at 10-14 weeks?

Answer 45

Anencephaly

Question 46

When can you detect spina bifida?

Answer 46

By 16-22 weeks (lemon and banana sign)

Question 47

Higher serum maternal AFP correlates with...

Answer 47

Severity of neural tube defect

Question 48

Difference between myotonic dystrophy and congenital myotonic dystrophy?

Answer 48

The first is 3 repeats whereas the latter is 4 repeats | Congenital is more severe with respiratory failure, developmental delay and ASD