Screening Flashcards
Routine infectious disease screens?
HIV
Syphilis
Hep B
Thalassaemia
When is the anomaly scan?
Weeks 18-21
50% of Downs syndrome children will show features on US (cardiac defects)
Which test happens in weeks 10-14?
Trisomies 13, 18, 21
What makes up the combined test in the 1st trimester?
1) Maternal age
2) Nuchal translucency (12 weeks)
3) Gestational age from foetal length (CRL)
4) PAPP-A, free beta-hCG
Combined test results for T18 and T13:
High NT (higher in 18)
Low beta-hCG (lower in T18)
Low PAPP-A (both lower than in T21)
Combined test results for T21:
High NT
High beta-hCG
Low PAPP-A
If screening is +ve, offer diagnosis. What are the diagnostic methods and the corresponding weeks?
<15 weeks = CVS
>16 weeks = amniocentesis
What is NIPT?
Non-invasive prenatal testing
Used for detecting anueploidies (T13, 18, 21)
What is NIPD?
Non-invasive prenatal diagnosis Rhesus D Y chromosome Dominant disorders (FGFR2+3 for skeletal dysplasias) Recessive disorders (Duchenne - RHDO)
What does RHDO mean?
Relative haplotype dosage
Protocol with HIV +ve mother?
Reduce viral load and prevent transmission
Protocol with mother with Hep B?
Vaccinate neonate
Protocol with syphilis?
Treat mother to prevent congenital syphilis
Criteria for chromosome abnormality screening?
Offer to everyone between 11+0 and 13+6 weeks gestation
Which group gets pre-conceptual - 10 week screening?
Those at high risk of sickle and thalassaemia
US - Acrania:
12 weeks = absence of ossified skull
16 weeks = encephalopathy
US - Alobar holoprosencephaly:
Forebrain abnormalities in transverse views associated with T13 and T18 in >50% of cases and 20% associated with genetic syndromes
US - Spina bifida:
Open lemon and banana sign
Closed by surgery
US - Cleft lip and palate:
11-13 weeks
30% associated with genetic syndrome
US - Diaphragmatic hernia:
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
What are the only chromosomes viable in an aneuploidy state?
13, 18, 21, X and Y
What are the two types of chromosomal translocation?
Robertsonian
Reciprocal
Robertsonian translocation can only occur with which chromosomes?
Acrocentric chromosomes
13, 14, 15, 21 and 22
Common Robersonian translocations?
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
Reproductive risks of balanced Robertsonian translocations?
Recurrent miscarriages
Patau syndrome (T13)
Downs syndrome (T21)
Male infertility
What is QF-PCR used for?
Aneuploidy and sexing
What is aCGH used for?
Detecting genomic imbalance across the genome
What is G-banded chromosome analysis used for?
Confirmation of aCGH result and for follow up
What is FISH in metaphase used for?
Confirmation of aCGH result and for follow up
What is FISH in interphase used for?
To detect unbalanced products of a known familial balanced rearrangement
What is mutation testing or sequencing used for?
To test for monogenic disorders
Patau syndrome:
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
What is holoprocencephaly?
Failure of the embryonic forebrain to separate into two hemispheres
Edward’s syndrome:
T18 XX or XY Severe mental disability Micrognathia Clenched fingers Cardiac defects Prominent heels and rocker-bottom feet
Downs syndrome:
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
Noonan’s syndrome:
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
What causes Noonan’s syndrome?
Autosomal dominant mutation in gene involved in hyperactive Res signalling
KRAS, BRAF, MEF, PTPN11
Features of neurofibromatosis:
Cafe-au-lait spots Neurofibromas Bone defects Scoliosis Lisch nodules Glioma
Crossover between NF type 1 and Noonan’s:
Valvular pulmonary stenosis
Noonan-like facies aka Watson syndrome
del22q11.2 =
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
del7q11 =
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
del16p11.2 =
Learning difficulties ASD Seizures and learning difficulties Schizophrenia, bipolar disorder and depression Obesity in young adults 25 gene deletion (can be unaffected)
Autosomal recessive metabolic conditions:
Oculocutaneous albinism
BBS (obese, neurodisability, kidney and retina problems)
MPS
X-linked:
Haemophilia
Duchenne MD - onset at 3-6 years of age, progressive weakness, pseudo hypertrophy of calf muscles, cardiopulmonary involvement, spinal deformity
What is detectable at 10-14 weeks?
Anencephaly
When can you detect spina bifida?
By 16-22 weeks (lemon and banana sign)
Higher serum maternal AFP correlates with…
Severity of neural tube defect
Difference between myotonic dystrophy and congenital myotonic dystrophy?
The first is 3 repeats whereas the latter is 4 repeats
Congenital is more severe with respiratory failure, developmental delay and ASD
