Genetics

Question 1

Guthrie Card Age and Tests

Answer 1

Day 5-9 once feeding established 
Cards Help Medics To Pick up Sickness
Cystic Fibrosis
Hypothyroidism
Sickle Cell Anaemia
Thalaessaemia 
Phenylketonuria
MCAD deficiency

Question 2

Purpose 24h routine check newborn

Answer 2

1) Detect congen abnormalities not detected at birth e.g. CnHD, developmental dysplasia of hip
2) Check for potential problems arising from maternal disease/ family disorders

Question 3

Median birthweight of newborn

Answer 3

3.5kg

Question 4

Lesions in newborns that resolve sponteneously

Answer 4

Periph cyanosis of hands and feet (common 1st day)
Traumatic cyanosis
Subconjunctival haemorrhages (occur during delivery)
Breast enlargement
Epstein’s pearls (small white pearls along midline of palate)
White vaginal d/c or small w/dwal bleed
Capillary haemangioma
Neonatal urticaria
Milia (white pimples on nose/ cheeks)
Mongolian blue spots
Umbilical hernia (normally resolves in 2-3y, no tx)
Positional talipes

Question 5

Sig abnormalities detected on routine newborn exam

Answer 5

Portwine stain
Strawberry naevus
Front lower incisors
Extra digits
Heart murmur 
Midline abnormality over spine/ skull
Palpable or large bladder
Talipes equinovarus

Question 6

RFs DDH

Answer 6

Girls
Positive FHx
Birth is breech
Infant has NM disorder

Question 7

Consequences vitamin K deficiency

Answer 7

Haemorrhagic disease of the newborn

Vit K def -> reduced production of coagulation factors

Question 8

Features haemorrhagic disease of newborn

Answer 8

Disorder can occur early (during 1st week) or late (1-8 wks)
Most affected infants mild (bruising, haematemesis, melaena, prolonged bleeding umbilical stump)
Severe: ICH -> permanent disability or death in 1/2

Question 9

RFs HDN

Answer 9

Formula = rich
Breast milk = poor (HDN can occur in purely breastfed infants)
Increased risk in mothers taking AEDs
Infants w liver disease

Question 10

Prevention HDN

Answer 10

Vitamin K injection (IM immediately after birth)
Can be given orally: 3 doses in first 4 weeks
Mothers on AEDs: oral prophylaxis from 36 weeks and IM injection to newborn straight after birth

Question 11

MCAD

Answer 11

Medium-Chain-Acyl CoA- def
Rare inborn error of fatty acid metabolism
Causes acute illness + hypoglycaemia after fasting
May also present as acute life-threatening episode

Question 12

Screening for CF

Answer 12

Measure serum immunoreactive trypsin (raised if pancreatic duct obstruction)
If raised -> DNA analysis (reduce false +ve rate)

Question 13

Newborn hearing screening

Answer 13

Universal screening
Evoked otoacoustic emission testing
|f EOAE abnormal, test with automated auditory brainstem response audiometry
If abnormal -> refer to paediatric audiologist

Question 14

Amniocentesis age

Answer 14

> 15 weeks

Question 15

CVS age

Answer 15

> 10 weeks

Question 16

Amniocentesis can test for

Answer 16

Foetal infection (PCR)
Chromosome: trisomy 21/18/13, fragile X
DNA analysis: CF, sickle cell, Duchenne, haemophilia
AFP and Ach for neural tube defects
Bilirubin: rhesus disease
Enzyme analysis: inborn errors metabolism

Question 17

Foetal blood sampling can test for

Answer 17

Foetal Hb for anaemia
Foetal infection serology
Foetal blood transfusion

Question 18

CVS can test for

Answer 18

Chromosome/ micro-array and DNA analysis
Foetal infection (PCR)
Enzyme analysis of inborn error of metabolism

Question 19

Preimplantation genetic diagnosis

Answer 19

IVF allowing genetic analysis of cells from developing embryo before transfering to uterus

Question 20

Fetoscopy

Answer 20

minimally invasive surgery e.g.laser photo-coagulation of communicating vessels in TTTS

Question 21

Free foetal DNA from maternal blood

Answer 21

Foetal gender

Rhesus status

Question 22

Antenatal screening

Answer 22

Down’s syndrome (all women >35)
Sickle cell disease: universal
Thalassaemia/ haemoglobinopathies: universal
Congen abnormalities: routine USS at 18-20 wks

Question 23

School entry screening

Answer 23

Vision: Snellen chart
Hearing: school entry sweep to detect progressive hearing loss

Question 24

Maternal antenatal bloods

Answer 24

Blood group, rhesus status + antibodies
Infection (Hep B/C, syphilis, rubella, HIV)
Neural tube defects (raised MAFP + USS)
Down’s syndrome (AFP + US)

Question 25

Maternal antenatal bloods pros and cons

Answer 25

Pro: safe, non-invasive Con: doesn't provide direct evidence re foetus

Question 26

US conditions screened

Answer 26

``` gestational age multiple pregnancy structural malformation (anencephaly, spina bifida, cardiac, diaphragmatic hernia, exomphalos/ gastroschisis, hydrops etc) foetal growth oligohydramnios/ polyhydramnios ```

Question 27

Amniocentesis pros and cons

Answer 27

Pro: genetic level screening, screening for inborn errors of metabolism Con: invasive, small chance miscarriage (1%), can only be done after 15 wks

Question 28

CVS pros and cons

Answer 28

Pros: can be performed v early in pregnancy (9-12 wks) Cons: invasive, risk miscarriage 1-2%, infection, bleeding

Question 29

Down's syndrome genetics

Answer 29

95% Trisomy 21 4% translocation 1% mosaicism

Question 30

Incidence Down's syndrome

Answer 30

1/650 births

Question 31

Craniofacial features Down's

Answer 31

``` Round face, flat nasal bridge Upslanted palpebral fissures (eyelids) Epicanthic folds Brushfield spots Small ears Small mouth, protruding tongue Flat occiput and 3rd fontanelle ```

Question 32

Other anomalies Downs

Answer 32

``` Short neck Single palmar creases Wide sandal gap Hypotonia CnHD (40%) Duodenal atresia Hirschsprung's disease ```

Question 33

Downs late medical problems

Answer 33

``` Delayed motor milestones Mode-severe learning difficulties Small stature Infection susceptibility Hearing + visual impairment Epilepsy Hypothyroidism Leukaemia risk Alzheimers disease ```

Question 34

Turner's syndrome genetics

Answer 34

45X

Question 35

Antenatal identification Turner's

Answer 35

Oedema of neck/ hands/ feet

Question 36

Tx Turner's

Answer 36

Growth hormone and oestrogen at time of development of 2y sexual characteristics

Question 37

Turner's clin signs

Answer 37

``` Wide spaced nipples Shield chest Wide carrying angle Short stature (cardinal feature) Lymphoedema of hands and feet in neonate Thick neck/ neck webbing ```

Question 38

Complications Turner's

Answer 38

``` CnHD: aortic coartation Delayed puberty Ovarian dysgenesis -> infertility Hypothyroidism Renal abnormalities Normal intellectual function in most ```

Question 39

William's syndrome genetics

Answer 39

Deletion long arm chromosome 7

Question 40

Clin features William's syndrome

Answer 40

``` WILLIAMS Weight: low at birth, slow to gain Iris: stellate iris Long philtrum Large mouth Increased Ca2+ Aortic stenosis (and other stenoses) Mental Retardation ("cocktail party chatter") Swelling around eyes ```

Question 41

Fragile X genetics

Answer 41

Trinucleotide expansion in FMR1 gene

Question 42

Fragile X clin features

Answer 42

``` Males more severely affected vs females Delayed dvpmnt speech/ language by age 2 Mild-moderate intellectual disability (M>F) 1/3 features ASD, others attention def disorder Seizures (15%) Macro-orchidism (post-pubertal) Macrocephaly Lax joints ```

Question 43

Fragile X facies

Answer 43

Long, narrow face Large ears Prominent jaw and broad forehead (Unusually flexible fingers, flat feet, enlarged testes)