Genetics Flashcards
what are the characetristic facies seen in downs?
Round face, flat nasal bridge o Upslanting palpebral fissures o Epicanthic folds o Brushfield (pigmented) spots on iris o Small mouth and protruding tongue o Small eyes, flat occiput and third fontanelle
what are physical abnormalities seen in downs??
o Short neck
o Single palmar crease, wide ‘sandle gap’ between toes
o incurved 5th finger
o Hypotonia
name some Congential conditions seen in Downs?
o CHD (40%) → commonly ASD
o Duodenal atresia
o Hirschsprung disease
what are the consequences/complications of Downs?
o Delayed motor milestones
o Moderate to severe learning disabilities
o Short stature
o Increased susceptibility to infections
o Hearing impairment → secondary to otitis media
o Visual impairment → cataracts, squints, myopia
o Increased risk of leukaemia and solid tumours
o Risk of atlanto-axial instability
o Increased hypothyroidism, coeliac disease, epilepsy and Alzheimer’s
how do we ivx Downs?
Which are the most common genetic forms?
usually picked up antenatally
Karyotype - blood test + FISH - chromosomal analysis:
- Meiotic non-disjunction (94%)
- Translocation (5%)
- Mosaicism (1%)
Echo - heart conditions
US abdominal - GI conditions
What are the principles of management of DOWNS SYNDROME?
• Immediate
o Imaging - Echo and evaluation by paediatric cardiologist for CHD
o Genetic counselling (review chromosome results, discuss risk of recurrence) – recurrence usually 1% until maternal risk increases
o Early intervention programmes if developmental delay is present
▪ Physiotherapy → prevent abnormal compensatory movements for physical limitations
▪ OT → fine motor and self-care
▪ SALT → speech intelligibility and to manage language delay
• Later
o Appropriate education placement with an individualised educational plan
o Annual hearing evaluation, thyroid levels, ophthalmic evaluation (up to 5 years then every 2 years). Hb level for IDA
o Monitor for symptoms of sleep apnoea
o Monitor growth using updated Down’s syndrome growth charts
• Support
o Contact local DS clinic, access to local parent support groups
o Down syndrome association → helpline with lists of local groups, new parents pack, info for families and carers
o www.downsyndrome.org.uk
what are the clinical features of Edwards?
• Low birth weight or intrauterine growth restriction
• Prominent occiput
• Small mouth and chin
Cleft lip/Palate
- Short sternum
- Flexed overlapping fingers
- Rocker bottom feet
- Severe intellectual disability
• Cardiac 50% GI 75% and renal malformations
same 3 genetic mis-hap as downs
trisomy 18
list some congeital abnormalities present in Edwards?
CHD- Ventricular septal defect, atrial septal defect, patent ductus arteriosus
GI - Intestines protruding outside the body (omphalocele), esophageal atresia
Development - intellectual disability, developmental delays, growth deficiency
Others - feeding difficulties, breathing difficulties
what is the prognosis of Edwards?
95% dont result in live birth
of those that do, only 12% live to 1 year
only 1% live to 10 years
what are the clinical features of Patau’s?
• Structural defect of brain → holoprosencephaly (cyclops) - not all only some
- Scalp defects
- Small eyes and other eye defects
- Cleft lip and palate
- Polydactyl - 6 fingers
- Cardiac 80% and renal malformations
80% die within 1st month of life; 90% within first year
mum has kid with 1 of the above chromosomal disorders, what is the recurrence risk?
1% of this happening again
how may turners present?
• Short stature may be the only clinical abnormality • Lymphoedema of hands or feet in neonate • Koilonychia • Neck webbing • Wide carrying angle • CHD → coarctation of the aorta • Delayed puberty and primary amenorrhoea • Ovarian dysgenesis and infertility → but cando donor IVF • Hypothyroidism • Renal abnormalities • Pigmented moles • Recurrent otitis media
More than 95% result in early miscarriage.
how do we ivx and mx Turners?
IX: at time of diagnosis, child must have Echo, ECG,
MRI (for aorta)
Management:
• Growth hormone therapy
o Plot height on syndrome specific growth charts
• Oestrogen replacement
o At time of puberty for development of 2ndary sexual characteristics
how does kleinfelters commonly present?
MDT involvement?
- Infertility – most common presentation
- Hypogonadism and small testes
- Gynaecomastia in adult life
- Tall
- May have educational or psychological problems.
Requires neurological evaluation and endocrinology
referral.
47XXY
how does Fragile X commonly present?
CGG trinucleotide repeat expansion mutation.
X-Linked recessive.
A proportion of female carriers show learning difficulties!
Clinically:
• Main issues are with social interaction and Anxiety!
•They have similar sx/behaviour as seen in Autism but difference is they are v sociable once used to people.
They have bad anxiety in new environments and that when behavioural issues can arise.
- Largest genetic cause of autism
- They can present with ADHD type behaviour eg hyperactivity
•They have delay in achieving motor milestones eg speaking and walking but do achieve them eventually.
LARGE Ears may be the first prominent features
- Moderate to severe learning disability – mean IQ 50
- Large prominent ears
- Macrocephaly
- Macro-orchidism - large testes.
- Characteristic facies → long face, large ears, prominent mandible, broad forehead
- MV prolapse, joint laxity - hypermobile joints - which can cause issues, scoliosis.
