Paediatric Genetics Flashcards
How do children normally get the additional chromosome in Down syndrome?
Additional chromosome 21 is commonly maternally derived from non-dysjunction
What screening tests should a baby with Down syndrome have done?
Cardiac echo Feeding assessment - radiographic Vision - red reflex as risk of cataracts Thyroid - TSH and free T3/T4 Hearing - 90% have some level of hearing loss
What is the average life expectancy of a Down syndrome baby and how do they commonly die?
50yo
Most die of respiratory infection
What features of the head are indicative of Down syndrome?
Dysmorphic round face Down slanting palpebral fissure Flat nasal bridge Epicanthic folds Brushfield spots on iris Small, low set ears Flat occiput - brachycephaly Protruding tongue - not macroglossia
What neck features are indicative of Down syndrome?
Abundant neck skin
Atlantoaxial instability
Hypothyroidism
What limb features are indicative of Down syndrome?
Incurved little fingers
Single palmar crease
Gap between 1st and 2nd toes
What other features are classical with Down syndrome?
Dislocations Increased risk of leukaemia Cardiac defects - 50% Resp. infections GI problems Alzheimers disease
What cardiac defects are seen in Down syndrome?
VSD
Patent ductus arteriosus
ASD
What GI problems are seen in Down syndrome?
Duodenal atresia - double bubble on AXR
Higher risk of: GORD Hirschprung's Meckel's Coeliac
What is the place of antenatal screening in Down syndrome?
Its an optional screening program offered to all women
Should be counselled about the tests, risks, accuracy and what Down syndrome is
What is the aim of antenatal screening for Down syndrome?
Identify women at higher risk and offer further diagnostic testing
What further diagnostic testing can be done for Down syndrome?
Chrorionic villus sampling if <13 weeks
Amniocentesis if >15 weeks
What is the outcome of antenatal screening for down syndrome?
Expert counselling
Support
Offer termination
What is the process of antenatal screening for Down syndrome?
Serum free B-hCG (raised in Downs baby)
PAPP-A (lower in Downs baby)
USS to measure fetal nuchal translucency - increased in chromosomal abnormalities and heart failure
What is turners syndrome?
Loss or abnormality of an X chromosome in at least 1 cell line in a phenotypic female
45X
What 2 features characterise turners syndrome?
Short stature
Primary amenorrhoea
What features of turners syndrome would you see in a newborn?
Lymphoedema of hands and feet
Excessive skin at nape of neck
What features of turners syndrome would you see in an infant?
Feeding difficulty
Poor weight gain
What other dysmorphic features are indicative of turners?
Webbed neck
Wide spaced nipples
Wide carrying angle
High arched palate
Epicanthic folds with downturned palpebral fissures
Pectus excavatum
Hearing loss - sensorineural/ottitis media with effusion
What structural and functional abnormalities are seen in turners syndrome?
Gonadal dysgenesis
Congenital heart disease - coarctation, bicuspid aortic valve
Renal anomalies - absent, horseshoe or malrotated
Specific learning and behavioural disabilities
Hypertension
Autoimmune disorders
How is diagnosis of turners syndrome made?
Prenatal - US scan
Birth appearance
Childhood changes
Adolescence
Diagnosis confirmation by chromosomal analysis
How is turners syndrome managed?
MDT for all systems
Screening - thyroid, coeliac, hearing, ECG/echo
Bone age
Growth hormone therapy - in childhood - not if fused epiphysis
Oestrogen therapy - adolescence
Fertility - oocyte donation or embryo transplant
What inheritance pattern is Duchenne Muscular Dystrophy?
X linked Recessive
Only affect males
New mutations are common so not all female relatives are carriers
How common is Duchenne Muscular Dystrophy?
1 in 4000 males
What is the pathophysiology of Duchenne Muscular Dystrophy?
Lack of dystrophin –> increased Ca entry into cell –> oxidative stress –> damage to sarcolemma and eventual cell death
What does dystrophin normally do?
Connect muscle fibres to basal lamina - stabilise the plasma membrane
What happens in the short term in Duchenne Muscular Dystrophy?
Muscles regenerate but fibres different sizes
What eventually happens in Duchenne Muscular Dystrophy?
Myocyte apoptosis and creatine kinase release leads to a progressive muscle atrophy.
Fat and fibrotic tissue infiltrates muscle for pseudohypertrophy
How does Duchenne Muscular Dystrophy present?
Symptoms occur by 3 years usually Delay in development Pseudohypertrophy of calf and tongue Gower's sign Waddling gait or tiptoe walking Speech delay Fail to thrive
What parts of the body are affected in what order in Duchenne Muscular Dystrophy?
1 Hips, pelvis, thighs, shoulders
2 Arms, legs, trunk
3 Cardioresp
What are some later effects of Duchenne Muscular Dystrophy?
Severe muscle weakness - wheelchair bound by 10-14yo Type 2 resp failure Scoliosis Contractures Dilated cardiomyopathy Fatigue Some may have learning disabilities
How is Duchenne Muscular Dystrophy diagnosed?
Watch child!
Creatinine kinase raised (eventually drop)
Genetic testing
Muscle biopsy
What is important to be aware of with Duchenne Muscular Dystrophy and anaesthetics?
DMD patients offer experience malignant hyperthermia and cardiac problems so anaesthetic use req. close monitoring
What differentials may you consider for Duchenne Muscular Dystrophy?
Beckers muscular dystrophy - milder, progress more slowly
Polymyositis
Neurological causes - MS, spinal cord lesions etc.
What is the general management for Duchenne Muscular Dystrophy?
MDT approach
Inform and support
Genetic diagnosis and counselling
Immunisations - flu and pneumococcal
What is the management for children <11yo with Duchenne Muscular Dystrophy?
Physio
Knee-foot-ankle orthoses, serial casting ankles
Steroids - oral prednisolone
Calcium and vit D supplements
What is the management for children with DMD between 8-11yo (once lost ability to walk)?
Mobility aids
Surgery for scoliosis
Cardiac and resp surveillance
What is the management for the later stages of Duchenne Muscular Dystrophy?
Palliative care
Respire for family
End of life directives
What respiratory complications are seen with Duchenne Muscular Dystrophy?
Hypoventilation - start during sleep
Lose cough - resp infections
Resp failure - often cause death
What are the cardiac complications seen in Duchenne Muscular Dystrophy?
Cardiomyopathy
Congestive heart failure
Arrhythmias
What gastro problems are seen in Duchenne Muscular Dystrophy?
Pseudo-obstruction
What is important for the parents if their child has Duchenne Muscular Dystrophy?
Genetic counselling
Pre-natal genetic testing for subsequent pregnancies
They have increased risk of cardiomyopathy
Why may carriers of Duchenne Muscular Dystrophy get skeletal muscle symptoms?
X-inactivation
Symptoms can be mild or as severe as DMD
