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.
who would be required in mx of Fragile X?
SALT
EHP - educational health plan - special school, teaching assistant support
May need Physio/OT - if scoliosis - rarer
what are the most common causes of intellectual disability?
- Downs syndrome - most common
- Fetal alcohol
- Other genetics eg Fragile X, PWS
what is the aetiology and presentation of NOONAN syndrome?
Auto Dom mutation. Normal karyotype.
- Severity varies from lethal prenatally to minimal morbidity
- No specific management except ↑ health surveillance
Clinically • Characteristic facies • Mild learning difficulties • Short webbed neck, low trident hair line • Pectus excavatum • Short stature • CHD • Vision, hearing, growth problems • Easy bruising and bleeding
which syndrome is associated with Transient neonatal hypocalcaemia?
Williams
what is the aetiology of PWS - PRADA WILLI?
- Imprinting → expression is influenced by the sex of parent who has transmitted it
- Lack of paternal copy of PWS chromosomal region → PWS
loss of maternal copy does NOT cause PWS
Also; de novo deletion in the child of region on Chr 15 or uniparental disomy
what is the presentation of PWS syndrome?
- Hypotonia
- Developmental delay
- FTT (in infancy, obesity in later childhood) - may present with short stature in chihldhood
• Feeding difficulties - early in life followed by
• Hyperphagia - later
• Learning difficulties)
- undescended testicles
what is the management of PWS syndrome?
Feeding difficulties:
Dietitians and speech and language therapists can help with advice about what feeds to give and how to encourage your baby to feed.
Dietician advice about diet to prevent excess weight gain
Exercise plans
Starting treatment with Somatotropin GH is usually recommended during early childhood, from 6 months to 2 years of age, and normally continues until the end of growth.
-increases muscle strength and energy levels
Behavioural difficulties and tantrums
- NHS website give many helpful tips
Skin picking
- CBT
Orchidopexy - if indicated
May have vision/sleep and other problems as they grow - NHS website for info, but come back to see us if any develop.
Prader-willi syndrome association UK
what is Duchenne muscular dystrophy DMD?
Aetiology ?
A muscular dystrophy (progressive weakness and breakdown of skeletal muscle + eventually death)
• X linked recessive frameshift deletion, resulting in lack of dystrophin production
Either inherited from mother or De novo mutation
Its caused by a mutation of the dystrophin gene at locus Xp21, on the X chromosome.
Dystrophin is responsible for connecting the actin cytoskeleton of each muscle fiber to the underlying basal lamina
Loss of dystrophin = Muscle fibers undergo necrosis and are ultimately replaced with adipose and connective tissue!!
What are the clinical signs of DMD?
• Asymptomatic at birth usually but then
Presents often in first 5 years of life with decreased motor milestones and progressive weakness
- Delayed walking, falls, difficulty climbing stairs, clumsy, may have a waddling gait, contractures or scoliosis
- +/- toe walking, muscle pain, decreased endurance, pseudohypertrophy of calves (replaced by fat and fibrous tissue)
- Decreased tone and power
- Positive Gower’s sign – when child uses their hands to climb up their legs when rising from the ground
- May have delayed speech or global developmental delay
- DMD causes a primary dilated cardiomyopathy (DCM) + Heart Failure and conduction abnormalities (around teens)
Pulmonary function decline
