Genetics

Question 1

22q11.2 deletion

Answer 1

• Variable facial dysmorphism, Pierre Robin sequence, cleft palate
• Thymic hypoplasia with T-cell deficit -> immunodeficiency
• Parathyroid hypoplasia -> Hypocalcemia, seizures
• Conotruncal cardiac defects:
  – Interrupted aortic arch
  – Tuncus arteriosus
  – Tetralogy of Fallot
  – Double outlet RV
  – Pulmonary atresia

Diagnosis:
* 22q11.2 deletion, detectable by chromosome microarray or FISH testing.

Question 2

Prader Willi Syndrome

Answer 2

Infancy
* Low muscle tone
* Poor suck, FTT
* Hypogonadism
* Relatively larger forehead
* Narrow bifrontal area
* Down-turned mouth
* Almond-shaped eyes

Age >1yo
* Obesity and Hyperphagia
* Small hands and feet
* Developmental delay
* Mild ID
* Behavioral disturbances (temper tantrums, self-injurious behaviours, OCD)
* Skin picking
* Hypogonadism

Dx: Chromosome microarray or FISH and DNA methylation testing

Question 3

Williams Syndrome

Answer 3

• CV: Supravalvular aortic stenosis
• Long philtrum, “elfin” face, stellate iris
• Hyperextensibility
• Social seeking personality ‘cocktail party personality’
• Learning delays, mild-mod ID
• Infantile hypercalcemia

Diagnosis : 7q11.23 microdeletion (requires FISH)

Question 4

Kleinfelter syndrome

Answer 4

• Delayed sexual development
  – Hypogenitalism,hypogonadism
• Relatively long limbs, tall stature
• Intellectual deficiency
• Behavioural problems
• Gynecomastia

Diagnosis on karyotype (47XXY)

Question 5

NF 1 exam

Answer 5

• Vitals
  
  • Ask for blood pressure!
• Inspection: 4 Ss
  
  • Height (short)
  • HC (Macrocephaly)
  • Scars (spinal)
  • VP shunt to head
  • Facial asymmetry
  • Pubertal status (delayed or precocious)
  • MSK
    
    • Scoliosis
    • Lower limbs - thinking of lower limb bones, tibial bowing (pseudoarthrosis)
    • Asymmetry - hemihypertrophy or segmental hypertrophy (plexiform neurofibromas)
  • SKIN
    
    • CALM (6 or more)
    • Axillary freckling
    • Neurofibromas (2 or more)
• Eyes
  
  • Visual fields
  • Proptosis/exopthalmous (eye bulging)
  • Ptosis (droopy eyelid)
  • Mention slit lamp for lisch nodules
  • Mention fundoscopy for optic nerve hypoplasia
• Chest/CV
  
  • BP
  • Murmur (coarctation - rad to back; pulmonary stenosis - both ES at ULSE)
• Abdo
  
  • Mass = pheochromocytoma
  • Renal bruits (renal artery stenosis) - Use bell, auscultate 2cm superior and just lateral to umbilicus
• Neuro
  
  • Gait
  • Full neuro exam if time
• Puberty
  
  • Delayed or precious

Question 6

NF 1 ix and screening

Answer 6

1. Genetics: NF1 (+/- SPREAD1) gene test or microarray for the diagnosis
2. Blood pressure
3. Head circumference
4. Scoliosis
5. Audiology RV
6. Opthal RV yearly
7. Cognitive and developmental ax
8. MRIB (?IC tumours/optic nerve glioma if suspected clinically)

Question 7

Achondroplasia complications

Answer 7

• Short stature (rhisomelic/overshooting, incr US:LS ratio)
• Macrocephaly
• Distinctive features: frontal bossing, midface hypoplasia
• Hypotonia as infant -> delayed GM milestones
• Spinal cord compression (spinal stenosis)
• Hydrocephalus
• Lumber lordosis
• Varus deformity of legs
• Recurrent OM
• Obesity

Question 8

T21 complications

Answer 8

CNS - Hypotonia, ID, GDD, behavioural problems
Hearing - Recurrent OM, CHL
Vision - impairment
ENT - enlarged tonsils, OSA due to hypotonia
Heart - AVSD, ASD, VSD
GI - duodenal and anorectal atresia, Hirschsprung, coeliac disease
Ortho - hip/patellar instability, atlantoaxial instability
Endo - thyroid disease
Haem - Leukaemia

Question 9

Turners cx

Answer 9

• CV: bicuspid AV, coA, HTN
• Renal anomalies (renal USS q5yr)
• Thyroid fun (hypothyroidism) - TFTs yearly
• Ears: SNHL - audiology yearly
• Eyes: risk of strabismus, ptosis
• Dental crowding and malocclusion
• OGTT (glucose intolerance)
• GI: coeliac disease screening Q2yrly
• Short stature: GH consideration
• Scoliosis
• Pubertal delay (90% have ovarian failure): may need induction
  -> endo referral for pubertal induction
  -> DEXA
  -> pelvic USS
• Fertility planning (may need assisted technology +/- C/S)
• M/H: support groups