Genetics / Metabolics

Question 1

What is the mode of inheritance of neurofibromatosis type 1?

Answer 1

Autosomal dominant

Question 2

What is the diagnostic criteria for NF1?

Answer 2

2+ of the following:
6 hyperpigmented cafe au lait macules (5mm in children, 15mm post puberty)
2+ neurofibromas or 1 plexiform neurofibroma
Axillary or inguinal freckling (late childhood)
Optic glioma (< 10yo)
2+ Lisch nodules (iris hamartomas, < 20yo)
Tibial pseudoarthrosis or sphenoid dysplasia
First degree relative with NF1

Question 3

What is the recommended surveillance for NF1?

Answer 3

• Monitor growth, HC, BP
• Skin exam annually
• Bone or scoliosis exam annually
• Neurological exam annually
• Ophtho exam annually
• Monitor for precocious puberty
• Diagnostic imaging as needed

Question 4

What investigations are indicated for a child with William’s syndrome?

Answer 4

• Microarray
• ELN molecular gene testing
• Serum ca and urine ca
• TFTs
• Echo
• AUS + doppler’s for RAS
• Audiology
• Ophthalmology

Question 5

What testing should be done in a child with suspected Turner syndrome?

Answer 5

• Karyotype
• LH/FSH elevated, estradiol is low
• TFT
• Echo
• RBUS
• Ophtho for strabismus and hyperopia
• Audiology for non syndromic hearing loss

Question 6

What is the management for children with achondroplasia?

Answer 6

• Address common health problems - obesity, OSA, recurrent AOM, kyphoscoliosis, hydrocephalus
• Normal life span
• Growth hormone supplementation is ineffective
• Avoid contact sports, diving, gymnastics and exercise caution with intubation given atlantoaxial instability
• Monitor for hearing loss and middle ear problems
• VP shunt for hydrocephalus
• Causes of death: respiratory insufficiency from small thorax and neurologic deficit from cervicomedullary junction compression

Question 7

What is the imaging required in Tuberous sclerosis syndrome patients? What is the monitoring?

Answer 7

• Tests
  
  • TSC1 and 2 molecular genetic testing
• Imaging
  
  • Brain MRI
  • EEG
  • Echo
  • RBUS
• Consults - ophtho, neuro, genetics, neurosurg
• Treatment
  
  • mTOR inhibitor therapy for progressing SEGAs that may require neurosurg
  • Vigabatrin for seizures
  • Brain MRI q3 years for patients < 25 years to monitor for SEGAs
  • CT every 5-10 years in asymptomatic females > 18 to monitor for LAM
• Screening & surveillance when newly diagnosed
  
  • Genetics: 3 generation FHx, genetic counseling
  • CNS: brain MRI, counsel on infantile spasms, baseline EEG
  • Renal: MRI of abdomen, screen for HTN, renal function (eGFR)
  • Lung: baseline PFT (if old enough), imaging if symptomatic (typically adults)
  • Skin: regular skin exam
  • Heart: consider fetal echo, then obtain echo by 3yo, ECG in all ages
  • Eye: complete ophthalmic evaluation

Question 8

What is the recommended T21 screening?

Answer 8

• From birth - 1 mo
  
  • Screening echo
  • Feeding study if hypotonia, choking with feeds, FTT
  • Eye exam for cataracts
  • Hx/PE for duodenal atresia or anorectal atresia
  • CBC to R/O transient myeloproliferative disorder, polycythemia (1st week of life)
  • TSH (may be part of NBS)
  • If cardiac surgery or hypotonia: evaluate apnea, bradycardia, or oxygen desaturation with car seat prior to discharge
• 1mo-1y
  
  • Another eye exam for cataracts + strabismus, nystagmus
  • Audiology eval at 6mo
  • Assess for OSA sx
• 1y-5y
  
  • Sleep study by age 4yo
  • At 30mo, discuss transition to preschool & IEP
  • If chronic cardiac or pulmonary disease: 23-valent pneumococcal vaccine at >2yo
  • Reassure regarding delayed and irregular dental eruption

Question 9

What associations with hemihypertrophy?

Answer 9

• Associated with several genetic syndromes, including:
  
  • Beckwith-Wiedman
  • Russel-Silver syndrome
  • PTEN hamartoma tumor syndrome
  • NF1
• Hemihypertrophy is associated with an increased risk for: embryonal tumors, in particular Wilms tumor and hepatoblastoma

Question 10

What is the recommended screening protocol for children at risk of Wilm’s tumours or hepatoblastoma?

Answer 10

• Refer to geneticist
• Abdominal ultrasound Q3mo until 7yo
• Serum AFP Q3mo until 4yo
• Daily caretaker abdominal examination at discretion of parent/caregiver

Question 11

What are the teratogenic effects of phenytoin, carbamazepine, and valproic acid?

Answer 11

• Carbamazepine
  
  • Spina bifida, possible neurodevelopmental delay
• Phenytoin
  
  • Congenital anomalies, IUGR, neuroblastoma, bleeding (vitamin K deficiency)
• Valproic acid
  
  • CNS (spina bifida), facial and cardiac anomalies, limb defects, impaired neurologic function, autism spectrum disorder

Question 12

What is the recommended management / surveillance for a patient with Marfan syndrome?

Answer 12

• Annual cardiac examination, including echocardiogram
• Annual ophthalmology examination
• Clinical examination for scoliosis, joint laxity, and pectus deformity every 6 months to 1 year

Question 13

What abnormalities are associated with a single umbilical artery?

Answer 13

T18 (most common), Diaphragmatic hernia, sirenomelia sequence, VACTERL, renal anomalies