Screening for Genetic Etiologies of Developmental Disabilities

Question 1

Gross motor stages in babies

Answer 1

Month 2-4.5: Rolls over
Month 5-8: Sits without support
Month 10-14: Stands Alone
Month 14-20: Walks up Steps
Month 21-28: Pedals tricycle
Month 30-44: Balances on one foot
By Age 6: Rhythmic skipping
By age 10: Holds tandem stance for 10 sec (eyes closed)

Question 2

Fine motor stages in babies

Answer 2

Month 2.5-4: grasps rattle
Month 4.5-7: Transfers cube hand to hand
Month 8-12: Has neat pincer grasp
Month 15-20: Builds tower of four cubes
Month 18-24: Imitates vertical line
Month 28-36: Copies circle
By Age 5: Draws a square
By Age 7: Draws diagonal line
By age 12: Draws 3D cube

Question 3

APGAR

Answer 3

A - Appearance (color)
P - Pulse - (heart rate)
G - Grimace (reflex irritability)
A - Activity (muscle tone)
R - Respiration (respiratory effort)

Question 4

What is APGAR used for?

Answer 4

• Used to assess the condition and prognosis of a newborn
• Performed at 1 minute and 5 minutes of life
• Score of 7 or higher = good or excellent

Question 5

Evaluation of a child with global developmental delay

Answer 5

• SNP oligonucleotide array
• Fragile X molecular testing (2.6% yield)
• Exome testing
• Routine metabolic screen is not helpful if only mildly delayed
• Routine karyotype (no longer the first line of testing)

Question 6

Intellectual Disability (MR)

Answer 6

• Defined as an IQ less than 70
• Likely to be multifactorial in origin
• Approx. 75% of individuals with moderate to severe MR have an identifiable cause.

Question 7

Genetic evaluation of MR

Answer 7

• Similar to work up for child with GDD
• SNP Oligonucleotide array analysis
• Consider MRI if clinically indicated
• Single gene testing if a specific disorder is suspected
• Metabolic studies
• Exome testing
• Follow up is key!

Question 8

Autism heretibility

Answer 8

• 5-10% of autism is due to an identifiable disorder (chromosome abnormality, fragile X syndrome, oligonucleotide array abnormalities)
• Empiric recurrence risks available:
  Range from 3-10%
  Some suggest 25% risk may be given if there are 2 or more affect siblings (suggesting an underlying genetic syndrome yet to be characterized)
• Twin Studies: 90% concordance of ASD, 70% concordance of autism
• Copy Number Variation found on oligonucleotide array analysis (7-10% of individuals with ASD)

Question 9

Genetic Testing for Autism

Answer 9

• SNP oligonucleotide array testing
• Molecular Fragile X Studies
• Metabolic testing (limited use)
• Exome slice testing
• Exome testing

Question 10

Advantages of SNP Array

Answer 10

• Detects chromosome imbalances that may not be detected by traditional karyotyping
• Identifies and further characterizes chromosomes imbalances identified by karyotyping (unbalanced rearrangements, etc.)
• adding the SNP array identifies regions of homozygosity (ROS)

Question 11

Limitations of Array CHG

Answer 11

• Cannot find BALANCED chromosome rearrangements (translocations, insertions, inversions)
• Cannot detect change in gene DNA sequences
• Cannot detect gains or losses in regions of the genome not covered by the array)
• Does not rule out most of the known genetic syndromes
• cannot detect low level mosaicism (<20-25%)
• Can detect DNA dosage gains or losses of unclear/uncertain clinical significance

Question 12

All kids with developmental disabilities should have

Answer 12

SNP oligonucleotide array analysis

Molecular Fragile X testing