GDD/ID

Question 1

Name 6 first tier metabolic investigations for IDD/GDD/ASD if red flags (CCMG 2022-2023)

Answer 1

If regression:
Ammonia, blood gase, lactate +/- lytes, AG (if seizures, LOC)
Plasma amino acids
Urine organic acids +/- mucopolysaccharides (if HSM, course facial feature)
Very long chain fatty acids
Total plasma homocysteine

Creatine panel (if hypotonia, movement disorders or seizures)
Copper, ceruloplasmin (if movement disorders)

CCMG - based on clinical presentation

Question 2

What is the genetic test and indication for Rett Syndrome?

Answer 2

MECP2 testing
Mod-severe ID, clinical features (hand wringing, developmental regression and plateau consistent with Rett syndrome)

Question 3

Name 2 additional genetic test to Fragile X and microarray for ID/GDD and their indication

Answer 3

MECP2 testing – moderate to severe ID, clinical features of Rett (hand wringing, developmental regression and plateau consistent with Rett syndrome)

Whole exome sequencing – if moderate to severe ID, syndromic features, negative first line testing

PTEN – macrocephaly if >98%ile, >2.5 SD

Karyotype – short stature, dysmorphic features

Question 4

Diagnostic criteria for GDD

Answer 4

• Delays >2 developmental domains (speech/language, social/personal, gross or fine motor, cognition, activities of daily living)  standard deviations below the mean with standardized tests
• Children <5 yo

Question 5

Diagnostic criteria for IDD

Answer 5

o Cognitive impairment in both clinical and standardized testing (FSIQ <70 +/-5)
o Deficit in adaptive functioning (limits in one or more activities of daily life: communication, social participation, independent living, across multiple environments) to the extend sufficient for ongoing support
o Onset in developmental period

Question 6

Diagnostic yield of microarray in IDD/GDD?

Answer 6

8-20% by CPS
12-19% in mild, 20-30% in severe ID CCMG

Question 7

List 6 benefits of identifying aetiology in GDD by microarray/CMA?

Answer 7

o Timely initiation of causal treatment or supportive management
o Prevention of complications
o Improved prognostication
o Accurate genetic counselling regarding recurrence risk, and prenatal/preimplantation genetic diagnosis when indicated
o Better access to services in the community
o Resolution of a diagnostic odyssey or avoidance of inappropriate, costly, and traumatizing tests

Question 8

List 6 indications for MRI in IDD?

Answer 8

• Micro/macrocephaly
• Abnormal neurological exam (pyramidal/extra-pyramidal symptoms): Focal findings/ asymmetry, Abnormal tone, Abnormal movements (dystonia, chorea, athetosis, ataxia, rigidity…), Abnormal eye movements, Abnormal fundi
• Developmental regression
• Seizures
• Altered LOC

Question 9

3 next steps in GDD/ID if microarray has non-specific findings or normal?

Answer 9

1. Complete Tier 1 testing, consider Tier 2 testing
2. Genetics referral
3. Follow

• MRI
• Genetics referral for exome sequencing
• Family testing if VUS

Question 10

Level of functioning/prognosis by severity of IDD?

Answer 10

Question 11

Name 5 differences between GDD and ASD in early development

Answer 11

Question 12

Name 3 single gene disorders associated with IDD ?

Answer 12

Fragile X (FMR1 gene with repeats), Rett syndrome (MECP2), Tuberous sclerosis (TSC1/2)

Question 13

name 5 X-linked IDD syndromes

Answer 13

Fragile X
X linked adrenoleukodystrophy
Rett syndrome
MECP2 duplication syndrome
Lesch-Nyhan syndrome
Duchenne muscular dystrophy
OTC deficiency
Menkes disease
Alpha-thalassemia ID
Incontinentia pigmenti
Dyskeratosis congenita
Cornelia de lange – x linked dominant

Question 14

Name 5 treatable IEM that cause GDD

Answer 14

Maple syrup urine disease
PKU
Homocysteinuria
Galactosemia
Biotinidase deficiency
Glutaric acidemia
Isovaleric acemia
Methymalonic acidemia
Citrin deficiency
Glutamine synthetase deficiency
OTC deficiency
X-linked adrenoleukodystrophy

Question 15

Name 5 neurological features of IEM

Answer 15

• Micro/macrocephaly
• Hypotonia
• Movement disorder – ie dystonia
• Facial dysmorphisms
• Sensory deficits – ie cataracts, retinopathy
• Absent or brisk reflexes
• Positive Babinski
• Abnormal gait or inability to walk at developmental age
• Cataracts
• Abnormal smell

Question 16

Name 5 non-neurological organ systems involved in IEM and the associated red flags

Answer 16

Body systems
- Hepatic
- Renal
- Pulmonary
- Cardiac
- Endocrine
- Visual
- Auditory
- Cutaneous
- Brain
- GI
- Reproductive

Question 17

3 possible trajectories in GDD?

Answer 17

o Ongoing developmental progress reaching average cognitive functioning
o Impaired developmental progress leading to intellectual disability or specific learning disorder
o Regression

Question 18

2 contraversies in the use of GDD

Answer 18

Delay implies ability to catch up whereas some children may be impaired and unable to catch up

Wide range of delays limited uniformity within the diagnosis - highly variable treatments

Question 19

what is the diagnostic yield of metabolic testing in GDD/ID?

Answer 19

1-5% (CPS)
0.25-0.42% (CCMG)

Question 20

What is the CMAJ opinion on screening for developmental delay ?

Answer 20

Does NOT improves health outcomes
Does NOT identify otherwise unrecognized cases
High FALSE POSITIVE rate
Minimal evidence for early intervention in developmental delays

Developmental surveillance (ongoing monitoring - identification of risk factors and elicitation of parental concerns) is recommended

Question 21

Clinical features of Fragile X

Answer 21

Question 22

Name 3 major groups of IEM and the associated clinical features & recommended investigations

Answer 22

Question 23

Which diagnosis are specifically associated with SLD in mathematics?

Answer 23

Question 24

4 things that you have to rule out to make a diagnosis of specific learning disorder.

Answer 24

Intellectual disability
visual impairment
auditory impairment
neurological disorder
mental disorder
psychosocial adversity
inadequate instruction

Question 25

Give two examples of aided, low-tech assisted and augmentative communication devices

Answer 25

“no tech”
motor behaviors, gestures, vocalizations, verbalizations (or verbal approximations), proxemics (approach or avoidance of a communication partner), eye gaze, and facial expressions, sign language

“low tech aided”
picture or object communication, the Picture Exchange Communication System (PECS), partner assisted scanning (e.g partner lists options)
“light Tech aided”: voice output communication systems which are typically battery operated and have a static (non-changing) display
Big Mac, Rocker Plate Talker, Step by Step, Cheaptalk, Tech Talk, Go Talk, Supertalker, or 7-Level Communication Builder.

“High Tech aided”: Systems typically requiring an electronic power source and having a dynamic (changing—i.e., computerized LCD screen) display
DynaVox Maestro, a Prentke Romich Accent, a Saltillo Nova-Chat or an iPad

Question 26

Name 5 things parents should know about his long-term outcomes for learning and independence. for mild IDD

Answer 26

Likely to live independently
· Support required with complex tasks like financial management
· Competitive, semi-skilled job without direct supervision
· Able to read (education level up to ~ grade 6)
· Ongoing difficulties with memory, abstract thinking, executive functioning

Question 27

Family that are refugees, 4yo child referred for developmental delay, but they don’t see anything wrong, list 6 reasons why families new to Canada may not report developmental concerns (6 Reasons why newcomer would not seek advice re: child with GDD)

Answer 27

lack awareness of typical child development.
not know about resources and systems to help children with developmental problems.
not know that governments and schools provide supports and accommodations for people with disabilities.
be reluctant to identify concerns, for fear of affecting their success in applying for permanent status.
may face challenges that make it difficult to act on the health care provider’s advice, such as lack of support systems, grief at what they have sacrificed, shame about their child’s disability

Question 28

What is the definition of GDD by the DSM-V

Answer 28