Genetic Contributions to Stuttering

Question 1

4 Factors: The Importance of Genetic Knowledge

Answer 1

1. Increase understanding of developmental process
2. Influences successful speech, language & reading acquisition
3. Early ID of children at risk
4. “personalized medicine” targeting specific deficits

Question 2

Genetics vs genomics

Answer 2

Genetics - branch of science focusing on the means & consequences of biological inheritance
Genomics - study of whole genomes and how genes interact w/ each other and the environment

Question 3

Nature vs. Nurture

Answer 3

All human traits have genetic and environmental components on a continuum

Question 4

Myths

Answer 4

Genetic determinism (traits result from specific genes)
No treatment for disorders w/ genetic components

Question 5

Human genome

Answer 5

23 pairs of chromosomes

50% from each parent

Question 6

Chromosome

Answer 6

Consists of tightly wound DNA & protein

Question 7

Gene

Answer 7

• Found along length of chromosome
• Segment of DNA that contains instructions for making a specific protein required by the body
• Humans have 20,000-25,000 genes

Question 8

Allele

Answer 8

Different versions of the same gene

Everyone has two alleles for each gene

Question 9

Methods of genetic research

Answer 9

• Behavioural - frequency, aggregation/pedigree, occurrence
• Statistical - segregation, twin concordance
• Molecular - linkage, genome-wide association, next generation sequencing (whole genome or exome)

Question 10

Genetic Mutations

Answer 10

• Change in genetic code
• May be harmful, neutral or beneficial
• May be inherited from mother, father or both
• OR de novo mutation (appears for the first time in an individual)
• harmful genetic mutations change the DNA code such that the instructional message for protein production is also changed

Question 11

Behavioural Genetics (Low standard)
Proband

Answer 11

The person serving as the starting point for genetic study of a family
71% of affected probands have familiar stuttering
9% of control
=runs in families

Question 12

Family Pedigree

Answer 12

-illustration of who in family has disorder or trait

Question 13

Mendelian Modes of Inheritance

Answer 13

Autosomal Dominant
-One mutated gene that does not function properly is sufficient to cause the disorder

Autosomal Recessive
-Both mutated genes are required to cause the disorder

X-Linked

• Cause by mutations in the X chromosome
• Females (XX) w/ only 1 mutated chromosome have a working copy that can perform the needed cell functions
• Males (XY) with a mutation on the X chromosome are more severley affected b/c they lack a normal copy

Question 14

Non-mendelian Inheritance

Answer 14

Multifactoral inheritance

• No single gene causes a disorder
• Several genes interact w/ each other w/ the environment to produce disorder
  e. g. cleft lip & palate

Question 15

Statistical Evidence (Medium Standard)

Twin concordance
Heritability
Segregation

Answer 15

Monozygotic twins - 26-63%
Dizygotic twins - 3-19%

Large twin studies (33,000)
0.7-0.8

Several studies could not reach consensus on model

Question 16

Molecular Genetic Evidence (High Standard)

Linkage

Answer 16

• tendency of genes located closely together on a chromosome to both be inherited
• identify familial stuttering in closely related families (founder population, consanguineous) to increase likelihood of transmission
• Finding on several loci (inc chromosomes 1,3,5,7,9,12,13,15,18)

Question 17

Molecular Genetic Evidence (High Standard)

Genome wide association

Answer 17

• single nucleotide polymorphisms (SNPs)
• Contingent negative variations (CNVs)
• Required large numbers (1000s) of unrelated probands
• Only 1 study right now

Question 18

Co-occurance w/ other disorders

Answer 18

=70% have oc-occuring artic, phono and/or language disorder

-may share same underlying genetic cause as stuttering

Question 19

Co-occuring Disorders

Answer 19

Down Syndrom2
Tourette's
Fragile X
Prader-Willi
NF1
Turner Syndrome

Question 20

Is stuttering heritable? (4)

Answer 20

YES

1. runs in families (79% may also have immediate family member)
2. If one ID twin stutters, other does 23-63%. Fraternal - 3-19%. Identical twins 100% DNA, fraternal 50% DNA. Stuttering 70-80% heritable)
3. few dozen chromosomes involved
4. known genetic disorders associated w/ higher rates of disfluent speech

Question 21

Questions regarding stuttering onset

Answer 21

When does it happen?
Who is affected?
How does it happen?
What happens?

Question 22

When: Age at Onset

Answer 22

Range 16-60 months
Mean: 33.40 Months
(Boys: 33.60, girls: 32.95)

56% onsets b/t 24-36 months
84% from 18-42 months

Question 23

How: Manner of Onset

Answer 23

40% sudden (1-3 days), 33% intermediate (1-2 weeks), 28% gradual ( >2 weeks)

Question 24

Disfluencies near onset (per 100 syllables)

Answer 24

Stuttering children: 10.37

Normal Children: 1.33

Question 25

What: Secondary Xtics

Answer 25

52% of children have @ least 1: - facial contortions - eye closing - head tilting - respiratory irregularities - others

Question 26

What: Stuttering Severity at onset

Answer 26

Severity/Clinicians/Parents Mild / 35% / 45% Moderate / 45% / 27% Severe / 20% / 28%

Question 27

What: Reported Stress at Onset

Answer 27

``` Illness - 14% Emotional Upset - 40% Behavioural stress - 36% Rapid lang. development - 40% Word finding words - 43% ```

Question 28

What: Children's awareness & reactions assessed through:

Answer 28

- Parent reports - Children's response to clinician probing - Puppet task (identification w/ fluent or non-fluent puppet - rise in awareness b/t 4 & 5)

Question 29

Rates of Persistency/Natural Recovery****

Answer 29

Time Post Onset/ % Recovery this time / Remaining Chance of Recovery / % Chronic Stuttering 2 Years / 31% / 70% / 21% 3 Years / 63% / 16% / 21% 4 Years / 74% / 5% / 21% 5 Years / 79% / 0% / 21%

Question 30

Persistence and Recovery : Gender

Answer 30

Gender / Persistent / Recovered Male / 30% / 70% Females / 18% / 82% Ratio: 3.67 m/f / 1.89 m/f

Question 31

Risk For Persistence: Primary Factors

Answer 31

``` Family history (65% chance follow same trend as family history if persistency or recovery) Gender Stuttering Trends Duration of stuttering Age at onset Disfluency length Disfluency type; Prolongations/blocks ```

Question 32

Risk For Persistence: Lesser Factors

Answer 32

Secondary - Severity - Secondary xtics - Phonology - Expressive language - Acoustic Features Tertiary - Concomitant disorders - Awareness ; emotional reactions