Genetic Contributions to Stuttering Flashcards
4 Factors: The Importance of Genetic Knowledge
- Increase understanding of developmental process
- Influences successful speech, language & reading acquisition
- Early ID of children at risk
- “personalized medicine” targeting specific deficits
Genetics vs genomics
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
Nature vs. Nurture
All human traits have genetic and environmental components on a continuum
Myths
Genetic determinism (traits result from specific genes) No treatment for disorders w/ genetic components
Human genome
23 pairs of chromosomes
50% from each parent
Chromosome
Consists of tightly wound DNA & protein
Gene
- 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
Allele
Different versions of the same gene
Everyone has two alleles for each gene
Methods of genetic research
- Behavioural - frequency, aggregation/pedigree, occurrence
- Statistical - segregation, twin concordance
- Molecular - linkage, genome-wide association, next generation sequencing (whole genome or exome)
Genetic Mutations
- 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
Behavioural Genetics (Low standard) Proband
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
Family Pedigree
-illustration of who in family has disorder or trait
Mendelian Modes of Inheritance
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
Non-mendelian Inheritance
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
Statistical Evidence (Medium Standard)
Twin concordance
Heritability
Segregation
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
Molecular Genetic Evidence (High Standard)
Linkage
- 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)
Molecular Genetic Evidence (High Standard)
Genome wide association
- single nucleotide polymorphisms (SNPs)
- Contingent negative variations (CNVs)
- Required large numbers (1000s) of unrelated probands
- Only 1 study right now
Co-occurance w/ other disorders
=70% have oc-occuring artic, phono and/or language disorder
-may share same underlying genetic cause as stuttering
Co-occuring Disorders
Down Syndrom2 Tourette's Fragile X Prader-Willi NF1 Turner Syndrome
Is stuttering heritable? (4)
YES
- runs in families (79% may also have immediate family member)
- If one ID twin stutters, other does 23-63%. Fraternal - 3-19%. Identical twins 100% DNA, fraternal 50% DNA. Stuttering 70-80% heritable)
- few dozen chromosomes involved
- known genetic disorders associated w/ higher rates of disfluent speech
Questions regarding stuttering onset
When does it happen?
Who is affected?
How does it happen?
What happens?
When: Age at Onset
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
How: Manner of Onset
40% sudden (1-3 days), 33% intermediate (1-2 weeks), 28% gradual ( >2 weeks)
Disfluencies near onset (per 100 syllables)
Stuttering children: 10.37
Normal Children: 1.33
What: Secondary Xtics
52% of children have @ least 1:
- facial contortions
- eye closing
- head tilting
- respiratory irregularities
- others
What: Stuttering Severity at onset
Severity/Clinicians/Parents
Mild / 35% / 45%
Moderate / 45% / 27%
Severe / 20% / 28%
What: Reported Stress at Onset
Illness - 14% Emotional Upset - 40% Behavioural stress - 36% Rapid lang. development - 40% Word finding words - 43%
What: Children’s awareness & reactions assessed through:
- Parent reports
- Children’s response to clinician probing
- Puppet task (identification w/ fluent or non-fluent puppet - rise in awareness b/t 4 & 5)
Rates of Persistency/Natural Recovery**
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%
Persistence and Recovery : Gender
Gender / Persistent / Recovered
Male / 30% / 70%
Females / 18% / 82%
Ratio: 3.67 m/f / 1.89 m/f
Risk For Persistence: Primary Factors
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
Risk For Persistence: Lesser Factors
Secondary
- Severity
- Secondary xtics
- Phonology
- Expressive language
- Acoustic Features
Tertiary
- Concomitant disorders
- Awareness ; emotional reactions
