How many births are affected with congenital malformations?
2-3%
Congential malformations are more likely to be genetic if…?
- multiple malformations
- dysmorphic
- family history of similar problems
Single malformations are often what?
Isolated events
What does diagnosis guide?
- prognosis
- management
- recurrence risk
What is the old-fashioned name for 22q11.2 deletion syndrome?
DiGeorge syndrome
What are the symptoms of 22q11.2 deletion syndrome?
- learning difficulties (50%)
- cleft palate (15%)
- velopharyngeal insufficiency
- congenital heart defects (75%)
- hypocalcaemia
- seizures
- immune deficiency
- renal malformation
- thin nose without flares and narrow mouth
How common is 22q11.2 deletion syndrome?
Around 1 in 5,000
How common is achondroplasia?
Around 1 in 20,000
What type of genetic disorder is achondroplasia?
Autosomal dominant - often a new mutation
The risk of achondroplasia increases with what?
Paternal age
What are the features of achondroplasia?
- rhizomelic limb shortening
- short stature
- foramen magnum compression/hydrocephalus
- big head compared to body
- arms reach waist level
Rhizomelic dwarfism is a feature of achondroplasia. What does it mean?
Rhizomelic dwarfism is a type of dwarfism where the dominant feature is proximal (i.e. femoral, humeral) limb shortening
How common is Beckwith-Wiedemann syndrome?
Around 1 in 10,000
What are the features of Beckwith-Wiedemann syndrome?
- large tongue
- ear pits/creases
- exomphalos
- hemihypertrophy
- neonatal hypoglycaemia
- increased risk of Wilms tumour (nephroblastoma)
Exomphalos is a feature of Beckwith-Wiedemann syndrome. What is exomphalos?
Weakness of the abdominal wall where the umbilical cord joins it. Allows the abdominal contents, mainly the bowel and the liver to protrude outside the abdominal cavity where they are contained in a loose sac that surrounds the umbilical cord
Hemihypertrophy is a feature of Beckwith-Wiedemann syndrome. What is hemihypertrophy?
A condition in which one side of the body or a part of one side of the body is larger than the other to an extent considered greater than the normal variation
What is the component chromosomal disorder?
Down syndrome
How common is Down syndrome?
Around 1 in 800 live births
What are the features of Down syndrome?
- learning disabilities
- congenital heart defects
- hypotonia in neonates
- single palmar crease
- cataracts
- hearing impairment
- hypothyroidism
- leukaemia
- atlanto-axial instability
- alzheimer’s disease
Why do those with Down syndrome get Alzheimer’s in their 40s or 50s?
The amyloid precursor protein is sat on chromosome 21, those with Down syndrome have 3 copies of it
Hypotonia is a feature of Down syndrome in neonates. What is hypotonia?
Hypotonia, also known as floppy baby syndrome, is a state of low muscle tone often involving reduced muscle strength
Atlantoaxial instability is a feature of Down syndrome. What is it?
Excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bony or ligamentous abnormality. Neurologic symptoms can occur when the spinal cord or adjacent nerve roots are involved
What affects the recurrence risk of Down syndrome?
Whether the 3 copies of chromosome 21 are individual or stuck to one another
In Down syndrome, if the extra copy of chromosome 21 is stuck to another, what does this mean in terms of recurrence risk?
Significant recurrence risk
Likely that one of the parents has a balanced translocation
If the 2 stuck together came from parent = 100% recurrence risk
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(1) Introduction to genetics25
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(2) Categories and impact of genetic disease79
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(3) Molecular genetic techniques0
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(4) Multifactorial disorders56
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(5) Familial cancer syndromes70
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(6) Chromosomal basis of inheritance0
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(7+8) Molecular basis of inherited disease0
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(9) Dysmorphology46
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(10+11) Techniques of chromosomal analysis0
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(12) Bioinformatics0
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(13) From gene to function to clinic0
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(14) Genomic imprinting0
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(15) Pharmacogenetics43
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(16+17) Huntington's Disease37
