CD: CDC and AS Flashcards
What is Cri-du-chat syndrome?
Chromsomal condition resulting from missing piece of chromosome 5
What is the prevalence of Cri-du-chat syndrome?
1 in 20,000 - 50,000 newborns
Summarise the aetiology of Cri-du-chat syndrome (3)
- Spontaneous deletion during embryo formation or development
- Deletion of the end of the short (p) arm of chromosome 5 (5p-)
- 10% inherit abnormality from unaffected parent
How does the aetiology vary in Cri-du-chat syndrome? (3)
- Symptoms are probably related to the loss of multiple genes on the short arm of chromosome 5
- Size of deletion varies between individuals
- Larger deletions = more severe intellectual disability and developmental delay
What gene is associated with severe intellectual disability?
CTNND2 loss
Explain the inheritance pattern of Cri-du-chat syndrome (3)
- Unaffected parent carries a chromosomal rearrangement called a balanced translocation
- Becomes unbalanced as passed to next generation
- Children are missing genetic material from the short arm of chromosome 5
Summarise the impact of Cri-du-chat syndrome (6)
- High pitched cry
- Intellectual disability
- Distinctive facial features
- Physical development
- Health difficulties
- Behavioural problems
What are 4 distinctive facial features of Cri-du-chat syndrome?
- Widely set eyes (hypertelorism)
- Low-set ears
- Small jaw
- Rounded face
What are 5 physical development characteristics in Cri-du-chat syndrome?
- Delayed development
- Small head size (microcephaly)
- Low birth weight
- Hypotonia in infancy
- Some born with heart defect
What is the variation in intellectual impairment in Cri-du-chat syndrome?
- Most have moderate-severe learning difficulty
2. Some will have mild
What are 7 associated health difficulties in Cri-du-chat syndrome?
- Scoliosis
- Constipation
- Reflux
- Respiratory tract infections
- Feeding difficulties
- Flat footedness
- Renal and heart problems
What are 3 behavioural problems found in Cri-du-chat syndrome?
- Hyperactivity
- Sleep difficulties
- ASD (30% meet cut off)
How is Cri-du-chat syndrome diagnosed?
- Evaluation of medical history and symptoms
2. Genetic testing
What is the prognosis of Cri-du-chat syndrome? (4)
- Most have normal life expectancy
- After 1st year = mortality and morbidity rates are low
- Serious organ defects may have worse prognosis
- Older children usually able to move, communicate verbally/sign and independent in self-care skills
What is the treatment of Cri-du-chat syndrome?
Early intervention in physio, SLT, behavioural modification and special education
What is Angelman syndrome?
- Complex genetic disorder that primarily affects the nervous system
- Causes severe physical and intellectual disability
What is the prevalence of Angelman syndrome?
1/12,000 - 20,000
Summarise the impacts of Angelman syndrome (6)
- Delayed development
- Intellectual disability
- Ataxia
- Seizures
- Happy, excitable personality
- Physical appearance
Describe the physical appearance of Angelman syndrome (4)
- “Coarse” facial description
- Unusually fair skin and light-coloured hair
- Small head size
- Crossed eyes (strabismus)
What are behavioural characteristics of Angelman syndrome? (5)
- Hyperactivity
- Short attention span
- Fascination with water
- Sleep difficulties
- Frequent laughing, smiling and hand-flapping
What is the “coarse” facial description of Angelman syndrome? (3)
- Lack usual fine and sharp facial appearance
- Rounded and heavy appearance with thickened skin
- Subcutaneous or bony tissues
Summarise the aetiology of Angelman syndrome (3)
- Spontaneous genetic changes during formation of reproductive cells or early embryonic development
- Unknown in 10-15%
- Small percentage: paternal uniparental disomy
What is parternal uniparent disomy in Angelman syndrome?
Inherits 2 copies of chromosome 15 from father rather than one from each parent
What causes light-coloured hair and fairskin in Angelman syndrome?
Loss of gene OCA2 located on chromosome 15
What mutations cause Angelman syndrome? (2)
- 70% due to deletion in maternal chromosome 15 containing UBE3A gene
- 11% caused by mutation in maternal copy of UBE3A gene
What is the inheritance pattern of Angelman syndrome?
- Rare that a genetic change is responsible
eg. mutation in the UBE3A gene or nearby region of DNA is passed to the next generation
How is Angelman syndrome diagnosed? (2)
- Physical exam of symptoms
2. Genetic testing
Give 4 types of genetic testing used to diagnosis Angelman syndrome
- Chromosome analysis eg. deletions
- Fluorescent in situ hybridisations eg. chromosome 15 deletions
- DNA methylation
- UBE3A gene mutation analysis
Summarise the treatment of Angelman syndrome (5)
- Anti-epileptic drugs
- Physiotherapy
- Back brace/spinal surgery to prevent worsening of scoliosis
- SLT
- Behavioural therapy
