CD: DS and FX Flashcards
What is DS? (2)
- Chromosomal disorder caused by an extra chromosome 21
2. Results in intellectual disability and physical abnormalities
What is the incidence of DS?
1/700 live births
What is the link between maternal age and DS? (4)
- Majority are born to women over 35 years (80%)
- 20 years: 1/2000
- 35: 1/365
- 40: 1/100
What is the aetiology of DS?
- 95% = extra chromosome (47), typically maternally derived
2. 5% = typical 46 chromosomes but extra chromosome 21 translocated to another chromosome
What is the most common translocation in DS?
t(14;21), then (21;22)
Summarise the impact of DS (5)
- Characteristic phenotype
- Delayed growth and development
- Intellectual disability
- Cardiac manifestations (50%)
- Gastro-intestinal manifestations (5%)
Describe the characteristics of a newborn with DS (2)
- Placid, rarely cry
2. Hypotonia
Describe the physical appearance of DS (7)
- Flat facial profile
- Small head and face
- Sometimes tongue is large
- Extra skin around back of the neck
- Ears are small, rounded and low-set
- Hands = short and broad, single palm cream
- Short in height
Describe the growth and development in DS (3)
- Mean IQ = 50 (average 100)
- Delay of physical and intellectual development
- Increased incidence of autism and ADHD
How is DS diagnosed before birth? (3)
- Ultrasonography
- Blood tests of mother
- Diagnosis confirmed via chorionic villus sampling, amniocentesis with karotype analysis or chromosomal microarray analysis
How is DS diagnosed after birth? (3)
- Appearance
- Blood tests
- Karotyping
What is the intervention for DS? (3)
- Regular monitoring: ECG, thyroid screening, hearing evaluations, opthalmology, growth, obstructive sleep apnea
- Treatment of specific symptoms
- Genetic counselling
What is the prognosis of DS? (3)
- Better compared to other extra chromosomal disorders eg. Trisomy 18
- Ageing process accelerated
- Most survive to adulthood
- Increased risk of Alzheimer’s
What is the average life expectancy in DS?
55 years but some live until 70/80s
What reduces the life expectancy in DS? (3)
- Heart disease
- Increased susceptibility to infections
- Leukaemia
Give 2 examples of specific symptoms treated in DS
- Congenital cardiac anomalies are repaired surgically
2. Hypothyroidism is treated with thyroid hormone support
What is Fragile X?
- Genetic abnormality on the X chromosome
2. Leads to intellectual disability and behavioural disorders
What is the prevalence of fragile X?
- Boys (1/4000) girls (1/8000)
- Girls typically less impaired
- Most commonly diagnosed inherited caused of intellectual disability
Summarise the inheritance pattern of fragile X (3)
- X-linked dominant pattern
- Males: mutation in the only copy of a gene in each cell causes the disorder
- Females: mutation in one of the two copies causes the disorder
What is a premutation that women can have? (3)
- FMRI gene premutation on the X chromosome can expand to more than 200 CGG repeats in cells that develop into eggs
- Increased risk of having a child with fragile X syndrome
- Men pass premutation only to daughters, sons receive a Y chromosome which does not contain FMR1 gene
What is the aetiology of Fragile X? (2)
- Abnormality of FMR1 gene on the X chromsome
- People with 55 to 200 extra copies are considered to have a premutation (don’t have disorder but offspring have greater risk)
Summarise the characteristics of Fragile X (5)
- Physical features
- Intellectual disability
- Hyper-extensible joints
- Heart disease
- Premature ovarian failure (women with premature ovarian failure, menopause in mid 30s)
What are the physical features of Fragile X? (4)
- Large, protuberant ears
- Prominent chin and forehead
- High arched palate
- Macroorchidism (abnormally large testes in post-pubertal male)
What are the cognitive abnormalities which may occur in Fragile X? (2)
- Mild-moderate intellectual disability
2. ASD features
How is Fragile X diagnosed? (3)
- DNA testing
- Frequently not suspected until adolescence (depending on symptom severity)
- Boys with ASD and intellectual disability should be tested for Fragile X
How is Fragile X treated?
- SLTs, OTs
2. Medication: stimulants, anti-depressants, anti-anxiety
