3 - Genetics Flashcards
What is the extra chromosome in Patau’s and Edward’s?
Puberty, Education, Degree
Patau: Trisomy 13
Edward’s: Trisomy 18
Down’s: Trisomy 20+1
(Patau and Edward both have “rockerbottom feet”)
What is predictive testing?
Testing for a mutation of a gene that predicts a disease e.g BRCA1
What processes need to be done before genetic testing?
- Consent
- Genetic counselling
What is Karyotyping?
Looking at the number of chromosomes, their shape and their size
Can diagnosis Downs and Turner’s
What are some other types of genetic testing apart from karyotyping and predictive testing?
- Microarray testing
- Specific gene testing
- DNA sequencing
What are the dysmorphic features found in Down’s syndrome?
- Hypotonia
- Brachycephaly (small head with a flat back)
- Short neck
- Short stature
- Flattened face and nose
- Prominent epicanthic folds
- Upward sloping palpable fissures
- Single palmar crease
What are some co-morbidities associated with Downs Syndrome?
- Learning disability
- Recurrent otitis media
- Deafness and Glue ear
- Visual problems e.g myopia , strabismus and cataracts
- Hypothyroidism occurs in 10 – 20%
- ASD, VSD, PDA and tetralogy of Fallot (affects 1 in 3)
- Type 1 diabetes
- Obstructive sleep apnea
- Duodenal atresia
- Coaeliac disease
- Imperforate anus
- Acute Myeloid Leukaemia
- Dementia
What are the three antenatal screening tests for Downs syndrome?
- Combined
- Triple
- Quadruple
What is the combined test?
- First line
- Most accurate
- 11 to 14 weeks
- US NT>6mm and maternal blood tests (high b-hCG and low PAPPA)
What is the triple test?
- 14 to 20 weeks
- B-HCG: higher result indicates greater risk.
- Alpha-fetoprotein (AFP): lower result greater risk
- Serum oestriol: lower result greater risk
What is the quadruple test?
- 14 to 20 weeks gestation
- Identical to triple test but also includes maternal blood for inhibin-A. A higher inhibin-A indicates a greater risk
What is some diagnostic testing if there is a high risk of Downs on screening?
- Chorionic villus sampling (CVS): US guided biopsy of the placental tissue. Used before 15 weeks
- Amniocentesis: US guided aspiration of some amniotic fluid using a needle and syringe. This is later in pregnancy once there is enough amniotic fluid to make it safer to take a sample
- NIPT: maternal blood test, not diagnostic. Uses cell free DNA
What is the management when a baby is born with Downs syndrome?
Involve the multidisciplinary team
- OT
- Speech and language
- Physiotherapy
- Dietician
- Paediatrician
- GP
- Health visitors
- Cardiologist for congenital heart disease
- ENT
- Audiologists
- Optician for glasses
- Social services for social care and benefits
- Additional support with educational needs
- Charities such as the Down’s Syndrome Association
What routine checkups do children with Downs syndrome need?
- FBC
- Karyotyping
- Thyroid checks every 2 years
- Echocardiogram to diagnose cardiac defects
- Regular audiometry for hearing impairment
- Regular eye checks
What is the life expectancy for somebody with Downs syndrome?
60
Common causes of premature death: infections (e.g. pneumonia) cardiac disease (and CHD) and dementia
What is the aetiology and risk factors for Down syndrome?
Most common genetic cause of learning disability
Aetiology
Trisomy 21 (94-95%): Non disjunction during meiosis
Robertsonian translocation (3-4%): DS may be caused by translocation of the long arm of chromosome 21 to another chromosome, most commonly 14.
Trisomy 21 mosaicism (1-2%):
Risk
Maternal age
Previous child with DS
What is the most to least common cardiac complication with Down syndrome?
- Atrioventricular septal defect (45%)
- Ventricular septal defect (35%)
- Isolated secundum atrial septal defect (8%)
- Isolated persistent patent ductus arteriosus (7%)
- Isolated tetralogy of Fallot (4%)
- Other (1%)
What are some features of Edward’s syndrome and what is the prognosis?
Survive a few months maximum
- Low-set ears
- Micrognathia
- Microcephaly
- Overlapping 4th and 5th fingers
- Rocked bottomed feet
- Congenital heart disease
What are some features of Patau’s syndrome and what is the prognosis?
Survive a few weeks maximum
- Holoprosencephaly
- Cleft lip and palate
- Microcephaly
- Polydactyly
- Congenital heart disease
What is Klinefelter syndrome and some of the features of this?
A male with an additional X chromosome. XXY
Appear male until puberty when they get:
- Taller height
- Wider hips
- Gynaecomastia
- Weaker muscles
- Small testicles
- Reduced libido
- Shyness
- Infertility
- Subtle learning difficulties (particularly affecting speech and language)
How is Klinefelter’s managed?
- Testosterone injections improve many of the symptoms
- IVF for fertility
- Breast reduction surgery
Multidisciplinary team input:
- Speech and language therapy
- Occupational therapy
- Physiotherapy to strengthen muscles and joints
- Educational support
What is the prognosis with Klinefelter’s?
- Infertility (can have IVF)
- Osteoporosis
- Diabetes
- Anxiety and depression
- Breast cancer
Does Birun have Klinefelter’s?
No you f*cking idiot.
What is Turner’s syndrome and what are some of the features of this?
Female with single X chromosome (45XO)
- Short stature
- Webbed neck
- Broad chest with widely spaced nipples
- High arching palate
- Downward sloping eyes with ptosis
- Cubitus valgus
- Underdeveloped ovaries with reduced function
- Late or incomplete puberty
- Most women are infertile