Down's Syndrome & Turner Syndrome Flashcards
What is Down’s syndrome caused by?
3 copies of chromsome 21 (trisomy 21)
What are the characteristic features of Down’s syndrome?
Face:
- upslanting palpebral fissures
- prominent epicanthic folds
- Brushfield spots in iris
- protruding tongue
- small low-set ears
- round/flat face
Flat occiput
Single palmar crease
Hypotonia (reduced muscle tone)
Congenital heart defects
Duodenal atresia
Hirschsprung’s disease
What are epicanthic folds?
Folds of skin covering the medial portion of the eye and eyelid.
What are the palpebral fissures?
Gaps between the lower and upper eyelid.
What is the key risk factor for Down’s syndrome?
Increasing maternal age
What is risk of Down’s syndrome in maternal age of ≥45 y/o?
1 in 50 or greater
What is risk of Down’s syndrome in maternal age of 20 y/o?
1 in 1500
What 3 mutations can cause Down’s syndrome?
1) Nondisjunction (94%)
2) Robertsonian translocation (5%)
3) Mosaicism (1%)
What is nondisjunction?
The failure of one or more pairs of homologous chromosomes or sister chromatids to separate normally during nuclear division, usually resulting in an abnormal distribution of chromosomes in the daughter nuclei.
What is Hirschsprung’s disease?
A birth defect in which some nerve cells are missing in the large intestine, so a child’s intestine can’t move stool and becomes blocked.
What cardiac complications may be associated with Down’s syndrome?
1) Endocardial cushion defect (AV septal canal defect)
2) VSD
3) Tetralogy of Fallot
4) Isolated patent ductus arteriosus
5) Secundum atrial septal defect
What is the most common cardiac complication of Down’s?
Endocardial cushion defect
How is fertility impacted in Down’s (in males vs females)?
Males - almost always infertile.
Females - usually subfertile, have an increased incidence of problems with pregnancy and labour.
Why are males almost always infertile in Down’s?
Due to impaired spermatogenesis
Give some later complications of Down’s
1) subfertility
2) learning difficulties
3) short stature
4) repeated respiratory infections (+hearing impairment from glue ear)
5) acute lymphoblastic leukaemia
6) hypothyroidism
7) Alzheimer’s disease
8) atlantoaxial instability
Individuals with Down’s syndrome are more likely to suffer from vision and hearing problems.
What is a very common condition resulting in hearing problems in people with Down’s?
Otitis media and glue ear
What are some visual complications seen in Down’s?
- refractive errors
- strabismus
- cataracts: congenital and acquired
- recurrent blepharitis
- glaucoma
What is the 1st line screening for Down’s?
When does this take place?
Combined test - done between 11 - 13+6 weeks
If women book later in pregnancy, what 2 tests may be offered for Down’s screening?
Triple or quadruple test
What does the combined screening test for Down’s test consist of?
1) Maternal hCG
2) Maternal PAPP-A (pregnancy associated plasma protein A)
3) Nuchal translucency measurement
What combined test results indicates greater risk of Down’s?
1) Nuchal translucency: nuchal thickness >6mm
2) beta-HCG: higher
3) PAPPA: lower
What does the triple test for Down’s consist of?
1) b-HCG
2) Alpha-fetoprotein (AFP)
3) Serum oestriol
What triple test results indicates greater risk of Down’s?
1) b-HCG: higher
2) AFP: lower
3) Serum oestriol: lower
When can the triple & quadruple tests be performed?
14-20 weeks gestation
What does the quadruple test for Down’s consist of?
1) b-HCG
2) AFP
3) serum oestriol
4) inhibin-A
What quadruple test results indicates greater risk of Down’s?
1) b-HCG: higher
2) AFP: lower
3) serum oestriol: lower
4) inhibin-A: higher
What inhibin-A result indicates higher risk of Down’s?
Higher
The screening tests provide a risk score for the fetus having Down’s syndrome.
When are women offered further tests?
If risk of Down’s is ≥1 in 150
What 3 further tests can be offered to women with high risk for Down’s?
1) Chorionic villus sampling (CVS)
2) Amniocentesis
3) Non-invasive prenatal testing (NIPT)
What does chorionic villus sampling involve?
US guided biopsy of PLACENTAL tissue.
What does amniocentesis involve?
US guided aspiration of AMNIOTIC FLUID.
When is CVS vs amniocentesis done in pregnancy?
CVS - earlier in pregnancy (<15 weeks)
Amniocentesis - later in pregnancy once there is enough amniotic fluid to make it safer to take a sample
What is non-invasive prenatal testing (NIPT)?
A relatively new test for detecting abnormalities in the fetus during pregnancy.
It involves a simple blood test from the mother.
These fragments can be analysed and detect conditions such as Down’s.
Examples of MDT involved in Down’s care:
Speech and language therapy
Physiotherapy
Dietician
Paediatrician
GP
Cardiologist for congenital heart disease
ENT specialist for ear problems
Charities such as the Down’s Syndrome Association
Social services for social care and benefits
What are some routine follow up investigations that are important for children with Down’s syndrome?
1) Regular thyroid checks (2 yearly)
2) Echocardiogram to diagnose cardiac defects
3) Regular audiometry for hearing impairment
4) Regular eye checks
Average life expectancy of Down’s?
Prognosis varies depending on the severity of the associate complications.
The average life expectancy is 60 years.
What is Turner’s syndrome?
When a female has a single X chromosome, making them 45,XO or 45,X.
Features of Turner syndrome?
- short stature
- webbed neck
- high arched palate
- downward sloping eyes with ptosis
- broad chest with widely spaced nipples
- cubitus valgus
- underdeveloped ovaries with reduced function (1ary amenorrhoea)
- late or incomplete puberty
- infertility (most cases)
- bicuspid aortic valve (15%), coarctation of the aorta (5-10%)
What are the 3 key classic physical features of Turner’s syndrome to look out for in exams?
1) short stature
2) webbed neck
3) widely spaced nipples
What is cubitus valgus?
Refers to an abnormal feature of the elbow.
When the arm is extended downwards with the palms facing forward, the angle of the forearm at the elbow is exaggerated, angled away from the body.
How can Turner syndrome affect puberty?
Can cause 1ary amenorrhoea –> gonadotrophin levels will be elevated but ovaries will be underdeveloped.
This can lead to late or incomplete puberty.
What conditions have an increased incidence in Turner’s syndrome?
Autoimmune conditions e.g. autoimmune thyroiditis and Crohn’s disease
What is the most common renal abnormality in Turner’s?
Horseshoe kidney
What is a horseshoe kidney?
When two kidneys are fused or joined together. They form a shape like a horseshoe.
What are some associated conditions with Turner’s syndrome?
- Recurrent otitis media
- Recurrent UTIs
- Coarctation of the aorta
- Hypothyroidism
- HTN
- Obesity
- Diabetes
- Osteoporosis
- Various specific learning disabilities
There is no way to treat the underlying genetic cause of Turner syndrome.
What are 3 treatments that can be used to help with the symptoms?
1) GH therapy –> to prevent short stature
2) Oestrogen & progesterone replacement
3) Fertility treatment: can increase the chances of becoming pregnant
Role of oestrogen & progesterone replacement in Turner’s?
Can help establish female 2ary sex characteristics, regulate the menstrual cycle and prevent osteoporosis
