Chromosomal Syndromes Flashcards
Define Down’s Syndrome.
Trisomy 21
Define Edward’s Syndrome.
Trisomy 18
Define Patau Syndrome.
Trisomy 13
Define Noonan Syndrome.
Autosomal dominant
Defect in a gene on chromosome 12
De novo mutations are possible.
Define Turner Syndrome.
45, XO
Genetic defect, in females, resulting from the complete or partial absence of an X chromosome
Define Klinefelter Syndrome.
47, XXY
Genetic defect of the sex chromosomes in males
Define Prader-Willi Syndrome.
Imprinting disorder affecting the paternal copy of chromosome 15.
(Paternal Prader-Willi)
Define Angelman syndrome
Imprinting disorder affecting the maternal copy of chr15
Define Fragile X
X-linked dominant disease caused by a CGG trinucleotide repeat expansion in FMR1 gene
Define William’s syndrome
multisystem developmental disorder caused by a deletion at chromosome 7
Which chromosome is affected in Cri du Chat?
Chromosome 5
What combined test results are indicative of Down’s Syndrome?
↑ HCG
↓ PAPP-A
Thickened nuchal translucency
What quadruple test results are indicative of Down’s Syndrome?
↑ HCG
↑ Inhibin A
↓ AFP (alpha-fetoprotein)
↓ Unconjugated Oestriol
Give 7 facial features in Down syndrome
Upslanting palpebral fissures
Epicanthic folds
Brushfield spots in iris
Protruding tongue
Small low-set ears
Round/ flat face
What is 5 clinical features is Down’s Syndrome associated with?
Single palmar crease, pronounced ‘sandal gap’ between big + first toe
Hypotonia
Congenital heart defects (40-50%)
Duodenal atresia
Hirschsprung’s disease
What cardiac complication is most common in Down’s syndrome?
AVSD (endocardial cushion defect) 40%
VSD (30%)
Give 9 conditions commonly seen in Down syndrome
Learning difficulties
Short stature
Atlantoaxial instability
Chronic secretory otitis media- conductive hearing loss.
Recurrent respiratory infections
Hypothyroidism
ALL
Alzheimers
Subfertility
Summarise the epidemiology of Down’s Syndrome.
1/700 live births.
Most common genetic cause of learning difficulties.
2nd affected child is 1/200 if >35 + double the age-specific rate if <35.
Summarise the epidemiology of Edward’s Syndrome.
1 in 5000 live births.
Summarise the epidemiology of Patau Syndrome.
1 in 15,000 live births.
Summarise the epidemiology of Turner Syndrome.
1/2500 females.
No race/ethnic trends.
Summarise the epidemiology of Klinefelter Syndrome.
1/1000 males.
Summarise the epidemiology of Prader-Willi Syndrome.
1 in 25,000 newborns.
What are 6 presenting features of Turner Syndrome?
CHD: Bicuspid aortic valve (15%), Coarctation of aorta (5-10%)
Cystic hygroma
Horseshoe kidneys (40%)
Hypothyroidism
Primary amenorrhoea, ovarian failure + infertility (high gonadotrophins)
Failure of breast development, although normal pubic hair development.
What are 7 physical signs of Turner Syndrome?
- Neonatal lymphoedema of the hands, feet + cutis laxa (loose folds of skin, esp. at the neck)
- Short stature
- Webbed neck
- Wide carrying angle (cubitus valgus)
- Broad chest with widely spaced nipples (shield chest)
- Multiple pigmented naevi
- Short fourth metacarpal
Which autoimmune/ auto inflammatory diseases are more common in Turners?
AI Thyroiditis
Crohns
What may be diagnosed pre-natally in Turners syndrome?
Cystic hygroma
What are 6 signs and symptoms of Klinefelter Syndrome?
Tall stature
Hypogonadism: lack of secondary sexual characteristics
High gonadotrophin levels but low testosterone
Small, firm testes
Infertile
Gynaecomastia: increased incidence of breast cancer
What are 5 signs and symptoms of Patau Syndrome?
Microcephalic
Small eyes
Cleft lip/palate
Polydactyly
Scalp lesions
What are 4 signs and symptoms of Edward’s Syndrome?
Micrognathia
Low-set ears
Rocker bottom feet
Overlapping of fingers
What are 5 signs and symptoms of Fragile X syndrome?
Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism
What are 4 signs and symptoms of Noonan syndrome?
Webbed neck
Pectus excavatum
Short stature
Cardiac: Pulmonary valve stenosis
Describe the intellectual development in Noonan syndrome
Delayed intellectual development
Normal by adulthood in 2/3
What haematological problem may be seen in Noonan syndrome?
Factor XI deficiency
What are 3 signs and symptoms of Pierre Robin Syndrome?
Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate
What are 3 signs and symptoms of Prader-Willi syndrome?
Hypotonia
Hypogonadism
Obesity
What are 5 signs and symptoms of William’s Syndrome?
Short stature
Learning difficulties
Friendly, extrovert personality
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis
Give 5 signs/ symptoms of Cri-du-chat syndrome
Characteristic cry due to larynx + neurological problems
Feeding difficulties + poor weight gain
Learning difficulties
Microcephaly + micrognathism
Hypertelorism
What investigation should be performed for general chromosomal syndromes?
Karyotyping
When is the combined screening test performed? When is the quadruple test performed?
Combined: 11-13+6w
Quad: 15-20w
What combined test results are indicative of Patau syndrome?
↓ HCG
↓ PAPP-A
Thickened nuchal translucency
What combined test results are indicative of Edward’s syndrome?
↓ HCG
↓ PAPP-A
Thickened nuchal translucency
What quadruple test results are indicative of Edward’s syndrome?
↓ AFP
↓ Unconjugated Oestriol
↓ HCG
Normal Inhibin A
What quadruple test results are indicative of Neural Tube defects?
↑ AFP
Normal Unconjugated Oestriol
Normal HCG
Normal Inhibin A
What do the combined and quadruple screening tests provide?
Return either a ‘lower chance’ or ‘higher chance’ result
‘lower chance’: 1 in 150 chance or more e.g. 1 in 300
‘higher chance’: 1 in 150 chance or less e.g. 1 in 100
If a women has a higher chance result from initial screening, what occurs?
Offered 2nd screening test (NIPT) or a diagnostic test (e.g. amniocentesis or chorionic villus sampling (CVS).
What does NIPT analyse?
Non-invasive pre-natal screening test
analyses small DNA fragments that circulate in the blood of a pregnant woman (cell free fetal DNA, cffDNA)
cffDNA is derived from placental cells + is usually identical to fetal DNA
When can diagnostic tests of chromosomal syndromes be performed?
Chorionic villus sampling: 11-14w. Tests placental tissue. Transabdominal or Transcervical.
Amniocentesis: 15-20w. Tests amniotic fluid. Transabdominal.
What tests should be performed in a child with Down’s Syndrome?
Screening for complications: Echocardiography, TFTs, hearing + vision tests.
How do Noonan and Turners syndrome differ?
Noonan: Effects M + F
Turners: F
What investigations should be performed for Noonan Syndrome?
Molecular genetic test: Ras/MAPK pathway mutations e.g. PTPN11
FBC + Coagulation screen
ECG + Echo
Renal USS
Karyotype = NORMAL
What investigations should be performed for Turner Syndrome?
Chromosomal studies: Karotype confirmation
Bloods:
U+Es
TFTs
Increased LH + FSH confirm ovarian failure.
Renal USS
ECG + Echo
What is the management for Down’s Syndrome?
Multidisciplinary approach: Parental education + support, genetic counselling, IQ testing with appropriate educational input, regular follow-up.
Medical: Abx in recurrent resp. infections, thyroid hormone for hypothyroidism.
Surgical: Congenital heart defects, oesophageal/ duodenal atresia.
What is the management for Edward’s Syndrome?
MDT approach:
OT + PT.
NG tube.
Nursing care.
Counselling + parent support.
What is the management for Patau Syndrome?
Palliative care as most babies will die within 1st few days.
Counselling and support.
What is the management for Noonan Syndrome?
Correction of congenital heart defects.
Recombinant growth hormone.
Refer to urology for cryptorchidism.
What is the management for Turner Syndrome?
Surgical tx: Congenital heart defect correction, grommets (significant secretory otitis media), plastic surgery (neck webbing), remove of gonads if present (50% malignant change).
Hormonal tx:
- Growth hormone therapy.
- Oestrogen replacement therapy (12–15 years)
What is the management for Klinefelter Syndrome?
Conservative: SALT, educational + behavioural therapy, OT, PT + psychological therapy.
Medical: Fertility tx, testosterone replacement or ICSI.
Surgery: Breast reduction surgery.
What is the management for Prader-Willi syndrome?
Weight management: Refer to obesity
Cryptorchidism: Surgery
Hormone treatments: GH supplements.
Psychological: CBT, SSRIs
What are the complications for Down’s syndrome?
Decreased fertility.
Increased risk of leukaemia; transient myeloproliferative disorder + AML (mutations in the haematopoietic transcription factor gene, GATA1).
Increased incidence of Alzheimer’s disease by 40 years (amyloid protein coding gene located on chromosome 21).
What are the complications for Edward’s Syndrome?
Cardiac abnormalities
Feeding difficulties
Aspiration pneumonia
What are the complications for Patau Syndrome?
Kidney defects
Spinal defects
Infections
Intellectual disability + motor disorder
What are the complications for Noonan Syndrome?
Cardiac abnormalities
What are the complications for Turner Syndrome?
Infertility
Shorter stature
Psychological effects
What are the complications for Klinefelter’s Syndrome?
Increased risk T2DM
Cardiovascular disease
Hypothyroidism
Anxiety
Male breast cancer
What are the complications for Prader-Willi Syndrome?
Obesity
Type 2 Diabetes Mellitus
Metabolic syndrome
Psychosis
What is the prognosis for Down’s Syndrome?
Antenatal: 75% of trisomy 21 spontaneously abort.
Childhood: 15–20% of Down syndrome children die <5 years, usually due to severe Congenital heart disease.
Adulthood: 50% survive >50 years but undergo premature ageing.
What is the prognosis of Edward’s Syndrome?
12% of infants survive longer than a year.
What is the prognosis for Patau Syndrome?
More than 80% die within 1st year of life.
What is the prognosis for Noonan Syndrome?
Will require several medical interventions – may die of cardiology complication.
What is the prognosis for Turner Syndrome?
Can live a normal + healthy life.
Life expectancy is reduced.
What is the prognosis for Klinefelter Syndrome?
Can live a normal + healthy life.
Previously associated with prison life.
What is prognosis for Prader-Willi syndrome?
Shortened life expectancy due to complications of morbid obesity + increased pain threshold.
