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 condition on chromosome 12
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 leading to a karyotype of 47XXY (80–90% of cases) or more rarely a mosaic of 46XY/47XXY.
Define Prader-Willi Syndrome.
Imprinting disorder affecting the paternal copy of chromosome 15.
(Paternal Prader-Willi)
Explain the aetiology/risk factors for Down’s Syndrome.
- Non-disjunction at meiosis (95%): Extra maternal chromosome: karyotype 47XX þ 21 or 47XYþ21. Increased incidence of trisomy 21 secondary to non-dysjunction with increasing maternal age, especially >35 years and is independent of paternal age.
- Robertsonian translocation (4%): Chromosome 21 usually translocated onto chromosome 14.
- Mosaicism (1%): Some cells normal, some trisomy 21 due to non-dysjunction during mitosis after fertilization; usually less severely affected.
What is Down’s Syndrome associated with?
- Congenital heart disease (40%): AVSD, VSD, ASD, Fallot tetralogy, PDA.
- Gastrointestinal: Anal, oesophageal and duodenal atresia (one-third of infants with duodenal atresia are syndromic), Hirschsprung’s disease.
- Chronic secretory otitis media: Gives rise to conductive hearing loss.
- Others: Recurrent respiratory infections, cataracts, squints, hypothyroidism
Explain the aetiology/risk factors for Edward’s Syndrome and Patau Syndrome.
Similar to Down’s Syndrome
Explain the aetiology for Noonan Syndrome.
Autosomal dominant inheritance.
De novo mutations are possible.
Explain the aetiology of Turner Syndrome.
Classic TS: 45XO.
Mosaic TS: 45X0/46XX and rarely 45X0/46XY.
Two-thirds of classic TS lack paternal X chromosome. Not all the genes have been identified but loss of one copy of the SHOX gene leads to similar phenotype of short stature and skeletal abnormalities (Leri–Weill dyschondrosteosis).
Explain the aetiology of Klinefelter Syndrome.
Similar to Down’s syndrome.
Can rarely have 48 chromosomes (XXXY or XXYY). Most common reason is non-disjunction events.
Explain the aetiology of Prader-Willi Syndrome.
Deletion of the paternal copies on chromosome 15 which means there are no functional copies of the genes encoded. The mechanism of imprinting only occurs during the development of sperm.
Summarise the epidemiology of Down’s Syndrome.
1/700 live births. Most common genetic cause of learning difficulties. Second affected child is 1/200 if >35 and 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 Noonan Syndrome.
1 in 1000.
Most common genetic disorder associated with congenital heart disease.
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 the presenting signs and symptoms for Down’s Syndrome?
General: Neonatal hypotonia, short stature.
Developmental: Mild–moderate learning disability (IQ 25–70, with social skills exceeding other intellectual functions).
Craniofacial: Microcephaly, brachycephaly (shortness of skull), round face, epicanthic folds, upward sloping palpebral fissures, protruding tongue, flat nasal bridge, small ears, excess skin at back of neck, atlantoaxial instability.
Eyes: Strabismus, nystagmus, Brushfield spots in iris, cataracts.
Limbs: Fifth finger clinodactyly, single palmar crease, wide gap between first and second toes (saddle toes), hyperflexible joints in infants.
CVS: Murmurs dependent on congenital heart disease, arrhythmias, signs of heart failure.
GI: Constipation.
What are the presenting signs and symptoms of Turner Syndrome?
- Increased incidence of spontaneous abortions.
- Possible swollen hands and feet at birth.
- May present with signs of ovarian failure, amenorrhea, infertility.
- Failure of breast development) although there is normal pubic hair development.
- Short stature
Congenital malformations:
- Congenital heart defects (20%): Coarctation of the aorta (obstructed lymphatic system compression of developing aorta), hypoplastic left heart syndrome.
- Horseshoe kidneys (40%).
- Ovarian dysgenesis (95%).
What are physical signs of Turner Syndrome?
- Neonatal lymphoedema of the hands and feet and cutis laxa (loose folds of skin, especially at the neck)
- Neck webbing.
- Wide carrying angle (cubitus valgus)
- Broad chest with widely spaced nipples (shield chest)
- High pigmented naevi
- Hypoplastic nails
- Amblyopia
- Ptosis, strabismus.
- Short fourth metacarpal
What are signs and symptoms of Klinefelter Syndrome?
- Infertility
- Hypogonadism
- Gynecomastia in adolescence
- Tall stature
- May have learning difficulties or psychological problems
What are some signs and symptoms of Patau Syndrome?
Microcephalic, small eyes
Cleft lip/palate
Polydactyly
Scalp lesions
What are some signs and symptoms of Edward’s Syndrome?
Micrognathia
Low-set ears
Rocker bottom feet
Overlapping of fingers
What are some signs and symptoms of Fragile X syndrome?
Learning difficulties
Macrocephaly
Long face
Large ears
Macro-orchidism
What are some signs and symptoms of Noonan syndrome?
Webbed neck
Pectus excavatum
Short stature
Pulmonary stenosis
What are signs and symptoms of Pierre Robin Syndrome?
Micrognathia
Posterior displacement of the tongue (may result in upper airway obstruction)
Cleft palate
What are signs and symptoms of Prader-Willi syndrome?
Hypotonia
Hypogonadism
Obesity
What are some signs and symptoms of William’s Syndrome?
Short stature
Learning difficulties
Friendly, extrovert personality
Transient neonatal hypercalcaemia
Supravalvular aortic stenosis
What investigation should be performed for general chromosomal syndromes?
Karyotyping
What tests should be performed for Down’s Syndrome?
Antenatal screening: Maternal age combined with the triple test on maternal serum: AFP is decreaed, unconjugated oestriol is decreased and b-hCG is increased.
Confirmation of diagnosis: Prenatal examination of fetal cells from amniocentesis or chorionic villus sampling, postnatal chromosomal analysis.
Screening for complications: Echocardiography, TFTs, hearing and vision tests.
What investigations should be performed for Noonan Syndrome?
Bloods: FBC, coagulation profile.
Molecular genetic test: Ras/MAPK
ECG: Wide QRS, giant Q waves, left axis deviation.
Imaging:
- Echo: Congenital heart defects
- Abdominal ultrasound: Splenomegaly
- Renal ultrasound: Renal hypoplasia.
What investigations should be performed for Turner Syndrome?
Antenatal: Amniocentesis or chorionic villious sampling and karyotype analysis if diagnosis suspected (nuchal cystic hygroma/horseshoe kidney/left-sided cardiac anomalies, non-immune fetal hydrops).
Chromosomal studies: Karotype confirmation, confirmation of presence of possible Y chromosomal material (Y-centromeric probe). Differentiation from Noonan syndrome (phenotypically very similar).
Bloods: Increased LH and FSH confirm ovarian failure.
What is the management for Down’s Syndrome?
Multidisciplinary approach: Parental education and support, genetic counselling, IQ testing with appropriate educational input, regular follow-up.
Medical: Antibiotics in recurrent respiratory infections, thyroid hormone for hypothyroidism.
Surgical: Congenital heart defects, oesophageal/duodenal atresia.
What is the management for Edward’s Syndrome?
MDT approach: OT and PT.
NG tube.
Nursing care.
Counselling and parent support.
What is the management for Patau Syndrome?
Palliative care as most babies will die within the first 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 treatment: Congenital heart defect correction, grommets (significant secretory otitis media), plastic surgery (neck webbing), remove of gonads if present (50% malignant change).
Hormonal treatment:
- Growth hormone therapy.
- Oestrogen replacement therapy (12–15 years)
What is the management for Klinefelter Syndrome?
Conservative: SALT, educational and behavioral therapy, OT, PT and psychological therapy.
Medical: Fertility treatment, 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 and 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 and 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 longer than 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 the first 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 and healthy life. Life expectancy is reduced.
What is the prognosis for Klinefelter Syndrome?
Can live a normal and healthy life.
Previously associated with prison life.
What is prognosis for Prader-Willi syndrome?
Shortened life expectancy due to complications of morbid obesity and increased pain threshold.
