Genetics Flashcards
What chromosomal abnormality causes Patau’s syndrome?
Trisomy 13
What are the features of Patau’s syndrome?
- Cardiac defects = VSD, PDA, dextrocardia
- Microcephaly and brain defects
- Microphthalmia (small eyes)
- Other eye defects
- Cleft lip/palate
- Polydactyl
- Omphalocele / Gastroschisis (abdominal wall defects)
What chromosomal abnormality causes Edward’s syndrome?
Trisomy 18
What are the features of Edward’s syndrome?
- LBW
- Small mouth/chin
- Low-set ears
- ‘Rocker-bottom’ feet
- Overlapping fingers
- Intellectual disability
- Cardiac, renal and GI abnormalities
- Omphalocele / Gastroschisis (abdominal wall defects)
What chromosomal abnormality causes Down’s syndrome?
Trisomy 21
What are the features of Down’s syndrome?
- Characteristic facies
- Hypotonia and short neck
- Single palmar crease
- ‘Sandal gap’ on feet
- Short stature
- Upslanting palpebral fissures
- Flat occiput
- Congenital heart defects in 40%
- Omphalocele / Gastroschisis (abdominal wall defects)
What genetic abnormality causes Noonan’s syndrome?
Mutated RAS/Mitogen Activated Protein Kinase
What are the features of Down’s syndrome?
- Webbed neck
- Trident hairline
- Pectus excavatum
- Short stature
- Pulmonary stenosis
- Low IQ - most common cause
What genetic abnormality causes Prader-Willi syndrome?
Lacks paternal 15q
What genetic abnormality causes Angelman’s syndrome?
Lacks maternal 15q
What are the features of Prader-Willi syndrome?
- Hypotonia
- Hyperphagia
- Almond-shaped eyes
- Fat, floppy, flaccid
- Hypogonadism
- Obesity (in later childhood)
- Epicanthal folds
- Flat nasal bridge + upturned nose
- Learning disability
What are the features of Angelman syndrome?
- Cognitive impairment
- Ataxia
- Epilepsy
- Abnormal facial appearance
- Myoclonic seizures
What chromosomal abnormality causes Turner’s syndrome?
45 X
What are the features of Turner’s syndrome?
- Lymphoedema of hands/feet in neonate
- Short stature, spoon-shaped nails
- Wide carrying angle
- Thick or webbed neck
- Infertility
- Bicuspid aortic valve > Aortic coarctation
- ESM over aortic valve
- Delayed puberty / Infertility
- Hypothyroidism
- Omphalocele / Gastroschisis (abdominal wall defects)
What chromosomal abnormality causes Klinefelter’s syndrome?
47 XXY
What are the features of Klinefelter’s syndrome?
- Infertility
- Hypogonadism (small testicles)
- Gynaecomastia
What genetic abnormality causes Fragile X syndrome?
CGG trinucleotide repeat expansion mutation (fragile) to the FMR1 gene
What are the features of Fragile X syndrome?
- IQ 20-80 (mean 50) – 2nd most common cause of low IQ after Down’s Syndrome
- Macrocephaly
- Macroorchidism
- Characteristic facies
- Large, low-set ears
- Long, thin face
- Other – autism, joint laxity, scoliosis
- Mitral valve prolapse - common complication
Define Malformation.
Primary structural defect occurring during the development of a tissue/organ.
Define Defomration.
Abnormal intrauterine mechanical force that distorts a normally formed structure (e.g. oligohydramnios).
Define Disruption.
Destruction of a foetal part that may have initially formed normally.
Define Dysplasia.
Abnormal cellular organisation or function.
Define Single System Defect.
Single congenital malformations.
Define Sequence.
Pattern of multiple abnormalities occurring after one initiating defect - i.e. posterior urethral valves.
Define Association.
Group of malformations that occur together but in different combinations case to case.
Define Syndrome.
Multiple abnormalities occurring repeatedly in a consistent pattern, common underlying causal mechanism.
What are the signs and symptoms of foetal alcohol syndrome?
- Microcephaly
- Absent philtrum
- Cardiac abnormalities
- Reduced IQ
- IUGR
- Small upper lip
What are the signs and symptoms of cigarette smoking in pregnancy?
- IUGR
- Miscarriage
- Stillbirth
What are the signs and symptoms of syphilis infection in a neonate?
- Rhinitis
- Saddle-nose
- Deafness (sensorineural)
- Hepatosplenomegaly
- Jaundice
What is the prognosis of Patau’s syndrome?
- 80% die in first month of life
- 90% by 1 year of age
What are the appropriate investigations for suspected Patau’s syndrome?
- USS analysis in 2nd trimester
- Chromosomal analysis from amniocentesis/cffDNA
What is the prognosis of Edward’s syndrome?
Many will die in infancy → prolonged survival is possible
What are the appropriate investigations for suspected Edward’s syndrome?
- USS analysis in 2nd trimester
- Chromosomal analysis from amniocentesis/cffDNA
What is the prognosis of Noonan’s syndrome?
- Penetrance varies greatly
- From lethal prenatally to minimal morbidity
What is the management of Prader-Willi syndrome?
- Growth hormone if clinical evidence of growth failure
- Management of feeding and obesity (i.e. lock cupboards)
What are the signs and symptoms of neonatal Turner’s syndrome?
- Pyloric stenosis
- Cardiac problems
- Coarctation of aorta
- Bicuspid aortic valve
- AS murmur = ESM over aortic valve
- Renal anomalies
- Cystic hygroma - may resolve early → skin on the back of the neck
Name 3 trinucleotide repeat-expansion mutations.
- Fragile X syndrome
- Myotonic dystrophy
- Huntington disease
What is the chromosomal pathogenesis of Down’s syndrome?
-
Meiotic non-disjunction - linked to maternal age
- Error at meiosis, pair of chromosomes 21 fail to separate (one gamete has 2 x 21 and one has none)
- 94%
- No need to examine parental chromosome
-
Translocation
- Extra chromosome 21 is joined to another chromosome (usually 14)
- Robertsonian translocation
- 5%
- Parental Chr analysis is recommended
- Risk of recurrence 10-15% if mother is translocation carrier
-
Mosaicism
- Milder phenotype, some cells are normal, and some have trisomy 21, formation of chromosomally normal zygote but non-disjunction at mitosis
- 1%
What are the craniofacial signs of Down’s syndrome?
- Round face
- Flat nasal bridge
- Epicanthic folds
- Brushfield spots in iris
- Small mouth
- Small ears
- Flat occiput
- 3rd fontanelle
- Short neck
- Single palmar crease
- Sandal-gap
- Hypotonia
What are the medical problem present at birth in Down’s syndrome?
- Congenital heart defects - 40%
- Duodenal atresia
- Hirschprung’s disease
- Omphalocele ± umbilical hernia
What are the medical problem present later if life in Down’s syndrome?
- Delayed motor milestones
- Learning difficulty / Low IQ
- Short stature
- Secretory otitis media (75%)
- Visual impairment (25-50%)
- OSA (50-75%)
- Increased disease chance:
- Leukaemia (not ALL)
- Hypothyroidism
- Coeliac’s
- Epilepsy
- Early-onset Alzheimer’s
- Joint laxity - screen for atlantoaxial instability in those doing sports → risk of neck dislocation
What congenital conditions are associated with Down’s syndrome?
- Kostmann’s syndrome
- Bloom syndrome
- Fanconi syndrome / Diamond-Blackfan
- NF1
- Li Fraumeni syndrome
What is the management of Down’s syndrome at birth?
- Echocardiogram - AVSD
- Evaluation by paediatricians - duodenal atresia
- Genetic counselling
- Early intervention programmes if developmental delay is present
- Physiotherapy → prevent abnormal compensatory movements for physical limitations
- OT → fine motor and self-care
- SALT → speech intelligibility and to manage language delay
What is the management of Down’s syndrome in children?
- Annual tests
- Hearing test
- Thyroid levels
- Ophthalmic evaluation (up to 5 years then every 2 years)
- Appropriate education with an individualised educational plan
- Haemoglobin level for IDA
- Monitor for symptoms of sleep apnoea
- Monitor growth using updated Down’s syndrome growth charts
