Chromosomal Abnormalities Flashcards
What is the mutation in Patau’s?
Trisomy 13
What is the clinical presentation of Patau’s?
- Microcephaly
- Micropthalmia
- Cleft Palate/ lip
- Polydactyly
- Omphalocele/ gastroschisis
- Cardiac defects (VSD, PDA, dextrocardia)
What is the mutation in Edward’s?
Trisomy 18
What is the presentation of Edward’s?
- Rocker bottom feet
- Overlapping fingers
- Intellectual disability
- Low-set ears
- Low birth weight
- Omphalocele/ gastroschisis
- Cardiac/ renal and GI abnormalities
What is the difference between an omphalocele and gastroschisis?
Omphalocele is covered with a membrane, gastroschisis is not
What is the mutation in Down’s syndrome?
Trisomy 21
What is the mutation in Noonan’s syndrome?
Mutated RAS/ Mitogen activated protein kinase
PTPN11 gene associated with pulmonary stenosis
RAF1 gene associated with cardiomyopathy
What is the presentation of Noonan’s?
- Webbed neck
- Trident hairline
- Cardiac (cardiomyopathy, pulmonary stenosis)
- Pectus excavatum
- Short stature
What is the mutation in Prader-Willi Syndrome?
Deletion PWS section of q arm chromosome 15
What is the difference between Prader Willi and Angelman’s syndrome?
Prader Willi is a lack of the paternal PWS region on chromosome 15
Angelman is a lack of maternal PWS region on chromosome 15
What is the presentation of Angelman syndrome?
- Cognitive impairment
- Ataxia
- Epilepsy (myoclonic seizures)
- Abnormal facial appearance
What is the presentation of PWS?
Fat, floppy, flacid
- Hypotonia
- Hyperphagia
- Almond-shaped eyes
- Obesity (in later childhood due to insatiable appetite)
- Hypogonadism
- Epicanthal folds
- Flat nasal bridge and upturned nose
- Intellectual disability
What is the mutation in Turner’s syndrome?
45X
What is the presentation of Turner’s syndrome?
- Short stature
- Primary amenorrhoea
- Delayed puberty (lack of 2ndary sexual characteristics)
- Widely spaced nipples
- Intellectual disability
- Webbed neck
- Infertility
- Hypothyroidism
- Omphalocele/ gastroschisis
- Bicuspid aortic valve > aortic coarctation (ESM over aortic valve)
What is the mutation in Klienfelter’s?
47XXY
What is the presentation of Klienfelter’s?
- Infertility
- Hypogonadism (microorchidism)
- Gynaecomastia
- Tall stature
What is the presentation of fragile X syndrome?
- IQ 20-80 (2nd most common cause of low IQ after down’s)
- Macrocephaly
- Macroorchidism
- Large, low set ears
- Long, thin face
- Autism
- Joint laxity
- Scoliosis
- Mitral valve prolapse
What is the mutation in fragile X syndrome?
CGG trinucleotide repeat expansion mutation (fragile)
FMR1 gene
What is the presentation of foetal alcohol syndrome?
- Microcephaly
- Absent philtrum
- Cardiac abnormalities
- Reduced IQ
- IUGR
- Small upper lip
What is the presentation of varicella in utero?
- Skin scarring
- Eye defects (micropthalmia)
- Neurological defects (low IQ, microcephaly)
What is the presentation of syphilis contracted in utero?
- Rhinitis
- Saddle-nose
- Sensorineural deafness
- Hepatosplenomegaly
- Jaundice
What is the inheritance pattern of Noonan’s?
Autosomal dominant
What is the management of PWS/ Angelman’s?
- Growth hormone if evidence of growth failure
- Management of feeding and obesity
What is the managment of Turner’s syndrome?
- Growth hormone therapy (plot heigh on syndrome specific growth charts)
- Oestrogen replacement (at time of puberty for development of secondary sexual characteristics)
How many TNT repeats are required for fragile X syndrome to develop?
> 200
Mutation is unstable and can expand between subsequent generations resulting in more severe forms of the disease
What is the most common chromosomal pathology causing Down’s syndrome?
Meiotic non-dysjunction (maternal age)
95% - error at meiosis, pair of chromosome 21 fails to separate
What is the 2nd most common chromosomal pathology causing down’s syndrome?
Translocation (5%)
Robertsonian translocation - extra chromosome 21 joined to another chromosome (usually 14)
Paternal chromosome analysis recommended - risk of recurrence 10-15% if mother is a translocation carrier
What is the 3rd most common translocation causing down’s syndrome?
Mosaicism (1%)
Milder phenotype, some cells normal some have trisomy 21
What is the immediate management of trisomy 21?
- ECG (AVSD) and evaluation by paediatricians (duodenal atresia)
- Genetic counselling
Early intervention programmes to reduce developmental delay:
- Physiotherapy - prevent abnormal compensatory movements for physical limitations
- Occupational therapy - fine motor and self-care
- SALT - speech intelligibility and manage language delay
What is the long-term management of trisomy 21?
- Annual hearing test, thyroid levels and ophthalmic evaluation (up to 5 years then every 2 years)
- Haemoglobin levels for IDA
- Monitor symptoms for OSA
- Monitor growth using updated Down’s syndrom growth charts
Which two syndromes (congenital) are associated with Wilm’s tumour development?
WAGR syndrome
Beckwith Weidermann syndrome
What is the presentation of WAGR syndrome?
W - Wilm’s tumour
A - Anaridia
G - GU malformations
R - Range of developmental delays
What is the presentation of Beckwith Weidermann syndrome?
- Large body habitus at birth
- Macroglossia
- Tall for age
