Paediatric genetic conditions Flashcards
Explain mitochondrial inheritance
- Mitochondrial DNA is primarily from the mother.
- All of the mitochondria in the sperm are in the tail, which does not enter the egg
Explain the cause of Down’s syndrome
- Trisomy 21
- 3 copies of chromosome 21
What are the dysmorphic features seen in Down’s syndrome
- Hypotonia
- Brachycephaly
- Prominent epicanthic folds
- Upward sloping palpebral fissures
- Single palmar crease
- Short neck
- Short stature
- Flattened face and nose
- Brushfield spots in iris
what are the screening tests involved in Down’s to determine the need for more invasive tests?
- Combined test
- Triple test
- Quadruple test
what is the first line screening test for Downs and what does it involve?
- Combined
- Done between 11 and 14 wks
- Combines USS for nuchal translucency and maternal bloods
What outcome of the combined test would suggest increased risk of Down’s
- USS -> nuchal thickness >6mm
- Bloods : higher beta-HCG and lower pregnancy-associated plasma protein-A (PAPPA)
When is the triple test done and what does it involve ?
- Between 14 and 20 weeks
- Beta-HCG : higher result indicates greater risk.
- Alpha-fetoprotein (AFP) : lower result indicates a greater risk.
- Serum oestriol : lower result indicates a greater risk.
What is the quaruple test and when is it done
- Between 14 and 20 weeks
- Same as triple but involves inhibin-A
- Higher inhibin-A = greater risk
When is more invasive antenatal testing for Down’s done ?
- If the screening suggests a risk of greater than 1 in 150
What two tests are involved in antenatal testing for Down’s and when is it done ?
- Chorionic villus sampling (before 15 wks)
- Amniocentesis : later in pregnancy
what two GI conditions are seen in children with Down’s
- Duodenal atresia
- Hirschsprung’s
what cardiac complications are seen in children with Downs’
- VSD
- ASD
- Tetralogy of fallot
- PDA
what other complications are seen in people with Down’s
- LD
- Recurrent otitis media
- Deafness (due to glue ear)
- Hypothyroid
- Atlantoaxial instablility
- Leukaemia (ALL)
- Dementia
What members of the MDT are involved in the care of a child with Down’s ?
- OT
- Speech and language therapy
- Physiotherapy
- Dietician
- Paediatrician
- GP
- Health visitors
- Cardiologist for congenital heart disease
- ENT specialist for ear problems
- Audiologist for hearing aids
- Optician for glasses
- Social services for social care and benefits
- Additional support with educational needs
- Charities such as the Down’s Syndrome Association
What is the chromosomal make up of someone with Klinefelter syndrome ?
Male with an extra X chromsome (47XXY)
What features are seen in Kleinfelter’s after puberty ?
- Taller height
- Wider hips
- Gynaecomastia
- Weaker muscles
- Small testicles
- Reduced libido
- Shyness
- Infertility
- Subtle learning difficulties (particularly affecting speech and language)
How are turner’s and Klinefelters diagnosed ?
- Karyotype
How is someone with Klinefelter’s supported ?
- Testosterone injections
- IVF
- Breast reduction
MDT input : - Speech and language therapy
- OT
- Physio to strengthen muscles and joints
- Educational support where required for dyslexia and other learning difficulties
What chromosomal abnormality is seen in someone with Turner’s ?
- Female with single X chromosome (45XO)
What are the features of someone with Turner’s ?
- Short stature
- Webbed neck
- Broad chest with widely spaced nipples
- High arching palate
- Downward sloping eyes with ptosis
- Broad chest with widely spaced nipples
- Cubitus valgus
- Underdeveloped ovaries with reduced function
- Late or incomplete puberty (ammenorrhoea)
What cardiac conditions are seen in women with Turner’s ?
- Bicuspid aortic valve and coarctation of the aorta = ejection systolic murmur
- Increased risk of aortic dilation and dissection = regular monitoring
what are the other associated conditions in a woman with Turner’s ?
- Recurrent otitis media
- Recurrent UTI
- Hypothyroidism
- Hypertension
- Obesity
- Diabetes
- Osteoporosis
what is the most common renal abnormality in women with Turner’s syndrome ?
Horseshoe kidney
What is the inheritance of Noonan Syndrome ?
Autosommal dominant
What are the features of Noonan ?
- ‘Male’ Turner’s
- Short stature
- Webbed neck
- Widely spaced nipples
- Broad forehead
- Downward sloping eyes with ptosis
- Hypertelorism
- Prominent nasolabial folds
- Low set ears
what heart defect is associated with Noonan’s ?
- PULMONARY VALVE STENOSIS
- Hypertrophic cardiomyopathy
- ASD
What other conditions are associated with Noonan’s ?
- Cryptorchidism
- LD
- Bleeding disorders (factor XI deficiency)
- Lymphoedema
- Increased risk of leukaemia and neuroblastoma
Explain the inheritance of Marfan’s
- Autosommal dominant connective tissue disorder effect fibrillin
- Defect in FBN1 gene on chromosome 15
Explain the features seen in Marfan’s
- Tall stature
- Long neck
- Long limbs
- Arachnodactyly
- High arch palate
- Hypermobility
- Pectus carinatum or pectus excavatum
- Downward sloping palpable fissures
what cardiac conditions are associated with marfan’s
- Mitral valve prolpase with regurg
- Aortic valve prolapse with regurg
- Aortic aneurysms
what other conditions are associated with Marfan’s ?
- Lens dislocation in the eye
- Joint dislocations and pain due to hypermobility
- Scoliosis of the spine
- Repeated pneumothorax
- GORD
What is the most important aspect of management in someone with Marfan’s
- Minimise BP and HR due to risk of AA
- Lifestyle advice + BB and ACEIs
Explain the inheritance of Fragile X syndrome ?
- X linked, trinucleotide repeat disorder
- Mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome
What are the features of fragile X ?
- Intellectual disability
- Long, narrow face
- Large ears
- Large testicles after puberty
- Hypermobile joints
- ADHD
- Autism
- Seizures
what cardiac condition is seen in children with fragile X syndrome ?
Mitral valve prolapse
Explain the inheritance of Prader-Willi syndrome
- Absence of Prader-Willi gene on long arm of chromosome 15 (paternal)
what are the features of Prader-Willi syndrome ?
- Constant insatiable hunger that leads to obesity
- Hypotonia
- Mild-moderate learning disability
- Hypogonadism
- Fairer, soft skin that is prone to bruising
- Mental health problems, particularly anxiety
- Dysmorphic features
- Narrow forehead
- Almond shaped eyes
- Strabismus
- Thin upper lip
- Downturned mouth
what medication is used in the management of Prader-Willi, focusing on impriving muscle development and body composition ?
- Growth hormone
Explain the is the inheritance of Angelman
- Loss of function of UBE3A gene, inherited from the mother
What are the features of Angelman syndrome
- Fascination with water
- Happy demeanour
- Inappropriate laughter
- Hand flapping
- Widely spaced teeth
- Delayed development and LD
- Severe delay or absence of speech development
- Ataxia
Explain the cause of William’s syndrome
Deletion of genetic material on one copy of chromosome 7
What are the features of William’s syndrome ?
- Starburst eyes
- Friendly and sociable personality
- Elfin-like facies
- Learning difficulties
Give 4 associated conditions with William’s syndrome
- Supravalvular aortic stenosis
- ADHD
- Hypertension
- Hypercalcaemia
Give 4 key features of Patau syndrome + its cause
- Trisomy 13
- Microcephalic, small eyes
- Cleft lip / palate
- Polydactyly
- Scalp lesions
Give 4 features of Edwards’s syndrome + its cause
- Trisomy 18
- Micrognathia
- Low-set ears
- Rocker bottom feet
- Overlapping features
Give 3 features of Pierre-Robin syndrome
- Micrognathia
- Posterior displacement of tongue -> upper airway obstruction
- Cleft palate
Give 5 features of Cri du chat syndrome
- Characteristic cry
- Feeding difficulties and poor weight gain
- LD
- Microcephaly and micrognathism
- Hypertelorism
What is seen on bloods in someone with Turner’s
- Raised FSH/LH in primary amenorrhoea
