Paediatric genetics Flashcards
When does Turner’s syndrome occur?
when a female has a single X chromosome, making them 45 XO
What is the life expectancy of someone with Turner’s syndrome?
close to normal
What are the three main features of Turner’s syndrome to look out for in exams?
short stature, webbed neck and widely spaced nipples.
Apart from short stature, webbed neck and widely spaced nipples, what other features do you see in Turner’s syndrome?
High arching palate
Downward sloping eyes with ptosis
Cubitus valgus
Underdeveloped ovaries with reduced function
Late or incomplete puberty
Most women are infertile
What is cubitus valgus?
abnormal feature of the elbow. When the arm is extended downwards with the palms facing forward, the angle of the forearm at the elbow is exaggerated, angled away from the body
What conditions are associated with Turner’s syndrome?
Recurrent otitis media
Recurrent urinary tract infections
Coarctation of the aorta
Hypothyroidism
Hypertension
Obesity
Diabetes
Osteoporosis
Various specific learning disabilities
How do you help prevent short stature in Turner’s syndrome?
Growth hormone therapy
How can you help establish female secondary sex characteristics, regulate the menstrual cycle and prevent osteoporosis in females with Turner’s syndrome?
Oestrogen and progesterone
How can you increase the chance of a woman with Turner’s syndrome of becoming pregnant?
Fertility treatment
What is the most common cause of Primary Amenorrhoea?
Turner’s syndrome
What is Down’s syndrome also known as?
Trisomy 21
Why is Down’s syndrome also known as Trisomy 21?
Because it is caused by three copies of chromosome 21.
What dysmorphic features are seen in Down’s syndrome?
Hypotonia (reduced muscle tone)
Brachycephaly (small head with a flat back)
Short neck
Short stature
Flattened face and nose
Prominent epicanthic folds
Upward sloping palpebral fissures
Single palmar crease
Low set ears
What are epicanthic folds?
folds of skin covering the medial portion of the eye and eyelid
What are palpebral fissures?
gaps between the lower and upper eyelid
What are the complications of Down’s syndrome?
Learning disability
Recurrent otitis media
Deafness. Eustachian tube abnormalities lead to glue ear and conductive hearing loss.
Visual problems such myopia, strabismus and cataracts
Hypothyroidism
Cardiac defects
Atlantoaxial instability
Leukaemia is more common in children with Down’s
Dementia is more common in adults with Down’s
What cardiac defects are most common in those with Down’s syndrome?
ASD, VSD, patent ductus arteriosus and tetralogy of Fallot
What are the three tests for Down’s syndrome?
Combined test, triple test and quadruple test
What is the first line and most accurate test for Down’s syndrome?
The combined test- combines ultrasound and maternal blood tests
When is the Down’s combined test performed?
Between 11-14 weeks of gestation
What does the ultrasound measure in the combined test for Down’s syndrome?
Measures nuchal translucency, which is the thickness of the back of the neck of the foetus. (thickened in Down’s)
What thickness is the nuchal translucency in Down’s?
Over 6mm
What in the maternal blood will indicate that a child will have a higher risk of Down’s in the combined test?
A higher level of Beta‑human chorionic gonadotrophin (beta-HCG) or a lower level of Pregnancy‑associated plasma protein‑A (PAPPA)
When is the triple test for Down’s performed?
14-20 weeks of gestation- just maternal blood tests
What in the maternal blood will indicate that a child will have a higher risk of Down’s in the triple test?
Beta-HCG. A higher result indicates greater risk.
Alpha-fetoprotein (AFP). A lower result indicates a greater risk.
Serum oestriol (female sex hormone). A lower result indicates a greater risk.
When is the quadruple test for Down’s performed?
Between 14 and 20 weeks of gestation
What is included in the quadruple test for Down’s that isn’t in the triple test?
Inhibin-A
Does a higher or lower level of inhibin A indicate a higher risk for Down’s?
Higher
What procedure is a woman offered in their child has a greater than 5% chance of having Down’s?
amniocentesis or chorionic villus sampling
What does chronic villus sampling involve?
an ultrasound guided biopsy of the placental tissue. This is used when testing is done earlier in pregnancy (before 15 weeks).
What does amniocentesis involve?
ultrasound guided aspiration of some amniotic fluid using a needle and syringe. This is later in pregnancy once there is enough amniotic fluid to make it safer to take a sample.
What is the relatively new test for detecting abnormalities in the fetus during pregnancy?
Non-invasive prenatal testing (NIPT)
What are the regular follow up investigations that are important for children with Down’s?
Regular thyroid checks (2 yearly)
Echocardiogram to diagnose cardiac defects
Regular audiometry for hearing impairment
Regular eye checks
What does the combined test for Down’s include?
Ultrasound, beta-HCG and PAPPA
What is included in the triple test for Down’s?
Beta-HCG (raised), AFP (low), Serum oestriol (low)
What is included in the quadruple test for Down’s?
Beta-HCG, AFP, serum oestriol and inhibin-A (high)
What is the average life expectancy of someone with Down’s?
60 years
What is fragile X syndrome?
a mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome
What does the FMR1 gene code for?
the fragile X mental retardation protein, which plays a role in cognitive development in the brain
Is fragile X x-linked and is it dominant or recessive?
X linked but we don’t know if it is dominant or recessive
Which gender is affected by Fragile X syndrome?
Males are always affected, females vary in how much they are affected
What are the features of Fragile X syndrome?
Delay in speech and language development. Other features are:
Intellectual disability
Long, narrow face
Large ears
Large testicles after puberty
Hypermobile joints (particularly in the hands)
Attention deficit hyperactivity disorder (ADHD)
Autism
Seizures
What is the life expectancy of someone with Fragile X syndrome?
Similar to general population depending on disabilities and complications
Is CF dominant or recessive?
Recessive
What is CF caused by?
a genetic mutation of the cystic fibrosis transmembrane conductance regulatory gene on chromosome 7
What is the most common variant of CF?
delta-F508
What is delta-F508 for?
cellular channels, particularly a type of chloride channel
What percentage of people are carriers of CF?
1 in 25
What percentage of children have CF?
1 in 2500
What are the key consequences of CF?
Thick pancreatic and biliary secretions that cause blockage of the ducts, resulting in a lack of digestive enzymes such as pancreatic lipase in the digestive tract
Low volume thick airway secretions that reduce airway clearance, resulting in bacterial colonisation and susceptibility to airway infections
Congenital bilateral absence of the vas deferens in males. Patients generally have healthy sperm, but the sperm have no way of getting from the testes to the ejaculate, resulting in male infertility
Both parents are healthy, one sibling has cystic fibrosis and a second child does not have the disease, what is the likelihood of the second child being a carrier
We know the child doesn’t have the condition, so the answer is two in three.
How is CF screened for at birth?
Newborn bloodspot test
What is often the first sign of CF?
Meconium Ileus
What is meconium Ileus?
In about 20% of babies with CF, the meconium is thick and sticky, causing it to get stuck and obstruct the bowel. This is called meconium ileus, and is practically pathognomonic for cystic fibrosis. This presents as not passing meconium within 24 hours, abdominal distention and vomiting.
What can CF present with later in childhood if not identified at birth?
recurrent lower respiratory tract infections, failure to thrive or pancreatitis
What are the symptoms of CF?
Chronic cough
Thick sputum production
Recurrent respiratory tract infections
Loose, greasy stools (steatorrhoea) due to a lack of fat digesting lipase enzymes
Abdominal pain and bloating
Parents may report the child tastes particularly salty when they kiss them, due to the concentrated salt in the sweat
Poor weight and height gain (failure to thrive)
What are the causes of clubbing in in children?
Hereditary clubbing
Cyanotic heart disease
Infective endocarditis
Cystic fibrosis
Tuberculosis
Inflammatory bowel disease
Liver cirrhosis
What are the signs of cystic fibrosis?
Low weight or height on growth charts
Nasal polyps
Finger clubbing
Crackles and wheezes on auscultation
Abdominal distention
What is the gold standard test for CF?
Sweat test
How can tests for CFTR gene be performed during pregnancy?
amniocentesis or chorionic villous sampling
What is applied to the skin in the sweat test for CF?
Pilocarpine
What is the diagnostic chloride concentration in the sweat test for CF?
more than 60mmol/l
What are all the common colonisers for bacterial infections in those with CF?
Staphylococcus aureus
Haemophilus influenza
Klebsiella pneumoniae
Escherichia coli
Burkhodheria cepacia
Pseudomonas aeruginosa
What are the two key colonisers for bacterial infections in those with CF?
staph aureus and pseudomonas
What do people with CF take to prevent staph aureus infections?
Long term prophylactic flucloxacillin
Colonisation of what leads to a worse prognosis for those with CF?
Pseudomonas
Why is pseudomonas infection bad for those with CF?
It often becomes resistant to anitbiotics and leads to significantly increased morbidity and mortality
What is pseudomonas treated with in those with CF?
long term nebulised antibiotics such as tobramycin. Oral ciprofloxacin is also used.
What is used to help CF patients to digest fats in patients with pancreatic insufficiency?
CREON tablets
What can break down DNA material in respiratory secretions, making secretions less viscous and easier to clear to help those with CF?
Nebulised DNase (dornase alfa)
What are patients with CF monitored for?
diabetes, osteoporosis, vitamin D deficiency and liver failure.
What is the life expectancy for people with CF?
median life expectancy of 47 years
What is the management for CF?
Chest physiotherapy several times a day is essential to clear mucus and reduce the risk of infection and colonisation
Exercise improves respiratory function and reserve, and helps clear sputum
High calorie diet is required for malabsorption, increased respiratory effort, coughing, infections and physiotherapy
CREON tablets to digest fats in patients with pancreatic insufficiency (these replace the missing lipase enzymes)
Prophylactic flucloxacillin tablets to reduce the risk of bacterial infections (particularly staph aureus)
Treat chest infections when they occur
Bronchodilators such as salbutamol inhalers can help treat bronchoconstriction
Nebulised DNase (dornase alfa) is an enzyme that can break down DNA material in respiratory secretions, making secretions less viscous and easier to clear
Nebulised hypertonic saline
Vaccinations including pneumococcal, influenza and varicella
What is the main type of muscular dystrophy?
Duchennes muscular dystrophy
What are the genetics behind Duchenne muscular dystrophy?
Inherited X linked recessive disorder resulting from a deletion on the short arm of the X chromosome
What is the pathophysiology behind duchenne muscular dystrophy?
The site of the deletion codes for a protein called dystrophin which normally connects the cytoskeleton of muscle fibres to the extracellular matrix through the cell membrane therefore deficiency results in myofibre necrosis and raised serum CPK
What are the types of muscular dystrophy?
Duchennes muscular dystrophy
Beckers muscular dystrophy
Myotonic dystrophy
Facioscapulohumeral muscular dystrophy
Oculopharyngeal muscular dystrophy
Limb-girdle muscular dystrophy
Emery-Dreifuss muscular dystrophy
What is the name for when children with proximal muscle weakness use a specific technique to stand up from a lying position?
Gower’s sign
What is Gower’s sign?
To stand up, they get onto their hands and knees, then push their hips up and backwards like the “downward dog” yoga pose. They then shift their weight backwards and transfer their hands to their knees. Whilst keeping their legs mostly straight they walk their hands up their legs to get their upper body erect. This is because the muscles around the pelvis are not strong enough to get their upper body erect without the help of their arms.
What is duchennes muscular dystrophy caused by?
a defective gene for dystrophin on the X-chromosome
What is dystrophin?
a protein that helps hold muscles together at the cellular level
Is duchennes muscular dystrophy x-linked dominant or x-linked recessive?
X- linked recessive
Which gender usually presents with Duchennes muscular dystrophy?
Males
At what age and how do boys usually present with Duchennes muscular dystrophy?
3-5 years with weakness in the muscles around their pelvis
What is the life expectancy of someone with Duchennes muscular dystrophy?
25-35 years
What can slow the progression of muscle weakness by 2 years and improve muscle strength?
Oral steroids and creatine
What is the difference between Duchennes and Becker’s muscular dystrophy?
The dystrophin gene is less severely affected and maintains some of its function in Becker’s
What is the difference between time of onset of Duchennes and Becker’s muscular dystrophy?
Duchennes presents are around 3-5 years whereas Becker’s presents around 8-12 years.
What is myotonic dystrophy?
Myotonic dystrophy is a genetic disorder that usually presents in adulthood
What are the features of myotonic dystrophy?
Progressive muscle weakness
Prolonged muscle contractions
Cataracts
Cardiac arrhythmias
What is the key feature of myotonic dystrophy to remember for exams?
prolonged muscle contraction
How might prolonged muscle contraction in myotonic dystrophy present?
A patient that is unable to let go after shaking someone’s hand, or unable to release their grip on a doorknob after opening a door
Hoe does Facioscapulohumeral Muscular Dystrophy usually present?
presents in childhood with weakness around the face, progressing to the shoulders and arms
What is a classic initial symptom of Facioscapulohumeral Muscular Dystrophy
sleeping with their eyes slightly open and weakness in pursing their lips. They are unable to blow their cheeks out without air leaking from their mouth.
How does Oculopharyngeal Muscular Dystrophy usually present?
presents in late adulthood with weakness of the ocular muscles (around the eyes) and pharynx (around the throat). typically presents with bilateral ptosis, restricted eye movement and swallowing problems. Muscles around the limb girdles are also affected to varying degrees.
How does Limb-girdle Muscular Dystrophy usually present?
presents in teenage years with progressive weakness around the limb girdles (hips and shoulders).
How does Emery-Dreifuss Muscular Dystrophy usually present?
presents in childhood with contractures, most commonly in the elbows and ankles. Patients also suffer with progressive weakness and wasting of muscles, starting with the upper arms and lower legs.
What are the clinical presentations in duchenne muscular dystrophy?
Waddling gait + slow at running + mount stairs one by one
Language delay
Gower’s sign-they need to turn prone to rise from the floor
Pseudohypertrophy of the calves as the muscular tissue is replaced by fat
Boys will be slower and clumsier than their peers
What is the management for duchenne muscular dystrophy?
Exercises
Night splints
Good sitting posture to reduce scoliosis
Corticosteroids can help prevent scoliosis
What is Prader-Willi caused by?
the loss of functional genes on the proximal arm of the chromosome 15 inherited from the father. This can be due to a deletion of this portion of the chromosome, or when both copies of chromosome 15 are inherited from the mother.
What are the features of Prader-Willi syndrome?
Constant insatiable hunger that leads to obesity
Poor muscle tone as an infant (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 is the key feature of Prader-Willi syndrome?
Insatiable hunger
What treatment for Prader-Willi syndrome is aimed at improving muscle development and body composition?
Growth hormone
Are the majority of cases of noonan autosomal dominant or recessive?
Autosomal dominant
What are the features of Noonan syndrome?
Short stature
Broad forehead
Downward sloping eyes with ptosis
Hypertelorism (wide space between the eyes)
Prominent nasolabial folds
Low set ears
Webbed neck
Widely spaced nipples
What conditions are associated with Noonan syndrome?
Congenital heart disease, particularly pulmonary valve stenosis, hypertrophic cardiomyopathy and ASD
Cryptorchidism (undescended testes) can lead to infertility. Fertility is normal in women.
Learning disability
Bleeding disorders
Lymphoedema
Increased risk of leukaemia and neuroblastoma
What is the main complication of Noonan syndrome?
congenital heart disease
When does Klinefelter syndrome occur?
when a male has an additional X chromosome, making them 47 XXY
What are the features of Klinefelter syndrome?
Usually patients with Kleinfelter syndrome appear as normal males until puberty. At puberty can develop features suggestive of the condition:
Taller height
Wider hips
Gynaecomastia
Weaker muscles
Small testicles
Reduced libido
Shyness
Infertility
Subtle learning difficulties (particularly affecting speech and language)
What treatment in Klinefelter syndrome improves many of the symptoms?
Testosterone injections
What is the life expectancy in Klinefelter syndrome?
Close to normal
What are the complications of Klinefelter syndrome?
Higher breast cancer risk compared with other males (but still less than females)
Osteoporosis
Diabetes
Anxiety and depression
What is Angelman syndrome?
a genetic condition caused by loss of function of the UBE3A gene, specifically the copy of the gene that is inherited from the mother. This can be caused by a deletion on chromosome 15, a specific mutation in this gene or where two copies of chromosome 15 are contributed by the father, with no copy from the mother
What are the features of Angelman syndrome?
Delayed development and learning disability
Severe delay or absence of speech development
Coordination and balance problems (ataxia)
Fascination with water
Happy demeanour
Inappropriate laughter
Hand flapping
Abnormal sleep patterns
Epilepsy
Attention-deficit hyperactivity disorder
Dysmorphic features
Microcephaly
Fair skin, light hair and blue eyes
Wide mouth with widely spaced teeth
What are the main features of Angelman syndrome to remember?
unusual fascination with water, happy demeanour and widely spaced teeth
What is William syndrome caused by?
microdeletion on one copy of chromosome 7 resulting in a single copy of the gene- usually random
What are the features of William syndrome?
elfin-like features
Starburst eyes (star like pattern on the iris)
Broad forehead
Flattened nasal bridge
Wide mouth with widely spaced teeth
Small chin
characteristic like affect - very friendly and social, trusting
learning difficulties
short stature
What are the distinctive features of William syndrome?
Very sociable
Starburst eyes
wide mouth with big smile
What are the complications of William syndrome?
Supraventricular aortic stenosis
ADHD
Hypertension
Hypercalcaemia
Where is the problem in Edwards Syndrome?
Trisomy 18
What is the clinical presentation of Edward’s syndrome?
Low birthweight
Small mouth and chin
Short sternum
Flexed, overlapping fingers
Rocker-bottom feet
Cardiac and renal malformations
Where is the problem in patau syndrome?
Trisomy 13
What is teh clinical presentation of Patau syndrome?
Structural defects of the brain
Scalp defects
Small eyes and other eye defects
Cleft lip and palate
Polydactyly
Cardiac and renal malformations
