Syndromes And Genetics Flashcards
What is the most common underlying cause of Turner syndrome?
Nondysjunction in father as X is usually from mum
What form of Turner syndrome is more associated with learning disability?
Ring X
Physical appearance of Turner syndrome?
Short stature, increased weight Webbed neck (cystic hygroma) Low set ears Low posterior hairline Broad shield chest and widely spaced nipples Short 4th metacarpals, small fingernails
What is thought to cause the webbed neck in Turner syndrome?
Cystic hygroma
What sign at birth might suggest Turner syndrome?
Lymphoedema - swollen hands and feet
What is notable about the arms in Turner syndrome?
Wide carrying angle
What hormonal changes occur in Turner syndrome?
Anovulation and amennorhoea (hypo GnRH)
Often low T4 Hashimoto’s
DM 1 and 2 incidence both increased
What heart problems occur in Turner syndrome?
Aortic valve stenosis
Bicuspid aortic valve
Coarctation of aorta
PAVD
What do most 45XO foetuses do in utero?
Spontaneously terminate in 1st trimester
How is Noonan syndrome inherited?
AD
What is the most common underlying genetic defect causing Noonan syndrome?
RASopathy - mutations in the Ras/MAPK signalling pathways
What common syndrome is thought to have a risk of malignant hyperthermia and/or poor anaesthesia clearance associated with it?
Noonan syndrome
3 heart findings in Noonan syndrome?
Pulmonary stenosis
ASD/VSD
Hypertrophic cardiomyopathy
2 skin/lymph findings in Noonan syndrome?
Lymphoedema Webbed neck (cystic hygroma)
What may occur in boys with Noonan syndrome?
Cryptorchidism
What are the most common bleeding disorders that occur in Noonan syndrome?
Amegakaryocytic thrombocytopenia
vDW
APTT prolongation
Factor deficiencies
What malformation of brain is associated with Noonan syndrome?
Arnold chiari type 1
What facial appearance may suggest Noonan syndrome?
Webbed neck Hypertelorism Epicanthal folds Low set backwards rotated ears Deeply grooved philtrum, micrognathia, high arched palate
What is the technical term for wide carrying angle?
Cubitus valgus
What is the most common robertsonian translocation causing Down syndrome?
46XY;t(14q21q)
What facial features suggest Down syndrome?
Slanted eyes and epicanthal folds
Flat nasal bridge
Small mouth, macroglossia
Short neck
What nocturnal respiratory does Down syndrome carry and why?
OSA - relatively large tongue for small mouth which can block airway
What hands and feet changes occur in Down syndrome?
Single palmar crease
Big gap between 1st and 2nd toe
What neck problem occurs in Down syndrome?
Atlanto-axial joint instability possibly leading to cord injury
What eye sign is suggestive of Down syndrome?
Brushfield spots
Heart problems associated with Down syndrome?
AVSDs
Mitral valve problems
ToF, PDA
4 cancers that have higher risk in Down syndrome?
AML
ALL
Transient myeloproliferative disorders
Testicular cancer
What is the relative risk of solid organ tumours in people with Down syndrome?
Lower
GI changes associated with Down syndrome?
Hirschprungs disease Duodenal atresia Pyloric stenosis Imperforate anus Meckel diverticulum GORD Coeliac
What is the immune system like in Down syndrome?
Suppressed
What thyroid disturbances are common in syndromes e.g. Down, turner?
Often low - Hashimoto’s
What is Pompe disease?
Glycogen storage disorder type 2 - acid maltase deficiency due to GAA gene mutation, causing hypotonia myopathy hepatomegaly and HOCM within first few months of life. Treatment is myozyme - recombinant human GAA
What is the most common urea cycle defect?
OTC deficiency
What is the most severe urea cycle defect?
CPS1 deficiency
Give 3 organic acidaemias?
Methylmeluric aciduria
Isovaleric acidaemia
Maple syrup urine disease
What kind of acid base disturbance and other metabolic disturbances feature in organic acidaemias?
Metabolic acidosis
Ketotic hypglycaemia
Raised ammonia
What does VACTERL stand for?
Vertebral anomalies e.g. Butterfly vertebra Anorectal anomalies Cardiac defects TOF EOA Renal and radial abnormalities Limb defects
What does ‘smelly feet odour’ in unwell neonate suggest?
Isovalaeric acidaemia
What is primary HLH caused by?
AR gene mutations e.g. Perforin (PRF1)
3 things which might underlie secondary HLH? Particular infection?
Strong infection e.g. EBV
Immunodeficiency
Malignancy
What is HLH?
Cytokine storm disease characterised by uncontrolled proliferation and activation of lymphocytes/macrophages
When does HLH typically occur?
Within 1st year of life
What might typical signs and symptoms of HLH be?
Rash Jaundice Fever HSM Lymphadenopathy
What bone marrow picture does HLH cause?
Hypocellular causing low e.g. RBCs, neutrophils, platelets
What does HLH show on blood/lymph/marrow film?
Haemophagocytosis
What 3 blood markers might be altered in HLH?
Raised triglycerides
Low fibrinogen
Raised ferritin
Cure fo HLH?
BMT
What does CHARGE syndrome stand for?
Coloboma Heart defects Atresia of choana Retardation of growth and development Genital abnormalities Ear abnormalities
What underlies CHARGE syndrome?
AD inheritance of CHD7 mutation
Causes failure of growth of midline structures during 2nd month of gestation
6 syndromes which may feature radial abnormalities?
Thrombocytopenia-absent radius syndrome (TAP)
VACTERL
Edwards syndrome
Cornelia de Lange syndrome
Fanconi anaemia
Valproate or thalidomide exposure in utero
What is the Pierre Robin sequence?
Micrognathia leading to glossoptosis leading to airway obstruction
Often in the setting of cleft palate
4 syndromes associated with Pierre Robin sequence?
Fetal alcohol syndrome
Stickler syndrome
Di George/velocardiofacial syndrome
Treacher Collins syndrome
What is Stickler Syndrome?
AD collagen disorder causing flattened face with Pierre Robin sequence, underdeveloped midface
High myopic eyes, abnormal vitreous and cataracts/glaucoma
Hearing loss
Other hypermobility, scoliosis and MSK features etc.
What is Treacher Collins syndrome?
AD craniofacial disorder associated with Pierre Robin, downward slanting eyes with lower lid coloboma and abnormal ears/hearing loss
What is Moebius syndrome?
Congenital absence of CNS 6 and 7 plus or minus 5, 9, 10 and 12
Plus upper body weakness, dental problems/high palate, syndactyly, hearing problems
What is Haddad syndrome and what gene is associated?
Ondine’s curse plus Hirschprungs disease in setting of PHOX2B mutation
What is the pentalogy of Cantrell?
Exomphalos Cleft sternum Anterior diaphragmatic hernia Heart defects incl ectopia cordis Pericardial agenesis
