GENETIC SYNDROMES/MULTI SYSTEM CONDITIONS Flashcards
MOST common associations with PATAU syndrome (Trisomy 13)
Holoprosencephaly (40-50%)
Polydactyly (70%)
Of the three most common trisomies which one has the highest incidence of major structural anomalies?
18 - Edwards syndrome
What are the most common findings of trisomy 18
CHD (90-95%)
CNS or spinal abnormalities (70%)
- choroid plexus cyst, agenesis of CC
- Dandy walker continuum
- Neural tube defects (20%) spina bifida (myelomeningocele)
IUGR (60-90%) seen early
Cystic hygroma (20%)
clenched hand over overlapping 2nd/3rd digits (80%)
Single umbilical artery (80%)
Omphalocele (20-25%)
DOWNS syndrome - most common cause?
meiotic non disjunction - 95% of cases
Downs have increased incidence of what cancer
Leukaemia - AML
What are the 3 ways triploidy 69 chromosomes occurs?
Failure of division of meiosis I or II in the sperm
Failure of division of meiosis I or II in oocyte
Dispermy - fertilisation of one egg by 2 sperms.
What is the clinical triad of Aicardi syndrome ?
x-linked genetic defect - FATAL in males
salaam seizures
CC dysgenesis
Chorioretinal Lacunae - pathognomonic
MOST common cause of hereditary cholestasis ?
Alagille syndrome
JAG1 mutation 90%
MOST common genetic cause of emphysema and metabolic liver disease.
A1-AT deficiency
basal predominant panlobular emphysema
Ataxia Telangiectasia has increased risk of which cancers?
bowel and breast
MOST common overgrowth and cancer predisposition syndrome? What cancers are it associated with?
Beckwith Wiedemann syndrome
Wilms
hepatoblastoma
neuroblastoma
rhabdomyosarcoma
MOST common associations of Crouzon syndrome
Chairi I (70%)
Stylohyoid ligament calcification >4yrs (50%)
Classical TRIAD of HHT and most common locations
Epistaxis
Multiple telangiectasias
Positiev Family History
Most common associations with Joubert syndrome
MCDK (30%)
Polydactyly (15%)
Coloboma, retinal dysplasia
Maffuci syndrome is more common in males but associated with what 2 conditions?
Juvenile Granulosa tumour of the ovary
Colorectal haemangioma
What condition has a triad of multiple renal cysts, occipital encephalocele and polydactyly?
Meckel Gruber syndrome
What are the 2 most common RASopathy’s
NF1 and Noonan syndrome
What is an autosomal recessive disorder of euthyroid goitre and associated with senorineural hearing loss ? MOST common cause of syndromic hearing loss and accounts for >10% of hereditary deafness?
Pendred syndrome
autosomal dominant genetic abnormality and results from bilateral malformations of first and second branchial arches
Treacher Collins syndrome
extremely rare lethal form of congenital muscular dystrophy and almost always shows fetal hydrocephalus
Walker-Warburg syndrome (WWS), sometimes known as HARDE syndrome
What is the MOST common lethal genetic disease in caucasians?
CYSTIC FIBROSIS
MOST common infections seen in CF?
Burkholderia cepacia
Pseudomonas aeruginosa - biofilm
What are the findings of LEFT isomerism ?
polysplenia
azygous/hemizygous continuation of the IVC
bilateral HYPOarterial bronchi
Bilateral bilobed lungs
Bilateral pulmoanry/left atria
midline/transverse liver
intestinal malrotation
What are the findings of RIGHT isomerism ?
Asplenia
Severe Cyanotic CHD
Bilateral eparterial bronchi
Bilateral trilobed lungs
Bilateral right atria
Midline/transverse liver
interstinal malrotation
What is the MOST common brain malformation and the 3 subtypes
HOLOPROSENCEPHALY
Alobar
semilobar
lobar
Triad of
situs inversus
sinusitis/nasal polyps
bronchiectasis
Kartagener syndrome
primary defect is a retrognathic mandible which occurs at 7-11 weeks of gestation due to abnormal development of the first pharyngeal arch. Characterised by
micrognathia
glossoptosis
posterior cleft palate or high arched palate
Robin sequence
CHARGE syndrome stands for
If this is suspected patients should have what imaged?
Coloboma
Heart defects
Atresia Choanea
retarded growth
genital hypoplasia
ear abnormalities/deafness
CT temporal bones
MRI brain
complex congenital anomaly characterised by abnormalities of the ears, eyes and vertebrae.
Goldenhar syndrome
rare congenital condition characterised by the absence or underdevelopment of the nuclei of the abducens (CN VI) and facial nerve (CN VII).
Mobius syndrome
Unilateral absence of pectoralis major and minor muscles
Poland syndrome
rare congenital malformation characterised by the fusion of lower limb structures.
Sirenomelia
CREST syndrome stands for
CREST syndrome (also known as limited systemic sclerosis or limited scleroderma) is a variant of progressive systemic sclerosis (PSS) and stands for
C - calcinosis
R - Raynaud phenomenon
E - oesophageal dysmotility
S - sclerodactyly
T - telangiectasia
autoimmune connective tissue disorder characterised by multisystem fibrosis and soft tissue calcification
What are pathognomonic findings
Scleroderma, also known as systemic sclerosis
More common in females
hidebound bowel and dilatation of the distal 2/3rds of the eosophagus
Clinical manifestation depends on which systems are predominantly involved. It should be noted that the majority of patients 70-97% develop an arthropathy that mostly affects the fingers, wrists, and ankles 3,5. Oesophageal involvement is common, occurring in approximately 80% of patients 5. Although 90% of patients have pulmonary involvement histologically, only a minority are symptomatic
Serological markers for Scleroderma
MOST common ones that are positive
antinuclear antibodies (ANA): 35-96%
anti-Scl-70 antibodies: 30-70% (particularly in diffuse disease)
rheumatoid factor- positive in 30-40%
anti-centromere antibodies: 20-40% (particularly in limited disease)
ESR
What systems are commonly involved in Scleroderma?
MSK - acro-osteolysis
subcutaneous and periarticular calcs
GI - eosophagus 80%
- Small bowel (duodenum) 80%
- LB 40%
- Stomach - rare
Renal - 25% - HTN and acute renal failure
What does PHACE syndrome stand for
P: posterior fossa malformations (e.g. Dandy-Walker malformation)
H: haemangiomas
A: arterial anomalies
C: coarctation of the aorta and cardiac anomalies
E: eye (ocular) anomalies
What does VACTERL stand for ?
V: vertebral anomalies
hemivertebrae
congenital scoliosis
caudal regression
spina bifida
A: anorectal anomalies
anal atresia
C: cardiac anomalies; cleft lip
TE: tracheo-oesophageal fistula +/- oesophageal atresia
R: renal anomalies; radial ray anomalies
L: limb anomalies
polydactyly
oligodactyly
