Genetics Flashcards
PKP2 genetic mutation is associated with..
Arrythmogenic cardiomyopathy (ARVC)
Most common inheritance pattern of dilated CM
Autosomal dominant
What is Barth Syndrome?
- Inheritance pattern
- Findings
Inheritance- X linked recessive, mutation in TAZ gene
Findings: Dilated CM or non-compaction CM
Other findings: Hypotonia, short stature, proximal muscle weakness, neutropenia, abnroaml 3-methylglutaconic aciduria
What two genes account for 75% of familial sarcomeric HCM?
MHY7 and MYBPC3
Most common RASopathy associated with HCM
Noonan syndrome
Beside HCM, what other CHD can patients with Noonan syndrome develop?
Pulmonic stenosis
Name 3 genes that are associated with RASopathies
PTPN11
RAF1
RIT1
Can think of Josh saying “quit it with the rit raf!!”
Most common mutation associated with Noonan
PTPN11
Most common gene mutation associated with inherited DCM
TTN (5-25%)
Inheritance pattern of dystrophinopathies
Mostly X linked
Describe the etiology of the different presentations of Duchenne vs Becker DCM
Duchenne: absence of the dystrophin gene
Becker: some dystrophin gene, short and partial function
Emery-Dreifuss MD: What genes are associated?
EMD and FHL-1 (x linked)
LMNA (AR and AD)
Proteins involved in the nuclear membrane of the myocytes
What clinical features are present with Emery-Driefuss MD?
Cardiac: DCM > HCM, conduction abnormalities and arrhythmia
Non-cardiac: Contractures and progressive weakness/wasting
Gene associated with increased risk of SCD in patients with Limb-Girdle MD?
DES mutations
What three genes in muscular dystrophies are associated with increased arrhythmia risk?
EMD, LMNA, and DES
What are the clinical findings of 1p36 deletion syndrome?
Small head, deep eyes, straight eyebrows, midface hypoplasia, developmental delay
+ DCM, LVNC and a slew of other CHD - ASD. VSD, PDA, PS, BAV, etc.
What two syndromes are associated with LV non compaction CM?
Barth’s (also DCM)
1p36 microdeletion (also DCM)
What is the inheritance pattern of most inborn errors of metabolism?
AR
Name two mitochondrial inborn errors of metabolism
MELAS : Mitochondiral encephalopathy, lactic acidosis and stroke
Kearns-Sayre: Cranial and opthalmologic
What is the clinical presentation of Kearns Sayre?
(mitochondrial deletion)
Age < 20
Progressive opthalmoplegia
Pigmentary retinopathy
Progressive heart block 2/2 degeneration of the conduction system
What is a common presentation of a fatty acid oxidation defect and what is an example?
Acute decompensation after fasting
Hypoglycemia, metabolism acidosis, hyperammonia, abnormal acyl carnitine profile
Example: CPT2
Pompe disease: What is the official name? What gene is involved?
Official name: glycogen storage disease II
Gene involved: GAA
Dannon disease: What gene is involved? How can you differentiate clinically from Pompe?
LAMP2
Will have normal values of alpha acid gluconidase levels
Why. is the PR interval important in pompe?
Progressive accumulation of glycogen in the conduction system > increased PR > increased risk of SCD
Name 2 lipid storage diseases associated with CM
Gaucher and Fabry
Describe the cardiovascular subtype of gaucher
glucocerebrosidase deficiency
Calcification of mitral and aortic valve
mutation in GBA
Describe clinical manifestations of Fabry
x-linked, GLA mutation
Severe extremity pain
Corneal involvement
Renal failure
Conduction abnormalities + HCM
Name the syndrome: coarse facial features, short, severe HSM, thickened leaflets resulting in regurg
mucopolysaccharide storage dx
Hurler (AR) and hunter (X linked)
Hunter does not have corneal clouding
CAVC, low tone,
upslanting palpebral
fissures, advanced
maternal age
T21
Polyvalvar disease,
clenched hands with
overlapping fingers,
nail hypoplasia, low
set ears, small mouth
Edward syndrome (T18)
Orofacial clefts,
microphthalmia/anoph
thalmia, postaxial
polydactyly,
holoproscencephaly
Trisomy 13 (Patau)
Inheritance pattern of the Trisomies
AD although the VAST majority are denovo mutations
Female with short stature, left-sided lesions
Turner syndrome
What cardiac lesions are seen with Turner syndrome?
Left-sided lesions
- CoA
- BAV/AS
- HLHS
- mitral valve prolapse
- aortic root dilation/dissection
Pulmonary vein anomalies
Prolonged QTc
Interrupted aortic arch type B, conotruncal
defects, absent thymus, hypocalcemia
DiGeorge (22q11)
Supravalvar aortic stenosis, stellate
irises, short stature, hoarse voice, unique cognitive profile
Williams syndrome
Cardiac lesions seen in Williams syndrome
Supravalvar AS
Supravalvar PS
Peripheral pulmonary artery stenosis
Arteriopathy
Syndrome with HLHS
Jacobsen syndrome
What is the best genetic testing for STRUCTURAL VARIATION / COPY NUMBER VARIATION / MICRODELETION SYNDROMES
Chromosomal microarray
Cutis aplasia
Syndrome with HLHS
Adams Oliver syndrome
What is the best genetic testing for SINGLE GENE DISORDERS?
Gene sequencing - either targeted or whole genome
PPS, triangular faces, butterfly vertebrae, cholestasis
Alagille syndrome
What gene is mutated in Alagille syndrome?
JAG1
Short stature, developmental delay,
ear anomalies, coloboma, tetralogy of
Fallot
CHARGE syndrome
What gene is mutated in CHARGE syndrome?
CHD7
Synophrys
Long curled eyelashes
VSD, ASD, PS
Cornelia De Lange syndrome
Short stature, dental anomalies,
polydactyly, common atrium
Ellis van Creveld (EVC mutations, AR)
Upper extremity anomaly, absent
thumb, common atrium, heart block,
affected parent
Holt Oram
What cardiac finding needs to be monitored in Holt Oram disease?
Progressive heart block
What gene is mutated in Holt Oram disease?
TBX5
Wide palpebral fissures with
eversion of the lateral third of
the lower eyelid
Arched, broad eyebrows, left sided lesions
Kabuki syndrome
What cardiac lesions can you see with Kabuki syndrome?
LSL: CoA, BAV, HLHS
VSD
TOF
TGA
Broad thumbs, “grimacing” smile
Intellectual disability PDA or septal fect
Rubinstein-Taybi
Pulmonic stenosis
(thick/dysplastic
valve), HCM, short
stature, neck
webbing, pectus, low
set ears
Noonan
Short stature, loose skin, multifocal atrial
tachycardia
Costello syndrome
Multiple café au lait spots, axillary and inguinal freckling, Cutaneous neurofibromas
Iris Lisch nodues, CoA, PS
Neurofibromatosis 1
(no intracardiac masses)
Gene mutation in Marfans
FBN1 (AD)
Tall thin habitus with long armspan,
scoliosis, thick glasses, pectus, aortic
root dilation, mitral valve prolapse,
ectopia lentis
Marfan
Gene mutations (2) in Loeys Dietz
TGFBR1
TGFBR2
Arterial aneurysms, tortuosity, aortic root
dilation, widely spaced eyes, bifid
uvula, pectus, BAV, PDA, club foot
Loeys-Dietz
Marfan’s appearance, Crumpled ears, joint
contractures at birth, scoliosis, aortic root
dilation
Congenital Contractural
Arachnodactyly (Beals)- FBN2
TV prolapse, MV prolapse
AoR dilation (not
progressive) Arterial rupture (very
rare)
EDS classic
What gene is involved in Ehler Danlos?
COL
Dextrocardia, bronchiectasis, nasal
polyps
Kartagener, Primary ciliary dyskinesia
Inheritance of Kartagner’s disease
AR
Cardiac rhabdomyoma, skin
findings, infantile
spasms
Tuberous Sclerosis
Williams syndrome has a mutation in what chromosome?
7q11
Cru-de-chat syndrome is caused by what?
Deletion on chromosome 5
5p- syndrome
What trisomy has the highest rate of CHD?
T18 - 95% chance of CHD
What connective tissue diseases has the risk of aortic dissection?
Marfans and LD
ED does not
What condition can appear like Marfans but is associated with intellectual delay?
Autosomal recessive homocystienuria
What cardiac lesions is maternal PKU associated with?
Primarily left sided lesions - HLHS, coarctation
