>45% of this type of LQTS

63% of patients have cardiac events, typically triggered by exercise or emotional stress

Of Roman Ward syndromes, syncopy is the common in this one

Broad-based T waves on EKG

Mutation in KCNQ1 and KCNE1

Mutations lead to abnormal IKs potassium channel function

~40% of patients of this type of LQTS

46% have events usually triggered by exercise, emotional stress, or sleep

Events can, but not always, be triggered during sleep

Bifid T waves

Mutation in KCNH2 (HERG) and KCNE2

Mutations lead to abnormal IKr potassium channel function

Less that 10% of this type LQTS

18% have cardiac events

Long ST, small or biphasic T waves

Events triggered during sleep

Can only have a mutation in SCN5A, the sodium channel gene that causes abnormal INa channel function

Death is the first sign in 10-15%

Risk of sudden death from birth to age 40 is ~4% in each type

Genetic testing available for all 5 genes

75% of patients have a detectable mutation

Most common age of presentation is pre-teen years to 20s

Incidence is 1 in 7,000 in most populations

QT prolongation, T wave abnormalities, tachyarrhythmias including TdP

Most common symptom of this SYNDROME is syncope

50-70% of individuals with disease causing mutations have symptoms

Autosomal Recessive ONLY

Incidence is 1 to 6 per million

Deaf

Very long QTc

50% die by 15 years old if untreated

Homozygous for KCNQ1 (>90%)

Homozygous for KCNE1 (less than 10%)

Up to 50% are de novo mutations

Episodic flaccid muscle weakness (periodic paralysis)

Can have syndactyly, clinadactyly (5th finger toward 4th), short stature, scoliosis, hypertelorism, low set ears, and micrognathia

Mutation in KCNJ2

Mutation in inward rectifier potassium channel 2 protein

~60% have detectable mutation

Nearly all cases are new mutations

Syndactyly of fingers 2 through 5 and toes 2 and 3

Can have structural cardiac defects, HCM, dysmorphic facies, and neurologic abnormalities

Mutation in G406R

Affects calcium channel gene

Affects CACNA1C

Very rare disorder that causes LQTS

Rare disorder with high mortality in childhood

Prevalance is 1 in 10,000

Mean age of onset is 7 to 9

Syncope during exercise or acute emotion (besides RW)

Diagnosed by reprodible ventricular arrhythmias during stress testing

Heterozygous mutation in RARY2

Heterozygous mutation in 50 to 55% of patients

Homozygous mutation in 1 to 2%

Homozygous mutation in CASQ2

Incidence ranges from 5 to 66 per 10,000 in well sudied Asian populations

Common in Asian populations, less common in Europe and US

May be cause of 20% of sudden deaths in people with a normal looking heart

ST elevation in right precordial leads (V1 to V3)

RBBB in some patients

Events can be triggered during sleep (not RW)

EKG can be normal

Mutation in SCN5A (in some patients)

Only 20 to 25% of patients have a detectable mutation

Males are more commonly affected (8:1)

Average onset is 40 years

Range of onset is 2 days to 84 years

Presents with ventricular arrhythmias, at times lethal, particularly in the young and athletes

Mean age of diagnosis is 31 years, range 4 to 64 years

Autosomal dominant and recessive forms exist

Incidence of dominant form ranges from 6 in 10,000 to 4 in 1,000 in some areas

Most common cause of sudden cardiac death in young Italians

~17% of sudden death among young Americans

2 of these needed for diagnosis

4 needed for diagnosis

1 needed if have 2 of the other kind

Criteria: Severe RV dilation and reduction of RV function with mild or no LV impairment

Criteria: Localized RV aneurysms

Criteria: Severe segmental dilation of the RV

Criteria: Fibrofatty replacement of the myocardium on endomyocardial biopsy

Criteria: Epsilon waves

Criteria: Localized prolongation (>110 ms) of the QRS in the right precordial leads (V1 to V3)

Criteria: Positive family history, confirmed at autopsy or surgery

2 needed if have one of the other kind

Criteria: Mild global RV dilation and / or EF reduction with nomal LV

Criteria: Mild segmental dilation of the RV

Criteria: Regional RV hypokinesis

Criteria: Inverted T waves in right precordial leads (V2 and V3) (age >12 years) in absence of RBBB

Criteria: Frequent PVCs (>1,000 in 24 hours)

Criteria: LBBB-type V tach

Criteria: Family history of premature sudden death suspected to be caused by ARVD

Criteria: Positive family history of ARVD based on Task Force criteria

Parents and siblings should be screened by MRI or echo, EKG or molecular testing, if a mutation has been identified regardless if they have symptoms

Incomplete penetrance but asymptomatic individuals may still be at risk for later difficulties

Percentage of de novo mutations is unknown

Rare, also known as Naxos disease

Associated with dermatologic findings

Woolly hair

Palmoplantar keratoderma

Homozygous mutation in plakoglobulin

Mutation in gene affecting desmosomes and adherens junctions

Autosomal dominant, incidence ~1 in 500

Most common cause of death in youth in the US

~36% of sudden death in athletes under 35

Sudden death usually due to arrhytmias but patients may also die of stroke or progressive heart failure

Can result from mutation in 1 of 11 genes

Death can also be caused by stroke or progressive heart failure

Tentative association between ACE variants and extent of this disease

Modifier genes may affect expression of mutations

Is a disorder of the sarcomere

Some genotype-phenotype correlations have been identified but the impact of these on current therapy is unclear

Accurate classification if at-risk family members is the primary advantage of genetic testing in individual with a clinical diagnosis

Mutation in MYH7, presents in first 2 decades

MYH7 (B-myosin heavy chain gene) - most common gene mutation, ~35%

MYBP3 (myosin binding protein c, cardiac): occurs during 5th or 6th decades, 15% of gene causing mutations

TNNT (troponin 2, cardiac): less hypertrophy, more death, 15% of gene mutations

Resembles familial HCM, but distinguished by electrophysiological abnormalities

Can particularly be associated with ventricular preexcitation

2 types of dominant forms exist

What syndrome can have a lysosomal form

Mutation in LAMP2 (lysosomal associated membrane protein 2)

Cytoplasmic form is part of what syndrome?

Has cytoplasmic form with mutation in PRKAG2 (AMP-acitivated proten kinase g2)

Substantial proportion of CM not from sarcomere mutations

Mutation in LAMP2 (lysosomal associated membrane protein 2)

X-linked dominant subtype

Earlier age of onset and more severe course in males

Severe LV hypertophy and variable muscle weakness

Progressive conduction system defects, WPW, mentral retardation

This syndrome can have WPW

This subtype has a prognosis that is much worse than HCM

Elevated CK: X-linked dominant in this subtype

Patients who present in adolescense often die by early adulthood

Offspring of affected female have 50% chance of being affected

In affected males: daughters affected, sons not affected

Autosomal dominant, cytoplasmic subtype

Increased glycogen producation causes glycogen accumulation throughout the cardiomyocyte in this subtype

Compatible with long survival although pacemakers and aggressive treatment of arrhythmias may be required

25-50% of cases are familial

Autosomal dominant form has 2 broad categories: with and without conduction system disease

No specific clinical features distinguish between familial and nonfamilial forms

Younger patients are more likely to have familial disease

Elevated CK: X-linked recessive

Autosomal dominant form is most common

X-linked recessive form can occur

Autosomal recessive one of 4 forms

Mitochondreal inheritance form can occur

The autosomal dominant form accounts for ~90% of this disorder

17 autosomal dominant genes identified

None of the autosomal dominant genes account for more than 5 to 10% of disorder

X-linked form causes 5 to 10%

X-linked mutations: dystrophin and G4.5 / tafazzin

X-linked recessive mutation in dystrophin that also causes Duchenne and Becker MD

X-linked recessive mutation G4.5 / tafazzin also causes Barth syndrome and this disease +/- non-compaction

The autosomal recessive form of this if more like to occur in certain ethnic groups or consanguinity and is very rare

The only gene linked to the AR form of this is troponin I

Mitochondrial point mutations and deletions; cause multiorgan system disease

Mitochondrial form of this is part of