HG 400B Final

Brugada primary gene(s)

SCN5A (LOF)

Brugada inheritance

AD

Brugada symptoms

Syncope or nocturnal agonal respiration; sudden unexplained nocturnal death syndrome

Brugada clinical test

EKG

Friedreich’s Ataxia gene(s)

FXN (GAA trinucleotide repeat >66)

Friedreich’s Ataxia inheritance

AR

Friedreich’s Ataxia symptoms

Progressive limb and gait ataxia before 25 yo, absent tendon reflexes in lower extremities, dysarthria, areflexia, pyramidal weakness of legs, extensor plantar responses, and distal loss of joint position and vibration sense; scoliosis, pes cavus, optic nerve atrophy, HCM, DM; (unique: Ataxia with HCM, DM, scoliosis (young))

SMA gene(s)

SMN1 (del in exon 7)

SMA inheritance

AR

SMA symptoms

Arthrogryposis multiplex congenita, peripheral nerve hypomyelination; muscle weakness, tongue fasciculations, absent DTRs

SMA clinical testing

EMG, muscle bx

Fragile X gene(s)

FMR1 (CGG trinucleotide repeat >200)

Fragile X inheritance

XLR

Fragile X symptoms in non-carriers

Delayed motor and verbal development, intellectual delay, autism, prominent jaw and forehead, large testes

Fragile X symptoms in carrier females

Premature ovarian failure, tremor ataxia (late onset)

Brugada genetic test

SCN5A gene sequencing

Friedreich’s Ataxia genetic test

FXN sequence analysis/GAA triplet repeat

SMA genetic test

Targeted mutation analysis/SMN1 sequencing

Fragile X genetic test

PCR for CGG repeat number

Jervell-Lange-Nielsen Syndrome gene(s)

KCNQ1 and KCNE1

Jervell-Lange-Nielsen Syndrome inheritance

AR

Jervell-Lange-Nielsen Syndrome symptoms

Sensio-neural hearing loss and Long QT syndrome (type 2); at risk for arrhythmia, syncope, and sudden death

Jervell-Lange-Nielsen Syndrome genetic test

KCNQ1 and KCNE1 gene sequencing

EDS Vascular gene(s)

COL31A

EDS Vascular inheritance

AD

EDS Vascular symptoms

Arterial rupture, intestinal rupture, uterine rupture during pregnancy, and keratoconus

EDS Vascular genetic test

COL3A1 gene sequencing

Marfan syndrome gene(s)

FBN1

Marfan syndrome inheritance

AD

Marfan syndrome symptoms

Dilation of aorta, pectus, long arms, scoliosis, pes planus, high arched palate, reduced elbow extension, ectopia lentis, dural ectasia

Marfan syndrome clinical test

Echo, CT/MRI

Marfan syndrome genetic test

FBN1 gene sequencing

Long QT 1 triggers

Exercise, sudden emotion

Long QT 2 triggers

Sleep, exercise, emotion

Long QT 3 triggers

Sleep

Brugada triggers

Sleep, fever

Catecholaminergic polymorphic ventricular tachycardia (CPVT) gene(s) and inheritance(s)

AD GOF mutations at RYR2; rarely LOF AR mutations at CASQ2

CPVT symptoms

Childhood-onset arrhythmia triggered by exercise or emotion

CPVT clinical test

Exercise stress test can induce arrythmia/v-tach

LQT1 gene

KVLQT1

LQT2 gene

HERG

LQT3 gene

SCN5A (GOF)

Nonsyndromic Hypertrophic Cardiomyopathy gene(s)

MYH7, MYBPC3

Nonsyndromic Hypertrophic Cardiomyopathy inheritance

AD

Nonsyndromic Hypertrophic Cardiomyopathy symptoms

Exertional dyspnea, chest pain, presyncope, and asymmetric LV wall thickening without dilation; can cause sudden death/cardiac arrest; MYH7 is associated with the earliest onset

Nonsyndromic Hypertrophic Cardiomyopathy clinical test

Echo/CMR/EKG

LQTS clinical test

EKG

F-TAAD clinical test

Echo/CT/MRI

Fabry gene(s)

GLA

Fabry inheritance

XLR

Fabry symptoms

Angiokeratomas, episodic severe extremity pain, hypohidrosis, corneal/lenticular opacity, abdominal pain, and renal insufficiency

Familial hypercholesterolemia gene(s)

LDLR, APOB, LDLRAP1, PCSK9

Familial hypercholesterolemia inheritance

AD

F-TAAD gene(s)

ACTA2, LOX, MYH11