Cardio - Boards Exam

Congenital Heart Defect

CHD occurs in 0.8% of live births → Central Septal Defects most common

• Multifactorial 70%:

  • Empiric CHD Recurrence Risk 3-5% - Decreased with maternal folate intake

• Genetic 25%:

  • Chromosomal and Single Gene

• Environmental/Teratogenic 5%

  • Maternal Alcohol, Diabetes, ***PKU***, 1st trimester fever

    • SSRI → Persistent Pulmonary Hypertension

    • NSAID → Patent Ductos Arteriosus Closure

    • Lithium → Epstein’s Anomaly

Noonan Syndrome: Cardinal Features

Overlap with Turners Syndrome → Can rule out Turners if MALE

Generally NORMAL LIFE EXPECTANCY

• Cardiac

  • ****Pulmonary Valve Stenosis/Dysplasia*****

  • Hypertrophic Cardiomyopathy

• Dysmorphic features

  • Down slanting eyes w/ Ptosis

  • ***Webbed Neck**** → TURNER LIKE

  • ***Shield Chest*** → TURNER LIKE

• Mild ID → can be normal intelligence

• Hematologic:

  • Easy bruising / Excessive bleeding (epistaxis)

• MALES → Cryptorchidism (undescended testicles), bruising fertility, delayed puberty

PRENATAL FINDINGS

• Increased Nuchal Translucency

• Cystic Hygroma

Noonan Syndrome: Etiology

A RASopathy→ Mutation of RAS/MAPK signaling pathway

• PTPN11 50%*** (P.Valve + Short Stature + Bleeding)

• SOS1 10-15%

• RAF1 5-10% (HCM)

• RIT1 5-10% (HCM w/ pre-natal edem/hydrops)

• KRAS <5%

• NRAS rare

Inheritance

• Autosomal Dominant

  • 60% De Novo

  • 40% Inherited

Prenatal Findings (NT or Cystic Hygroma) w/ a NORMAL CHROMSOMAL ANALYSIS → THINK NOONAN SYNDOMRE

CHARGE Syndrome: Clinical Features

Clinical Features is VARIABLE and can be mild to severe and encompass MANY organ systems

Life Expectancy CAN BE DECREASED

• Coloboma: piece of iris missing, pupil too big and misshapen

• Heart Defects: wide variety (70-80%)

  • ToF, VSD, ASD, Aortic Arch, PDA,

• Atresia of the Choanae: back of nasal passage blocked

• Restricted Growth/development:

• Genital Abnormalities: (particularly males) hypogonadism, delayed puberty

• Ear Abnormalities: Hearing loss (Conductive AND Senso-neural), external ear abnormality

  • ****HEARING LOSS****

  • POOR BLANCE (hypoplastic or absent semi-circular canals)

Additional features discovered after gene was identified

• Brain

  • Seizures

  • Abnormalities (Dandy walker, microcephaly,

  • ****Cranial Nerve Abnormalities**** → contributes to hearing loss

• Endocrine Dysfunction

CHARGE Syndrome: Etiology

Gene: CHD7 (important for Neural Crest Cell migration)

Inheritance

• Autosomal Dominant

  • 90% De Novo

  • 10% Inherited

• Can be inherited from a mildy affect parent that didn’t know they had it

Marfan Syndrome: Clinical Features

• ****Aortic Root Dilation****

  • May progress to aneurysm, dissection, rupture → LEADING CAUSE OF DEATH

  • untreated = shortened life expectant

• Eye

  • ***Ectopia Lentis*** → UPWARD DISPLACMENT (vs. downward for Homocysturia)

• Skeletal

  • Tall stature

  • Long, slender fingers

  • Pectus Excavatum / carinatum***

  • Scoliosis

  • Joint hypermobility***

• Pulmonary

  • ****Pneumothorax****

• Spine

  • ***Dura Ectasia*** (weakening or enlarging of membrane around spinal cord)

Treatment

• Echocardiogram 2 times a year

• Beta Blockers + Angiotensin receptor blockers (Losartan) decreased progression of Aortic Wall weakening

Marfan Syndrome: Etiology

Gene: FBN1 (important for connective tissue)

Inheritance

• Autosomal Dominant

  • 75% Inherited

  • 25 De Novo

  • ****PATERNAL AGE EFFECT****

Marfan-Like Syndrome

Conditions that have Marfanoid features PLUS additional signs:

• Loeys-Dietz (TGFBR1 + TGFBR2): Abnormal Palate and DIFFUE aneurysm (throughout the body)

• Homocystinuria (CBS): Mental retardation and High Homocysteine blood levels

• Beals syndrome (FBN2): contracture and crumpled ears

• Multiple Endocrine Neoplasia (MEN) 2A and 2B (RET): Pheocytocytoma and Medullary Thyroid cancer

Ehlers-Danlos Syndromes: Overview

Group of hereditary connective tissue disorder caused by collagen gene mutation and sharing common cardinal features:

• Joint hypermobility: joint flexibility, joint dislocation

• Skin hyperextensibility and fragility: easy bruising, slow healing

• Connective tissue fragility

  • Hernias

  • Valvular hear disease

  • Preterm delivery

  • Bowel dilation/rupture

3 main types

• Hypermobile EDS

• Classical EDS

• Vascular EDS

Elhers Danlos Syndrome - Hypermobile

Gene: NO SINGLE GENE has been identified DESPITE being the most commo form of EDS (80-90% of EDS cases)

Inheritance

• Autosomal dominant

• Variable expressivity

• Diagnosis is made CLINICALLY

Clinical Features

mostly joint flexibility with MINIMAL SKIN FINDINGS

Normal life expectancy

• Musculoskeletal

  • Joint hypermobility - chronic joint pain, dislocations/subluxation

  • Flat feet

• Skin

  • NO SEVERE FRAGILITY

  • mildly stretchy

  • easy bruising (wound healing not affected)

• Other

  • Chronic fatigue

  • GI discomfort (IBS)

  • Autonomic dysfunction (common)

    • Orthostatic intolerance

    • Postural orthostatic tach cardia syndrome (POTS)

Elhers Danlos Syndrome - Classical

Gene: COL5A1, COL5A2 (regulates collagen type V)

Inheritance

• Autosomal Dominant

  • Inherited 50%

  • De Novo 50%

Clinical Features

Skin findings are MUCH more pronounced than hEDS

Life expectancy normal

• Musculoskeletal (less severe than hEDS)

  • Joint hypermobility

  • recurrent dislocations

  • Chronic joint pain

• Skin (way more pronounced than hEDS)

  • EXTREMELY stretchy

  • Fragile

  • ****POOR WOUND HEALING****

  • ****EASY BLEEDING****

  • ****SCARS**** (knees, elbows, forehead, chin)

• Cardiac (not as bad as vEDS)

  • Mild Aortic Root Dilation

  • Mild mitral valve prolapse

• Other

  • Organ prolapse and hernia

Ehlers Danlos Syndrome - Vascular

Gene: COL3A1 (encodes type III collagen)

Inheritance

• Autosomal dominant

  • Inherited 50%

  • De Novo 50%

Clinical features

Mostly artery, intestinal and uterine fragility

Life expectancy REDUCED (vascular dissection/rupture)

• Vascular

  • Arterial aneurysm/ dissection/ rupture (spontaneous)

    • Carotid, Iliac, Mesentric, RENAL, Brain

    • Aorta (NOT AS MUCH AS MARFANS)****

• GI

  • Spontaneous bowel perforation (rupture

• Uterine

  • Pregnancy risk → uterine rupture

• Muscoskeletal

  • mild hypermobility - FINGERS ONLY

• Skin

  • NOT super stretchy (unlike hEDS and cEDS)

  • *****thin/ translucent skin*****

  • Easy bruising

• Face

  • Aged appearance

  • Thin nose, lips

  • narrow face

  • small chin

Management

• No contact sports, working out, unnecessary surgery

• PREGNACY is HIGH RISK

Familial Hypertrophic Cardiomyopathy: Overview

Genes: MYBPC3 (50%), MYH7(40%)

• MYBPC3: later onset, slower progression less severe

• MYH7: earlier onset, greater penetrance for young, more severe

Inheritance

• Autosomal Dominant

  • Inherited 90%

  • De Novo 10%

• ***AGE DEPENDENT PENETRANCE***

  • No symptoms as infant + child

  • Early and Late Adulthood features can emerge

  • Some carriers NEVER show phenotype

Clinical Features

• Left Ventricle Hypertrophy (>15mm wall thickness)

  • Shortness of breath

  • Palpitations

  • Exercise intolerance

  • Passing out (syncope

  • SUDDEN CARDIAC DEATH (can be first manifestation)

• Left ventricular outflow tract obstruction → HEART MURMUR

• Atrial Fibrillation → heart failure and STROKE

Familial Hypertrophic Cardiomyopathy: Recommendations

Diagnosis

• Physical exam → heart murmur check

• Electrocardiogram

  • deep Q waves

  • T-wave inversion

  • ventricular ectopy

• Echocardiogram

Treatments

• Beta blockers (1st line) (slow heart rate)

• Calcium channel blockers (slow heart rate)

• Surgical

  • Implantable Cardioverter-Defibrillator

  • Septal myectomy

  • Alcohol septal ablation

Family Recommendations

• even if testing negative, PERDIOIC CLINCIAL SCREENING still recommended since familial cause of HCM remain unidentified

Syndromic HCM

• Noonan Syndrome

  • as well as other RASopathies

• Pompe Syndrome

• Friedreich’s Ataxia

• Fabray Disease

Familial Dilated Cardiomyopathy: Overview

Gene: TTN (30%), *LMNA* (10%), *MYH7* (5-10%) → many other genes

• LMNA: electrical disease before pump failure → AV block/Sinus node dysfunction BEFORE left-ventricle dysfunction develops → ****MUCH HIGHER RISK OF SCD than TTN****

Inheritance

• Autosomal Dominant

  • Mostly inherited

  • LMNA: 10-30% De Novo Rate

• ***AGE RELATED PENETRANCE***

  • Incomplete Penetrance

Clinical Features

• Dilated Cardiomyopathy

  • Fatigue

  • Shortness of breath (ESCPIALLY LYING FLAT)

  • Exercise intolerance

  • Palpitations

  • Passing out (syncope)

• Heart Failure (progressive reduction of ejection fraction)

• Arrythmias

  • Atrial + ventricular fibrillation

• SUDDEN CARDIAC DEATH

  • ***LMNA ESPECILLAY**

Familial Dilated Cardiomyopathy: Recomendations