Session 7 — CHD Associated With Genetic Disorders, Maternal Teratogens & Syndromes

How common is congenital heart disease, and list the 6 indications for evaluating CHD.

• About 8 per 1,000 live births

• About 35,000–40,000 children per year

Indications:

1. Family history

2. Maternal teratogen exposure

3. Chromosomal abnormalities

4. Syndrome inheritance

5. Maternal conditions/extracardiac anomalies

6. Rhythm abnormalities

What is the #1 reason for a pediatric echo, and what is the fetal CHD risk based on family history?

Family history of CHD is the #1 reason.

• Mother has CHD → 10–12%

• One sibling has CHD → 2–4%

• More than one sibling → 10%

• Father has CHD → 1–3%

If CHD reoccurs in a family, does it have to be the same heart defect?

No. The recurrent CHD is not limited to the same type of defect.

What is a maternal condition versus a maternal teratogen?

• Maternal condition: A condition the mother already has, such as hypertension

• Maternal teratogen: Exposure to a drug or substance capable of causing birth defects

Both can increase the risk of CHD

What determines the risk from maternal teratogen exposure?

• Length of exposure

• Type of exposure

• Specific substance involved

Are drugs the only things that can have teratogenic effects?

No. Disease processes or external influences such as diabetes and obesity may also have teratogenic effects on the fetus

What CHDs are associated with maternal rubella and maternal diabetes?

• Rubella — 50%: Branch pulmonary stenosis and PDA

• Diabetes — 18%: d-TGA, truncus arteriosus, and single ventricles

What CHDs are associated with maternal PKU and maternal autoimmune disease/SLE?

• PKU — ~20%: TOF and coarctation of the aorta

• Maternal autoimmune disease/SLE — 20–40%: Complete heart block

What CHDs are associated with maternal alcohol abuse and maternal infection?

• Alcohol abuse — 50%: VSDs and ASDs

• Maternal infection: Dilated or hypertrophic cardiomyopathies

What is the CHD risk and associated defects with trimethadione and hydantoin?

Trimethadione — ~50%:

• VSD

• ASD

• PDA

• AS

• PS

• TOF

Hydantoin — 10%:

• VSD

• ASD

• PS

What defects are associated with thalidomide and lithium?

Thalidomide — <5%:

• TOF

• ASD

• Truncus arteriosus

Lithium — 3%:

• Ebstein anomaly

• Truncus

• ASD

• MV atresia

• Dextrocardia

What is retinoic acid associated with?

50% risk with:

1. TGA

2. TOF

3. VSD

4. Interrupted aortic arch — IAA

What are ACE inhibitors and SSRIs associated with?

• ACE inhibitors — 5–10%: VSD and ASD

• SSRIs — up to 74%: PPHTN

What are barbiturates, vitamin D, and indomethacin associated with?

• Barbiturates: IAA and aortic arch coarctation

• Vitamin D: Supravalvular aortic stenosis

• Indomethacin — 50%: Premature ductal closure

What are chromosomal abnormalities, and how can they affect the heart?

They are abnormalities at the root of many inherited diseases and traits that can cause birth defects and congenital conditions.

The type of heart defect depends on the specific chromosomal abnormality.

What 2 types of chromosomal abnormalities are listed?

• Numerical abnormalities — change the number of chromosomes

• Structural abnormalities — change chromosome structure

What is aneuploidy, monosomy, and trisomy?

• Aneuploidy: Abnormal number of chromosomes

• Monosomy: Missing one chromosome from a pair

• Trisomy: More than 2 copies of a chromosome in a pair

What are examples of trisomy and monosomy?

• Down syndrome: Trisomy 21 — extra chromosome 21

• Turner syndrome: Monosomy — only one X sex chromosome

List the 3 cardiac defects associated with Alagille syndrome and its major feature.

Cardiac defects:

1. Pulmonary stenosis

2. ASD

3. VSD

Major feature: Liver damage from bile-duct abnormalities, which may cause jaundice.

What physical features are listed for Alagille syndrome?

• Xanthomas

• Triangular face

• High forehead

• Deep-set eyes

• Pointed chin

• Saddle/straight nose with bulbous tip

What cardiac defects and major physical feature are associated with Apert syndrome?

• VSD

• Tetralogy of Fallot

• Cranial deformities

How often does Cat Eye syndrome have a cardiac defect, and list the 4 defects given.

About 40%.

1. TAPVR

2. VSD

3. ASD

4. TOF

What chromosomal abnormality and characteristic eye defect occur with Cat Eye syndrome?

• Partial trisomy 22

• Coloboma — cleft/gap in the iris below the pupil

How often does CHARGE syndrome involve heart defects, and list the 4 most common defects.

75–85% have heart defects.

1. TOF — 33%

2. VSD

3. AV canal defect

4. Aortic arch anomalies

What cardiac defects and major features are associated with Cri Du Chat syndrome?

Cardiac defects:

• VSD

• PDA

• TOF

Features:

• High-pitched cat-like cry

• Intellectual/developmental delay

• Small head and moon-shaped face

What 2 cardiac findings are associated with Friedreich ataxia?

• Hypertrophic cardiomyopathy

• Pulmonary stenosis

What system does Friedreich ataxia mainly damage, and when do symptoms usually begin?

It damages the nervous system, including the spinal cord and nerves controlling movement.

Symptoms usually begin between 5–15 years old

How often are heart defects seen in Goldenhar syndrome, and what heart defects are commonly associated?

• 5–58% have heart defects

• Septal defects

• Conotruncal defects such as TOF

• Situs inversus and looping defects may also occur

What major physical abnormality is associated with Goldenhar syndrome?

Hemifacial microsomia — underdevelopment of the bones and muscles on one side of the face.

What cardiac abnormality is associated with Kearns-Sayre syndrome?

Conduction defects such as AV block.

How often does Klippel-Feil syndrome have cardiac disease, and what is the most common defect?

• Cardiac disease occurs in 4.2–14%

• VSD is most common

• Coarctation may also occur

What is the major structural feature of Klippel-Feil syndrome?

Congenital fusion of 2 or more cervical spinal bones, causing:

• Short neck

• Low hairline

• Limited range of motion

What cardiac finding is associated with Klinefelter syndrome, and what chromosomal abnormality causes the syndrome?

• MVP occurs in 55%

• Occurs in males with an extra X chromosome

What 2 heart defects define Lutembacher syndrome?

• Congenital ASD

• Acquired, often rheumatic, mitral stenosis

List the 4 major cardiovascular findings/symptoms of Lutembacher syndrome.

1. RV overload/right-sided heart failure

2. Palpitations and future AF from biatrial dilation

3. Pulmonary congestion

4. Loud S1 and wide fixed splitting of S2

What is the major cardiac defect associated with Mowat-Wilson syndrome?

Pulmonary artery sling

How common are heart defects in Noonan syndrome, and list the 5 cardiac defects given.

65% have heart defects.

1. Pulmonary stenosis

2. VSD

3. ASD

4. Interrupted aortic arch

5. Hypertrophic cardiomyopathy

List the 5 cardinal features of Noonan syndrome

• Unusual facies

• Webbed neck

• Congenital heart disease

• Short stature

• Chest deformity

What is the most common cardiac defect in Pentalogy of Cantrell, and how common is it?

VSD — 72% of cases.

List the 5 characteristic findings of Pentalogy of Cantrell.

• Abdominal-wall defect

• Lower sternal defect

• Congenital heart malformation

• Absence of diaphragmatic pericardium

• Anterior diaphragmatic defect

List the additional heart defects associated with Pentalogy of Cantrell

• TOF

• ASD

• Cardiac diverticulum

• Pulmonic stenosis

• DORV

• Dextrocardia

• TGA

What is Scimitar syndrome, and what 2 additional findings are listed?

A rare CHD with anomalous venous return from the right lung into systemic venous drainage rather than directly into the LA.

Also associated with:

1. Right PA hypoplasia

2. Right lung hypoplasia

List the 3 cardiac diseases associated with sickle cell anemia.

• Pulmonary hypertension

• LV diastolic heart disease

• Dysrhythmias

What causes sickle cell anemia according to the slide?

Mutated hemoglobin S (HbS) produces rigid, sticky RBCs shaped like sickles that may block small vessels and reduce blood flow/oxygen delivery.

List the cardiac effects of scleroderma given in the slide.

• Abnormal heart rhythms

• CHF

• Inflammation of the sac surrounding the heart

• Increased right-sided heart pressure

List the 4 left-sided defects associated with Shone syndrome.

• Supravalvular mitral membrane

• Parachute mitral valve

• Subaortic stenosis

• Coarctation of the aorta

What symptoms may children with Shone syndrome develop?

• Fatigue

• Nocturnal cough

• Reduced cardiac output by about age 2

• Wheezing from fluid in the lungs

List the 4 heart conditions associated with SLE.

• Leaflet abnormalities

• Pericarditis

• Myocarditis

• Libman-Sacks endocarditis

List the 4 cardiac defects associated with Down syndrome.

• AV septal defect

• VSD

• ASD

• TOF

What chromosomal abnormality causes Down syndrome?

An extra copy of chromosome 21 — Trisomy 21.

How often do patients with Trisomy 18 have cardiac defects, and list the 5 defects given.

99% have cardiac defects.

1. Bicuspid aortic valve

2. Pulmonary stenosis

3. VSD

4. ASD/AV septal defect

5. DORV

What is the survival statement given for Trisomy 18?

About half of affected infants do not survive beyond the first week of life.

What is the chance of a cardiac defect in Trisomy 13, and list the defects given.

90% or greater.

1. VSD

2. ASD

3. Dextroposition

4. HLHS

What does the slide state about the severity and survival of Patau syndrome?

• Least common and most severe viable autosomal trisomy

• Median survival is fewer than 3 days

What cardiac tumor is associated with tuberous sclerosis, and how common is it?

Rhabdomyomas — 50–60%.

They are usually largest at birth and shrink as the child gets older.

List the 3 cardiac defects associated with Turner syndrome.

• Coarctation of the aorta

• Bicuspid aortic valve

• ASD

What chromosomal abnormality occurs in Turner syndrome?

One X chromosome is missing, partially missing, or altered.

What is another name for Williams syndrome, and what 2 cardiovascular abnormalities are associated with it?

• Williams-Beuren syndrome

• Supravalvular stenosis

• Peripheral branch PA stenosis

What does CATCH stand for in DiGeorge syndrome?

• Cardiac abnormality

• Abnormal facies

• Thymic aplasia

• Cleft palate

• Hypocalcemia/hypoparathyroidism

List the 4 common cardiac abnormalities associated with DiGeorge syndrome.

• Truncus arteriosus

• Interrupted aortic arch

• Coarctation of the aorta

• TOF

What chromosomal abnormality causes DiGeorge syndrome?

22q11.2 deletion — a small portion of chromosome 22 is missing.

List the 3 cardiac abnormalities associated with muscular dystrophy.

• Dilated cardiomyopathy

• Conduction abnormalities — RBBB and AV block

• Inferoseptal aneurysms

What 2 types of muscular dystrophy are listed, and how do they differ?

• Duchenne: Worsens quickly

• Becker: Progresses more slowly

The slide also states it is more prevalent in males and begins in the legs and pelvis.

What is Marfan syndrome, and list the 4 body systems it commonly affects.

An inherited connective-tissue disorder affecting:

1. Heart

2. Eyes

3. Blood vessels

4. Skeleton Session

What 2 cardiac defects are listed for Ehlers-Danlos syndrome?

• Mitral valve prolapse

• Dilated aorta

List the 4 cardiovascular abnormalities associated with Loeys-Dietz syndrome.

1. Aortic aneurysms

2. Aortic dissections

3. PDA/ASD

4. Bicuspid aortic valve

Arterial tortuosity may also occur.

What builds up in Fabry disease, and how is it inherited?

• Sphingolipids build up in blood-vessel walls and organs

• Inherited in an X-linked manner

List the 3 cardiac manifestations of Fabry disease.

• HCM with concentric thickening, no LVOT obstruction, and diastolic dysfunction

• Arrhythmias such as complete heart block

• Thickened left-sided valves

What builds up in Pompe disease, and where does it especially cause damage?

Glycogen builds up in cells, especially in muscles, causing tissue breakdown.

What major cardiac disease is associated with Pompe disease?

Pompe disease is listed as a leading cause of familial/idiopathic hypertrophic cardiomyopathy

What 2 cardiac defects are associated with Ellis-Van Creveld syndrome?

• ASD

• Common atrium**

What major physical condition is associated with Ellis-Van Creveld syndrome?

An inherited bone-growth disorder causing very short stature/dwarfism.

What causes Hunter syndrome?

A missing or malfunctioning iduronate 2-sulfatase enzyme, causing complex molecules to build up in harmful amounts.

List the 2 cardiac abnormalities associated with Hunter syndrome.

• Complete heart block

• Left-sided valve disease — mitral stenosis is common

What builds up in Hurler syndrome?

Glycosaminoglycans (GAGs) build up in lysosomes because they cannot be properly broken down.

List the 4 cardiac abnormalities associated with Hurler syndrome.

• Left-sided valve disease

• LVH progressing to systolic and diastolic dysfunction

• Coronary artery disease

• Conduction abnormalities