Ivemark Syndrome

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Ivemark Syndrome

Ivemark syndrome consists of viscero-atrial heterotaxia associated with asplenia. It is also known as asplenia syndrome, heterotaxy syndrome, cardiosplenic syndrome, right atrial isomerism (two morphologically right atrial appendage), or bilateral right-sidedness. The incidence of the syndrome is estimated to be 1/10,000–1/40,000 live births.

GENETICS/BASIC DEFECTS

1. Inheritance: autosomal recessive suggested by:

a. Reports of multiple affected siblings, both males and females, born to normal parents

b. Reports of several instances of parental consanguinity c. Report of mutations in the gene encoding connexin

43 (CX43)

2. Other possible cause: maternal diabetes 3. Heterotaxy syndrome

a. A rare congenital disorder occurring in approximately 0.8% of patients with congenital heart disease b. Often associated with complex cyanotic heart disease

and an abnormal cardiac conduction system c. Consisting of the following two groups of disease:

i. Right isomerism (asplenia syndrome)

a) Commonly has a combination of complete atrioventricular canal defect, total anomalous pulmonary venous return, double outlet right ventricle, and pulmonary stenosis

b) Often has paired atrioventricular nodes that may serve as the substrate for a special reen- trant tachycardia (“nodal-to-atrioventricular nodal tachycardia”)

ii. Left isomerism (polysplenia syndrome)

a) Tends to have less complex cardiac anomalies and therefore a better prognosis b) Likely to have defective sinus and atrioven-

tricular nodes that may result in sinus node dysfunction, junctional escape rhythm, and atrioventricular block

CLINICAL FEATURES

1. Congenital absence of the spleen (asplenia) 2. Congenital heart malformations

a. Cardiac malpositions (44%) i. Dextrocardia

ii. Right sided aortic arch b. Venous system

i. Systemic veins: bilateral superior vena cava (53%) ii. Pulmonary veins

a) Total anomalous pulmonary venous drainage (72%)

b) Partial anomalous pulmonary venous drainage (6%)

c. Great vessels

i. Transposition of the great arteries (72%) ii. Pulmonary stenosis or atresia (78%) d. Coronary arteries: single coronary artery (19%) e. Intracardiac defects

i. Single ventricle (44%) ii. Single AV valve (87%) iii. Absent coronary sinus (85%)

iv. Endocardial cushion defect v. Double inlet ventricle

vi. Discordant ventriculoarterial connection 3. Maldevelopment of the abdominal organs

a. Abnormalities of the mesenteric attachment (intestinal malrotation), a major predisposing cause of mid-gut volvulus

b. Situs inversus (heterotaxia) c. A midline (central) liver d. Tubular stomach e. Imperforate anus

f. Annular pancreas and obstructing duodenal bands g. Esophageal varices

h. Duplication of stomach i. Agenesis of gallbladder j. Rudimentary pancreas k. Meckel diverticulum

l. Esophageal atresia and TE fistula m. Hiatus hernia

n. Gastric hypoplasia

o. Acute gastric volvulus: a rare complication p. Cleft palate

q. Duplication of the hindgut r. Aganglionosis

4. Bronchopulmonary isomerism a. Abnormal lobation of the lungs

i. Bilaterally tri-lobed ii. Bilateral bi-lobed b. Bilateral eparterial bronchi c. Pulmonary hypoplasia 5. CNS malformations: uncommon

a. Agenesis of the corpus callosum b. Porencephalic cyst

c. Cerebellar cysts

d. Focal cerebellar dysplasia e. Hydrocephalus

f. Septum pellucidum abnormality 6. Genitourinary anomalies

a. Horseshoe kidney b. Cystic kidney

c. Bilobed urinary bladder d. Hydroureter

e. Posterior urethral valves

f. Ureteral valve with hydronephrosis g. Double collecting system

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h. Recto-urethral fistula i. Bicornuate uterus j. Ovarian cysts 7. Endocrine abnormalities

a. Fused or horseshoe adrenal b. Absent adrenal

8. Musculoskeletal abnormalities a. Equinovarus deformity b. Overlapping toes c. Clubbing of hands d. Absent radii 9. Miscellaneous

a. Microphthalmia b. Single umbilical artery 10. Prognosis

a. Prognosis related to cardiac malformations i. Severe and incompatible with life (as a rule) ii. Anoxia

iii. Cyanotic neonates die from cardiac insufficiency iv. Most die from cardiac disease during the first

year of life (usually the 1st month) v. Complications of surgery

vi. Hemorrhage

b. Prognosis related to asplenia

i. Greater risk from infection for those who survive the first 12 months

ii. Sudden death in infancy from sepsis and impaired resistance to infection

DIAGNOSTIC INVESTIGATIONS

1. Echocardiography for delineating congenital heart defects 2. Diagnosis of asplenia

a. No splenic uptake on technetium sulfur colloid scan b. Presence of Howell-Jolly bodies in a peripheral blood

smear after the first week of life

3. Immunologic assessment in congenital asplenia a. Quantitation of serum immunoglobulins b. Most common pathogens

i. In children less than 6 months of age a) Escherichia coli

b) Klebsiella

ii. In children surviving past 6 months of age a) Haemophillus influenzae

b) Pneumococci

GENETIC COUNSELING

1. Recurrence risk a. Patient’s sib: 25%

b. Patient’s offspring: not increased unless the spouse is a carrier or affected

2. Prenatal diagnosis by fetal echocardiography

a. No identifiable spleen (The fetal spleen can usually be detected at 20 weeks of gestation in the left gas- trorenal angle.)

b. Levocardia

c. Complete atrioventricular septal defect d. Double outlet right ventricle

e. Dextro malposition of the great arteries

f. Pulmonary atresia/stenosis g. Other cardiac anomalies 3. Management

a. Prophylactic antibiotics to prevent life-threatening sepsis

b. Palliative cardiac surgery for congenital heart defects c. Surgical intervention for gastrointestinal malforma-

tions and other anomalies

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Fig. 1. A 3-month-old with Ivemark syndrome who has asplenia with complex cardiovascular malformations (AV canal, single ventricle, transposition of the great vessels, pulmonary atresia, and total anomalous pulmonary venous return). She also has malrotation of intestine.

Fig. 2. A 19-month-old boy with Ivemark syndrome. He had heterotaxy syndrome with asplenia, situs ambiguous, and complex congenital heart defects consisting of a single ventricle, atrioventricular septal defect with small ostium primum ASD, pulmonary stenosis, interrupted IVC with azygous continuation to a left SVC, right aortic arch, and congenital complete heart block.