Genetic disorder

1. HETEROTAXY
SYNDROME
DR ALAMIN USMAN MUHAMMAD
PEADIATRIC DEPARTMENT, DASH.

2. OUTLINE
• Introduction
• Overview
• Pathophysiology
• Epidemeology
• Clinical presentation
• Work-up
• Treatment and management
• Prognosis and conclusion
• References

3. INTRODUCTION
• Derived from the Greek word;
• Heteros= different
• Taxis=arrangement
• Syndrome= a condition characterized by a set of associated signs and symptoms
• Thus, it literally means, a pattern of anatomical organization of the thoracic and
abdominal organs which is not the expected usual or normal arrangement.
• Other arrangements are; situs solitus and situs inversus.

5. OVERVIEW
• Heterotaxy syndrome is a rare birth defect , where the internal thoraco-
abdominal organs demonstrate abnormal arrangement across the left-right axis
of the body.
• This involves malformations that leads to congenital heart diseases, abnormal
spleen, absence of some organs such as liver, gall bladder, arrhythmias, and gut
malrotation.
• Different names often used interchangeably for heterotaxy syndrome are; situs
ambiguous and isomerism. Others not commonly used are; ivemark syndrome,
plysplenia-asplenia syndrome and cardio-splenic syndrome.
• There are two variants of heterotaxy sundrome; RAI nad LAI.

6. PATHOPHYSIOLOGY
• Although still poorly understood, the cause of situs ambiguous has been linked
to family history of malformations and maternal drug abuse, suggesting both
genetic and environmental factors play a role.
• Several genes of the TGF-beta pathway, which controls the left-right patterning of
visceral organs across the body axis have been indicated in cases of atrial
isomerism.
• Mutations in the genes that encode proteins in TGF-beta pathway have been
linked with this syndrome.

7. EPIDEMEOLOGY
• Worldwide incidence of heterotaxy syndrome is repotedly 1 case per 10,000
births.
• It accounts for approximately 3% of all congenital heart defects.
• No predilection based on race has been identified
• Two studies however noted a male to female ratio 2:1.
• There is however failure to diagnose and underestimation of the disease by
clinicians, which further reduce the incidence and prevalence of the disease.

8. CLINICAL PRESENTATION
• Right atrial isomerism: dominance of the thoraco-abdominal organs on the right side of the midline,
hence;
• 1- displacement of left atrium with right atrium
• 2-pulmonary veins not draining into LA, therefore drainage into pulmonary artery is seen
(anomalous pulmonary venous drainage) leading to cyanosis.
• Both atria becomes pyramidal in shape
• Extra SVC or IVC
• ASD,AVSD (balanced type)
• 3- Asplenia (infections)
• Gut malrotation (volvulus)

10. • Left atrial isomerism: dominance of the thoraco-abdominal organs on left side of the midline,
hence;
• 1-displacement of right atrium with left atrium
• 2-absent RA leads to interrupted IVC flow, therefore dilatation of azygos and hemiazygos vein
seen as double barrel sign behind heart on echo.
• 3-absent SA node, therefore causes complete heart block
• 4- absent gall bladder or biliary atresia (pale stools, dark urine, malabsorption of nutrients)
• 5- midline liver
• 6- polyslpenia
• 7-unbalanced type AVSD

12. WORK-UP
• NON SPECIFIC ;
• 1-CBC
• 2-PERIPHERAL BLOOD SMEAR (detect Howell jolly bodies)
• SPECIFIC;
• 1-ECHO
• 2-ECG
• CXR
• MRI
• OTHERS
• Genetic testing

13. TREATMENT AND MANAGEMENT
• PALLIATIVE MANAGEMENT;
• 1- PROPHYLACTIC ANTIBIOTICS
• 2-VACCINATION
• 3- DIURETIC AGENTS
• 4-ACE-I
• SURGERY IS THE MAINSTAY OF TREATMENT TO CORRECT THE DEFECTS IN
HETEROTAXY SYNDROME.

14. PROGNOSIS AND CONCLUSION
• The prognosis for heterotaxy syndrome is quite varied, considering the spectrum
of clinical complications.
• 10% of patients born with RAI die by the age of 5 without intervention.
• Improvements in therapies has however increased the 5-year survival to 30-74%
for RAI and 65-84% for LAI.
• In conclusion, those with LAI do better than those with RAI.

15. REFERENCES
• 1- heterotaxy syndrome and primary ciliary dyskinesia, Medscape.
• 2-heterotaxy syndrome, united state National library of medicine.