Sudden infant death syndrome pathophysiology

# Overview
The exact pathogenesis of Sudden infant death syndrome (SIDS) is not fully understood. It is thought that Sudden infant death syndrome (SIDS) may be caused by either genetic mutations, brainstem abnormality, airflow obstruction, maternal smoking, or infection.

# Pathophysiology

## Pathogenesis
- The exact pathogenesis of Sudden infant death syndrome (SIDS) is not completely understood.
- The pathogenesis of Sudden infant death syndrome (SIDS) involves the following:
Brain anomalies
- New evidence shows that brainstem anomalies which involves cardiorespiratory control in the midbrain is a significant player in developing Sudden infant death syndrome (SIDS).
- Abnormal 5-hydroxytryptamine  which is also called serotonin signalling pathway  is also implicated in the pathogenesis of developing Sudden infant death syndrome (SIDS).
- Alterations in the serotonin signalling pathway leads to disturbances in medulla which in turn results in disturbances in autonomic processes.
- It is important to note that serotonin signalling pathway is altered by the effect of nicotine, which can relate maternal smoking and the development of sudden infant death syndrome (SIDS).
- New studies have shown that the underdevelopment or abnormal alterations of arcuate nucleus in the Sudden infant death syndrome (SIDS) patients.
Genetics
- The exact involvement of genetic changes is not clear in the pathogenesis of Sudden infant death syndrome (SIDS)
- With the recent research we can say that Sudden infant death syndrome (SIDS) is not a genetic disorder but identification of genetic polymorphisms along with the risk factors increase the risk of developing susceptibility to Sudden infant death syndrome (SIDS)
- Such genetic polymorphisms along with the risk factors in the following genes plays a very crucial role in developing Sudden infant death syndrome (SIDS):
SCN5A gene (Sodium Voltage-Gated Channel Alpha Subunit 5)
SCN5A gene encodes for ion channels on heart
SCN4A gene (Sodium Voltage-Gated Channel Alpha Subunit 4)
SCN4A gene encodes for ion channels on skeletal muscles
KCNQ1 gene (Potassium Voltage-Gated Channel Subfamily Q Member 1)
KCNQ1 gene encodes for functional potassium channels on heart and inner ear.
KCNJ8 gene (Potassium Inwardly Rectifying Channel Subfamily J Member 8)
KCNJ8 gene encodes for Kir6.1 protein and plays an very important role in cardiac repolarization.
KCNH2 gene (Potassium Voltage-Gated Channel Subfamily H Member 2)
KCNH2 gene encodes for voltage-Gated Potassium Channel Subunit Kv11.1
RYR2 (Ryanodine receptor 2)
Ryanodine receptor 2 (RyR2) encodes for Ca2+ release channel.
Serotonin transporter gene
Plays a very crucial role in serotonergic and noradrenergic transmission
Monoamine oxidase A (MAOA) gene
Plays a very crucial role in serotonergic and noradrenergic transmission
Interleukin-10 promoter gene
Interleukin-10 promoter gene encodes for Interleukin-10 anti-inflammatory cytokine
Testis-specific Y-like gene
Testis-specific Y-like gene polymorphism results in loss of sexual differentiation and brainstem-mediated sudden death
Heat shock proteins gene
Polymorphism in heat shock proteins gene results in mutated hsp70 and hsp90.
- SCN5A gene (Sodium Voltage-Gated Channel Alpha Subunit 5)
SCN5A gene encodes for ion channels on heart
- SCN5A gene encodes for ion channels on heart
- SCN4A gene (Sodium Voltage-Gated Channel Alpha Subunit 4)
SCN4A gene encodes for ion channels on skeletal muscles
- SCN4A gene encodes for ion channels on skeletal muscles
- KCNQ1 gene (Potassium Voltage-Gated Channel Subfamily Q Member 1)
KCNQ1 gene encodes for functional potassium channels on heart and inner ear.
- KCNQ1 gene encodes for functional potassium channels on heart and inner ear.
- KCNJ8 gene (Potassium Inwardly Rectifying Channel Subfamily J Member 8)
KCNJ8 gene encodes for Kir6.1 protein and plays an very important role in cardiac repolarization.
- KCNJ8 gene encodes for Kir6.1 protein and plays an very important role in cardiac repolarization.
- KCNH2 gene (Potassium Voltage-Gated Channel Subfamily H Member 2)
KCNH2 gene encodes for voltage-Gated Potassium Channel Subunit Kv11.1
- KCNH2 gene encodes for voltage-Gated Potassium Channel Subunit Kv11.1
- RYR2 (Ryanodine receptor 2)
Ryanodine receptor 2 (RyR2) encodes for Ca2+ release channel.
- Ryanodine receptor 2 (RyR2) encodes for Ca2+ release channel.
- Serotonin transporter gene
Plays a very crucial role in serotonergic and noradrenergic transmission
- Plays a very crucial role in serotonergic and noradrenergic transmission
- Monoamine oxidase A (MAOA) gene
Plays a very crucial role in serotonergic and noradrenergic transmission
- Plays a very crucial role in serotonergic and noradrenergic transmission
- Interleukin-10 promoter gene
Interleukin-10 promoter gene encodes for Interleukin-10 anti-inflammatory cytokine
- Interleukin-10 promoter gene encodes for Interleukin-10 anti-inflammatory cytokine
- Testis-specific Y-like gene
Testis-specific Y-like gene polymorphism results in loss of sexual differentiation and brainstem-mediated sudden death
- Testis-specific Y-like gene polymorphism results in loss of sexual differentiation and brainstem-mediated sudden death
- Heat shock proteins gene
Polymorphism in heat shock proteins gene results in mutated hsp70 and hsp90.
- Polymorphism in heat shock proteins gene results in mutated hsp70 and hsp90.

## Cardiac dysfunction
- According to some new studies the following cardiac alterations are found in SIDSpatients :
Increase in heart rate (sinus tachycardia) which results in SIDS
Long QT intervals on ECG
- Increase in heart rate (sinus tachycardia) which results in SIDS
- Long QT intervals on ECG

## Triggers
Prone position
- The exact pathogenesis of prone position and the development of sudden infant death syndrome (SIDS) is not completely understood.
- According to some new studies infant being in prone position increases the risk of infant to the following:
Suffocation of the baby
Decrease in arousal of the baby
Overheating of the baby
- Suffocation of the baby
- Decrease in arousal of the baby
- Overheating of the baby

# Gross Pathology
- On gross pathology, the following features are characteristic findings of SIDS.
Intrathoracic petechial hemorrhages
Numerous petechiae within the thymus and epicardium and plural visceral surfaces is a very distinctive feature of SIDS.
Positive beckwiths sign which is uneven distribution of petechiae on the dorsal portions of the cervical lobes of the thymus
Edematous and congested lungs on gross examination.
Left ventricular hypertrabeculation
- Intrathoracic petechial hemorrhages
Numerous petechiae within the thymus and epicardium and plural visceral surfaces is a very distinctive feature of SIDS.
- Numerous petechiae within the thymus and epicardium and plural visceral surfaces is a very distinctive feature of SIDS.
- Positive beckwiths sign which is uneven distribution of petechiae on the dorsal portions of the cervical lobes of the thymus
- Edematous and congested lungs on gross examination.
- Left ventricular hypertrabeculation

# Microscopic Pathology
- On microscopic histopathological analysis, the following features are characteristic findings of SIDS:
Submucosal chronic inflammatory cells in the lung tissues
Intra-alveolar hemorrhage
Hemosiderin within intra-alveolar macrophages
Thick, pseudostratified ependymal layer in brain stem can be seen by using Kluver-Barrera stain.
- Submucosal chronic inflammatory cells in the lung tissues
- Intra-alveolar hemorrhage
- Hemosiderin within intra-alveolar macrophages
- Thick, pseudostratified ependymal layer in brain stem can be seen by using Kluver-Barrera stain.
- Focal granule cell dispersion in the dentate gyrus can be seen on microscopy of the brain in SIDS.
- Hippocampus of an infant shows with sudden unexplained death with focal granule cell bilamination in SIDS.
- Clusters of immature cells can be seen in the dentate gyrus of brain on microscopy.