Skip to main content

Ondine Syndrome

Ondine Syndrome



Overview

Ondine Syndrome, or Congenital Central Hypoventilation Syndrome (CCHS), is a rare genetic disorder where the autonomic nervous system fails to control breathing automatically, especially during sleep, leading to dangerously low oxygen and high carbon dioxide levels (hypoventilation). Named after a myth about a nymph's curse, it's caused by PHOX2B gene mutations and often involves other issues like Hirschsprung's disease (Haddad Syndrome) or neural crest tumors, requiring lifelong mechanical ventilation, often via diaphragm pacing. 

Symptoms

Respiratory: Inadequate or absent breathing (apnea/hypoventilation) during sleep (most common), with normal breathing while awake; can be severe enough to affect waking hours.

Neurological/Autonomic:

Abnormal pupil responses (pupillary anomalies, strabismus).

Poor heart rate variability, arrhythmias, or bradycardia (slow heart rate).

Difficulty swallowing (dysphagia) or esophageal dysmotility.

Altered temperature regulation, breath-holding spells, or fainting.

Gastrointestinal: Often linked with Hirschsprung's disease (absent bowel function) or acid reflux.

Other:

Cyanosis (bluish skin) from low oxygen.

Drowsiness, headaches, fatigue.

Sensitivity to sedatives and narcotics, making breathing worse. 

Associated Conditions (Neurocristopathies) 

Hirschsprung's Disease: A significant portion of CCHS patients also have this bowel condition.

Neuroblastoma/Tumors: Tumors of neural crest origin (like neuroblastoma) can occur. 

Causes

Genetic Causes (CCHS)

PHOX2B Gene Mutation: The main culprit, responsible for 90% of cases, impacting the development of neural crest cells that form part of the autonomic system.

Types of Mutations: Can be polyalanine repeat expansion mutations (PARMs) or non-PARMs, influencing severity and associated conditions like Hirschsprung's disease. 

Acquired Causes (Central Hypoventilation Syndrome)

Brainstem Damage: Injury or disease affecting the lower brainstem (medulla) can disrupt respiratory control.

Examples: Stroke, tumors, infections, trauma (like spinal cord injury), or neurodegenerative disorders (Parkinson's, multiple sclerosis). 

Risk Factor 

Genetic Factors (Congenital CCHS)

PHOX2B Gene Mutation: The primary cause, affecting neural crest cell development, usually a new (de novo) mutation, but can be passed on.

Inheritance Pattern: Autosomal dominant, but often appears as a new mutation, with a potential for parental germline mosaicism (risk of recurrence in future pregnancies). 

Acquired Factors (Late-Onset CCHS)

Brainstem Damage: Damage to the lower brainstem (medulla) is key, from:

Stroke (infarction or hemorrhage)

Brain tumors

Infections (like polio, pneumonia)

Trauma

Triggers: Respiratory infections, general anesthesia, or certain drugs can unmask underlying hypoventilation in susceptible individuals. 

Associated Conditions & Risk Factors (for Syndromic CCHS)

Neurocristopathies: PHOX2B mutations can also cause other conditions, increasing risk and severity:

Hirschsprung disease (intestinal disorder)

Neuroblastoma (nerve tumor)

Autonomic dysfunction (abnormal pupils, heart rate issues). 

Complications

Respiratory & Cardiac Complications:

Chronic Hypoxemia (Low Oxygen): Inadequate breathing during sleep causes oxygen deprivation, stressing the heart and lungs.

Pulmonary Hypertension: High blood pressure in the lungs due to chronic low oxygen.

Cardiac Arrhythmias & Heart Failure: The heart struggles to pump enough oxygenated blood. 

Neurological & Developmental Complications:

Brain Damage: Prolonged lack of oxygen can harm brain development.

Psychomotor & Growth Retardation: Slower development in children.

Autonomic Nervous System Dysfunction: Affects involuntary functions like pupil response, heart rate, and bowel control. 

Associated Conditions (Neurocristopathies):

Hirschsprung's Disease: Absent nerve cells in the colon, causing severe constipation.

Neuroblastoma: A type of nerve cancer.

Neuroganglioma: Tumors of nerve cells. 

Diagnosis

Clinical Suspicion: Symptoms like cyanosis (bluish skin), poor breathing during sleep, or feeding difficulties in newborns raise suspicion.

Sleep Study (Polysomnography): This is crucial to show shallow breathing (hypoventilation) or apnea (no breathing) during sleep, especially in quiet sleep (NREM).

Rule Out Other Conditions:

Neurological/Cardiac: Brain MRI, echocardiogram, and chest X-rays to check for brainstem issues or heart problems.

Gastrointestinal: Rectal biopsy to check for Hirschsprung's disease, a common association.

Metabolic: Blood tests for carnitine levels.

Genetic Testing: Confirming a mutation in the PHOX2B gene is the gold standard for diagnosing CCHS.

Autonomic Testing: Assessing pupillary response and other autonomic functions (like sweating). 

Associated Findings (Neurocristopathies):

Hirschsprung's Disease: Impaired bowel function.

Tumors: Increased risk of neuroblastoma.

Ocular Abnormalities: Abnormal pupils, strabismus (crossed eyes). 

Treatments

Mainstay Treatments (Respiratory Support)

Mechanical Ventilation: The cornerstone of treatment, providing breath support, sometimes 24/7, using ventilators.

Tracheostomy: Often needed for long-term invasive ventilation.

Non-Invasive Ventilation (NIV): Masks or cuirass devices (like biphasic cuirass) can be used, sometimes avoiding tracheotomy.

Diaphragm Pacing: An alternative that stimulates the diaphragm, offering more freedom than traditional ventilators. 

Other Supportive Therapies

Gastrointestinal (GI) Management: Medications and procedures for digestive issues.

Cardiovascular Support: Treatments for blood pressure and heart rate issues.

Ophthalmology Care: Glasses, contacts, or surgery for vision problems.

Growth Hormone Therapy: May be used in some cases.

Monitoring: Regular checks for associated conditions like tumors and sleep disorders. 

Future & Research

Pharmacological: Some medications (like desogestrel) have shown promise in improving chemosensitivity.

Genetic Therapies: Research is exploring gene-targeted therapies (like CRISPR) for a potential cure. 

Type of Doctor Department : A pulmonologist and a neurologist. 


Comments

Post a Comment

Popular posts from this blog

Charge Syndrome

Overview CHARGE syndrome is a recognizable genetic syndrome with known pattern of features. It is an extremely complex syndrome, involving extensive medical and physical difficulties that differ from child to child. CHARGE syndrome is correlated with genetic mutation to CHD7 and the prevalence of CHARGE syndrome is 1:10,000-1:15,000 live births. Babies with CHARGE syndrome are often born with life-threatening birth defects. They spend many months in the hospital and undergo many surgeries and other treatments. Swallowing and breathing problems make life difficult even when they come home. Most have hearing two little girls sitting on a carpet, one girl has a trach and is biting her finger.loss, vision loss, and balance problems that delay their development and communication. Despite these seemingly insurmountable obstacles, children with CHARGE syndrome often far surpass their medical, physical, educational, and social expectations. One of the hidden features of CHARGE syndrome is the ...
7 comments
Read more

HMSN Type I

 HMSN Type I Overview Hereditary motor and sensory neuropathy type 1 (HMSN I), also known as Charcot-Marie-Tooth disease type 1 (CMT1), is a group of inherited neurological disorders affecting the peripheral nerves. It is characterized by progressive muscle weakness and wasting, primarily in the feet and legs, as well as sensory loss. HMSN I is the most common form of HMSN and is typically caused by a duplication on chromosome 17p11.2-p12, including the PMP22 gene.  Symptoms Numbness and tingling: Often starting in the feet and potentially extending to the hands, these sensations can mimic poor circulation.  Reduced ability to feel pain and temperature: This can lead to unnoticed injuries and complications.  Motor Symptoms: Muscle weakness and wasting: Primarily affecting the distal muscles (those farthest from the body's core), such as the feet and hands.  Foot deformities: High arches (pes cavus) and hammer toes are frequently observed.  Gait abnormalit...
Post a Comment
Read more

Sjogren's syndrome

Sjogren's syndrome Overview Sjogren's (SHOW-grins) syndrome is a disorder of your immune system identified by its two most common symptoms — dry eyes and a dry mouth. The condition often accompanies other immune system disorders, such as rheumatoid arthritis and lupus. In Sjogren's syndrome, the mucous membranes and moisture-secreting glands of your eyes and mouth are usually affected first — resulting in decreased tears and saliva. Although you can develop Sjogren's syndrome at any age, most people are older than 40 at the time of diagnosis. The condition is much more common in women. Treatment focuses on relieving symptoms. Symptoms The two main symptoms of Sjogren's syndrome are: Dry eyes . Your eyes might burn, itch or feel gritty — as if there's sand in them. Dry mouth. Your mouth might feel like it's full of cotton, making it difficult to swallow or speak. Some people with Sjogren's syndrome also have one or more of the following: Joint pain, swel...
Post a Comment
Read more