Introduction

CHEDIAK HIGASHI SYNDROME is a rare, autosomal genetic-recessive disorder with a very high mortality rate and that is characterized recurrent bacterial infections, easy bruising, oculocutaneous albinism among other signs and symptoms.

This condition was first described by an individual called Beguez-Cesar.

Then, discoveries were made about the maldistribution of myeloperoxidases in granules of neutrophils of the affected persons by Chediak and Higashi in 1952 and 1954 respectively.

 

 Key Data & Insights

What are the facts and statistics that surround CHS?

• It is a rare disorder.
• Estimated incidence stands at less than 1 per 1,000,000 persons.
• The exact prevalence is not yet established.
• Globally, less than 500 cases have so far been reported.
• It has a very high mortality rate. About 90% of patients die within the first 10 years of their lives.

 

 Understanding Causes

What causes CHS?

• CHS is caused by a mutation in the lysosomal trafficking regulator (LYST) gene, otherwise known as Chediak-Higashi syndrome (CHS1) gene.
• LYST gene is found on the long arm (q) of chromosome number 1.
• Several mutations have been discovered so far and they include:

1.  Missense mutations.
2.  Nonsense mutations.
3.  Deletions.
4.  Insertions.

 

CHS1 gene:

• Controls lysosomal trafficking.
• Manufacture, fusion and transport of cytoplasmic granules.

 

• Mutation in the lysosomal regulator trafficking protein causes:

1.  Reduction in phagocytosis.
2. Predisposition to recurrent bacterial illness.

• CHS can also be caused by inheritance of the defective gene. Being an autosomal recessive condition, each parent (being a carrier of a non-functional copy of a gene) must pass the gene to the offspring for the disease to develop and symptoms to show.

 

Associated Risk Factors

What are the risk elements for CHS development?

• Being born to parents who are carriers of LSYT defective gene.
• Mutation in the CHS1 gene.

 

 Symptoms & Symptoms

Manifestations and indicators of CHS

• Children with CHS may present with:

1. Silvery hair and light-colored eyes ( oculocutaneous albinism).
2. Frequent infections of the skin and mucosal membranes.
3. Nystagmus (rapid, involuntary eye movements).
4. Decreased vision.
5. Siezures.
6. Photophobia.
7. Peripheral neuropathy.
8. Easy bruising.
9. Muscle weakness.
10. Intellectual disability.
11. Ataxia.
12. Coagulation disorders.
13. Abnormal functions of the natural killer cells.
14. Immunodeficiency and recurrent pyogenic infections.

 

 Diagnostic Methods

How is CHS diagnosed?

• Patient history-taking. This involves review of presenting symptoms among other relevant histories.
• Clinical examination.
• Tests. Several types of tests can be conducted and this are:

1.  Electroencephalography (EEG).
2.  Magnetic resonance imaging of the brain.
3.  Brain computed tomography scan.
4.  Nerve conduction tests.
5. Complete blood count (CBC).
6. Platelet counts.

 

Management & Treatment Options

How is CHS managed?

• There lacks a specific treatment for CHS.
• Currently, treatment strategies are aimed dealing with clinical symptoms:

1. Hematological and immune deficiency. The only cure is allogeneic hematopoietic stem cell transplantation.
2. Hypopigmentation. Wear sunscreen to prevent cancer of the skin.
3. Neurological symptoms. For older patients, early rehabilitation should be embraced as the symptoms of CHS are progressive.
4. Ocular symptoms. Wear sunglasses as this protects against harmful UV rays. Correction of refractive errors might lead to improvement in visual acuity.

 

• The following strategies can be employed to prevent secondary manifestations:

1. Immunizations.
2. Before performing invasive procedures, administer desmopressin intravenously  for half hour to aid in controlling bleeding.
3. Avoid giving non-steroidal anti-inflammatory drugs. They can exacerbate bleeding tendencies.
4. Bacterial infections are treated with anti-biotic agents.
5. Avoid exposure to infectious microbes.

 Complications  & Consequences

What are the complications and consequences of CHS?

• There are several complications and consequences associated with CHS.
• These include:

1. Frequent infections such as bacterial illnesses.
2. Lymphoma.
3. Premature death. Death mostly happens within the first 10 years of life due to:
4.  Chronic infections.
5.  Diseases that lead to development of lymphoma-like disease (hemophagocytic lymphohistiocytosis).
6. Neurological symptoms. A few individuals who make it to adulthood develop neurological symptoms.

 

Differential Diagnosis

• This includes other genetic conditions that present with oculocutaneous albinism.

1.  Hermansky-Pudiak synrome.
2.  Griscelli syndrome.

 

• Other considerations include:

1.  Familial hemophagocytic lympkohistiocytosis.
2.  Cross syndrome.

 

 Strategies for Prevention

How can CHS be prevented?

Genetic counselling and testing for individuals from families with a history of Chediak-Higashi syndrome and who wish to conceive.