Chediak-Higashi Syndrome 

  • Author: Roman Janusz Nowicki, MD, PhD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jul 13, 2011
 

Background

Chédiak-Higashi syndrome (CHS) is a rare childhood autosomal recessive disorder that affects multiple systems of the body. Patients with CHS exhibit hypopigmentation of the skin, eyes, and hair; prolonged bleeding times; easy bruisability; recurrent infections; abnormal natural killer cell function; and peripheral neuropathy. Morbidity results from patients succumbing to frequent bacterial infections or to an accelerated-phase lymphoproliferation into the major organs of the body. Most patients who do not undergo bone marrow transplantation die of a lymphoproliferative syndrome, although some patients with CHS have a relatively milder clinical course of the disease. CHS was described by Beguez Cesar in 1943, Steinbrinck in 1948, Chédiak in 1952, and Higashi in 1954.[1, 2, 3] .

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Pathophysiology

Chédiak-Higashi syndrome is an autosomal recessive immunodeficiency disorder characterized by abnormal intracellular protein transport. The Chédiak-Higashi syndrome gene was characterized in 1996 as the LYST or CHS1 gene and is localized to bands 1q42-43. The CHS protein is expressed in the cytoplasm of cells of a variety of tissues and may represent an abnormality of organellar protein trafficking.[4, 5]

The Chédiak-Higashi syndrome gene affects the synthesis and/or maintenance of storage/secretory granules in various types of cells. Lysosomes of leukocytes and fibroblasts, dense bodies of platelets, azurophilic granules of neutrophils, and melanosomes of melanocytes are generally larger in size and irregular in morphology, indicating that a common pathway in the synthesis of organelles responsible for storage is affected in patients with Chédiak-Higashi syndrome. In the early stages of neutrophil maturation, normal azurophil granules fuse to form megagranules, whereas, in the later stage (ie, during myelocyte stage), normal granules are formed. The mature neutrophils contain both populations. A similar phenomenon occurs in monocytes. The impaired function in the polymorphonuclear leukocytes may be related to abnormal microtubular assembly.

The disease is often fatal in childhood as a result of infection or an accelerated lymphomalike phase; therefore, few patients live to adulthood. In these patients, a progressive neurologic dysfunction may be the dominant feature. Neurologic involvement is variable but often includes peripheral neuropathy. The mechanism of peripheral neuropathy in Chédiak-Higashi syndrome has not been completely elucidated. Both the axonal type and the demyelinating type of peripheral neuropathy associated with Chédiak-Higashi syndrome have been reported.

Defective melanization of melanosomes occurs in oculocutaneous albinism associated with Chédiak-Higashi syndrome. In melanocytes, autophagocytosis of melanosomes occurs.

Most patients also undergo an accelerated phase or accelerated reaction, which is a nonmalignant lymphohistiocytic lymphomalike infiltration of multiple organs that occurs in more than 80% of patients. This lymphomalike stage is precipitated by viruses, particularly by infection by the Epstein-Barr virus. It is associated with anemia, bleeding episodes, and overwhelming infections leading to death. Infections most commonly involve the skin, the lungs, and the respiratory tract and are usually due to Staphylococcus aureus, Streptococcus pyogenes, and Pneumococcus species.

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Epidemiology

Frequency

United States

Chédiak-Higashi syndrome is rare.

International

Chédiak-Higashi syndrome is rare.[6]

Mortality/Morbidity

Death often occurs in the first decade as a result of infection, bleeding, or development of the accelerated lymphomalike phase, but survival into the second and third decades has been reported.

Race

Chédiak-Higashi syndrome affects all races. Al-Khenaizan suggests that Chédiak-Higashi syndrome may be underreported in persons of darker-skinned races.[7]

Age

Symptoms of Chédiak-Higashi syndrome usually appear soon after birth or in children younger than 5 years.

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Contributor Information and Disclosures
Author

Roman Janusz Nowicki, MD, PhD  Professor, Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, Poland

Roman Janusz Nowicki, MD, PhD is a member of the following medical societies: American Academy of Dermatology, European Academy of Dermatology and Venereology, and International Society for Human and Animal Mycology

Disclosure: Nothing to disclose.

Specialty Editor Board

Jacek C Szepietowski, MD, PhD  Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland

Disclosure: Stiefel GSK Company Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting; Abbott Consulting fee Consulting; Leo Pharma Consulting fee Consulting

Michael J Wells, MD  Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

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