Chediak-Higashi Syndrome Clinical Presentation

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

History

Infants born with Chédiak-Higashi syndrome have nonpigmented skin (similar to albinos but in patchy distribution), blonde hair, and blue eyes.

Signs and symptoms that usually appear soon after birth include the following:

  • Adenopathy
  • Aphthae
  • Gingivitis
  • Hyperhidrosis
  • Miliaria
  • Jaundice
  • Severe and extensive pyoderma
  • Recurrent sinopulmonary infections
  • Fever unrelated to recognizable infection
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Physical

Oculocutaneous albinism is prominent, and, together with photophobia and silvery hair, it is helpful in early diagnosis. The skin is fair, the retinae are pale, and the irides are translucent. The hair is light blonde or silvery gray and may be sparse.

In Chédiak-Higashi syndrome, patients are affected by frequent and severe pyogenic infections secondary to abnormal functioning of polymorphonuclear leukocytes, which is associated with albinism and a bleeding tendency.

Recurrent skin infections occur frequently and range from superficial pyoderma to deep subcutaneous abscesses and ulcers that heal slowly and result in atrophic scars. S aureus is the most common causative agent. Deep ulcerations resembling pyoderma gangrenosum have also been described.

The complete syndrome includes oculocutaneous albinism with photophobia, neurologic features, recurrent infections, and enterocolitis.

Lymphadenopathy and hepatosplenomegaly are variable.

Severe gingivitis and oral mucosal ulceration are common. Oral ulcerations and periodontal disease also occur.[8, 9]

Chédiak-Higashi syndrome may present with neurologic dysfunction and should be considered in the differential diagnosis of children and young adults first seen with symptoms of spinocerebellar degeneration or movement disorders. Common physical findings include abnormal gait, clumsiness, seizures, paresthesia, mental retardation, and peripheral neuropathy. In many persons with Chédiak-Higashi syndrome, neurologic changes appear in the lymphoproliferative lymphomalike phase. Progressive neurologic deterioration is common in patients who survive early childhood. Generally, such patients eventually enter an accelerated phase of the disease with widespread infiltration by lymphocytes and histiocytes, causing rapid enlargement of the liver, the spleen, and the lymph nodes, and with concurrent severe leukopenia and thrombocytopenia, resulting in death from infection or bleeding.

The adult form of Chédiak-Higashi syndrome manifests during late childhood to early adulthood and is marked by various neurologic sequelae, including parkinsonism, dementia, spinocerebellar degeneration, and peripheral neuropathy.

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Causes

The underlying defect in Chédiak-Higashi syndrome remains elusive, but the disorder can be considered a model for defects in vesicle formation, fusion, or trafficking.

Chédiak-Higashi syndrome is inherited in an autosomal recessive pattern. Parental consanguinity is often reported. The Chédiak-Higashi syndrome locus on human chromosome 1 encodes a lysosomal trafficking regulator, formerly termed LYST (currently termed CHS1), which is defective in patients with CHS.[10, 11] Patients with Chédiak-Higashi syndrome exhibit alterations in neutrophils. These alterations include neutropenia, which may be profound; decreased deformability, resulting in impaired chemotaxis; and delayed phagolysosomal fusion, resulting in impaired bactericidal activity.

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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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