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Chédiak-Higashi syndrome(CHS)

MedGen UID:
3347
Concept ID:
C0007965
Disease or Syndrome
Synonyms: Chediak-Higashi Syndrome; CHS
SNOMED CT: Chediak-Steinbrinck-Higashi syndrome (111396008); Chediak-Higashi syndrome (111396008); Hereditary gigantism of cytoplasmic organelles (111396008); Granulation anomaly of leukocytes (111396008); Congenital gigantism of peroxidase granules (111396008); Beguez Cesar disease (111396008); Chediak anomaly (111396008); Chediak-Steinbrinck anomaly (111396008); Chédiak-Higashi syndrome (111396008); Chédiak anomaly (111396008); Chédiak-Steinbrinck anomaly (111396008); Hereditary leukomelanopathy (111396008); Steinbrinck anomaly (111396008); Béguez César disease (111396008); Chediak Higashi syndrome (111396008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): LYST (1q42.3)
 
Monarch Initiative: MONDO:0008963
OMIM®: 214500
Orphanet: ORPHA167

Disease characteristics

Excerpted from the GeneReview: Chediak-Higashi Syndrome
Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism (OCA), immunodeficiency, a mild bleeding tendency, and late adolescent- to adult-onset neurologic manifestations (e.g., learning difficulties, peripheral neuropathy, ataxia, and parkinsonism). While present in nearly all individuals with CHS, these clinical findings vary in severity. Of note, all individuals with CHS are at risk of developing neurologic manifestations and hemophagocytic lymphohistiocytosis (HLH). Individuals with severe childhood-onset presentations are considered to have "classic" CHS, whereas individuals with milder adolescent- to adult-onset presentations are considered to have "atypical" CHS. Because of the considerable overlap between classic CHS and atypical CHS, the disorder is best understood as a continuum of severe to milder phenotypes, with the universal feature being the pathognomonic giant granules within leukocytes observed on peripheral blood smear. [from GeneReviews]
Authors:
Camilo Toro  |  Marie Morimoto  |  May Christine Malicdan, et. al.   view full author information

Additional descriptions

From OMIM
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized by hypopigmentation or oculocutaneous albinism with low vision, nystagmus, and photophobia, and severe immunologic deficiency with neutropenia and lack of natural killer cell function. A hallmark of the disorder is giant inclusion bodies in virtually all granulated cells (summary by Fukai et al., 1996). The majority of CHS patients eventually develop a lymphoproliferative syndrome, the 'accelerated phase' of the disorder, characterized by generalized lymphohistiocytic infiltrates, fever, jaundice, hepatosplenomegaly, lymphadenopathy, pancytopenia, and bleeding (summary by Spritz, 1999).  http://www.omim.org/entry/214500
From MedlinePlus Genetics
Chediak-Higashi syndrome is a condition that affects many parts of the body, particularly the immune system. This disease damages immune system cells, leaving them less able to fight off invaders such as viruses and bacteria. As a result, most people with Chediak-Higashi syndrome have repeated and persistent infections starting in infancy or early childhood. These infections tend to be very serious or life-threatening.

Chediak-Higashi syndrome is also characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and light-colored hair, often with a metallic sheen. Oculocutaneous albinism also causes vision problems such as reduced sharpness; rapid, involuntary eye movements (nystagmus); and increased sensitivity to light (photophobia).

Many people with Chediak-Higashi syndrome have problems with blood clotting (coagulation) that lead to easy bruising and abnormal bleeding. In adulthood, Chediak-Higashi syndrome can also affect the nervous system, causing weakness, clumsiness, difficulty with walking, and seizures.

If the disease is not successfully treated, most children with Chediak-Higashi syndrome reach a stage of the disorder known as the accelerated phase. This severe phase of the disease is thought to be triggered by a viral infection. In the accelerated phase, white blood cells (which normally help fight infection) divide uncontrollably and invade many of the body's organs. The accelerated phase is associated with fever, episodes of abnormal bleeding, overwhelming infections, and organ failure. These medical problems are usually life-threatening in childhood.

A small percentage of people with Chediak-Higashi syndrome have a milder form of the condition that appears later in life. People with the adult form of the disorder have less noticeable changes in pigmentation and are less likely to have recurrent, severe infections. They do, however, have a significant risk of progressive neurological problems such as tremors, difficulty with movement and balance (ataxia), reduced sensation and weakness in the arms and legs (peripheral neuropathy), and a decline in intellectual functioning.  https://medlineplus.gov/genetics/condition/chediak-higashi-syndrome

Clinical features

From HPO
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Jaundice
MedGen UID:
43987
Concept ID:
C0022346
Sign or Symptom
Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Progressive loss of neural cells and tissue.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Photophobia
MedGen UID:
43220
Concept ID:
C0085636
Sign or Symptom
Excessive sensitivity to light with the sensation of discomfort or pain in the eyes due to exposure to bright light.
Cranial nerve paralysis
MedGen UID:
57717
Concept ID:
C0151311
Disease or Syndrome
Injury to any of the cranial nerves or their nuclei in the brain resulting in muscle weakness.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Progressive peripheral neuropathy
MedGen UID:
347816
Concept ID:
C1859178
Finding
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Spontaneous, recurrent epistaxis
MedGen UID:
816045
Concept ID:
C3809715
Finding
Abnormal dense granules
MedGen UID:
868491
Concept ID:
C4022885
Anatomical Abnormality
Defective structure, size or content of dense granules, platelet organelles that contain granules proaggregatory factors such as adenosine diphosphate (ADP), adenosine triphosphate (ATP), ionized calcium, histamine and serotonin.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Periodontitis
MedGen UID:
45815
Concept ID:
C0031099
Disease or Syndrome
Inflammation of the periodontium.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Lymphadenopathy
MedGen UID:
96929
Concept ID:
C0497156
Disease or Syndrome
Enlargment (swelling) of a lymph node.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Hemophagocytosis
MedGen UID:
163750
Concept ID:
C0876991
Disease or Syndrome
Phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.
Recurrent bacterial skin infections
MedGen UID:
322727
Concept ID:
C1835686
Finding
Increased susceptibility to bacterial infections of the skin, as manifested by recurrent episodes of infectious dermatitis.
Impaired neutrophil bactericidal activity
MedGen UID:
868687
Concept ID:
C4023090
Finding
A reduction in the ability of neutrophils to kill bacteria.
Recurrent systemic pyogenic infections
MedGen UID:
870741
Concept ID:
C4025196
Disease or Syndrome
Increased susceptibility to systemic pyogenic infections, as manifested by recurrent episodes of systemic pyogenic infections.
Giant neutrophil granules
MedGen UID:
1693344
Concept ID:
C5139386
Finding
The presence of abnormally large granules in neutrophils. This finding can be appreciated on a peripheral blood smear. The finding is characteristic of Chediak Higashi syndrome. The giant granules are derived from azurophil granules, whereas peroxidase-negative granules are not involved in their formation.
Gingivitis
MedGen UID:
4895
Concept ID:
C0017574
Disease or Syndrome
Inflammation of the gingiva.
Hypopigmentation of the skin
MedGen UID:
102477
Concept ID:
C0162835
Disease or Syndrome
A reduction of skin color related to a decrease in melanin production and deposition.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Silver-gray hair
MedGen UID:
322949
Concept ID:
C1836576
Finding
Hypopigmented hair that appears silver-gray.
Hypopigmentation of hair
MedGen UID:
480031
Concept ID:
C3278401
Finding
Giant melanosomes in melanocytes
MedGen UID:
812551
Concept ID:
C3806221
Finding
The presence of large spherical melanosomes (1 to 6 micrometer in diameter) in the cytoplasm of melanocytes.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Ocular albinism
MedGen UID:
38147
Concept ID:
C0078917
Congenital Abnormality
An abnormal reduction in the amount of pigmentation (reduced or absent) of the iris and retina.
Iris hypopigmentation
MedGen UID:
509721
Concept ID:
C0154920
Finding
An abnormal reduction in the amount of pigmentation of the iris.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Macular hypoplasia
MedGen UID:
340322
Concept ID:
C1849412
Finding
Underdevelopment of the macula lutea.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVChédiak-Higashi syndrome
Follow this link to review classifications for Chédiak-Higashi syndrome in Orphanet.

Professional guidelines

PubMed

Zamani R, Shahkarami S, Rezaei N
Allergol Immunopathol (Madr) 2021;49(2):178-190. Epub 2021 Mar 1 doi: 10.15586/aei.v49i2.61. PMID: 33641308
Lozano ML, Rivera J, Sánchez-Guiu I, Vicente V
Orphanet J Rare Dis 2014 Aug 18;9:132. doi: 10.1186/s13023-014-0132-6. PMID: 25129365Free PMC Article
Haddad E, Le Deist F, Blanche S, Benkerrou M, Rohrlich P, Vilmer E, Griscelli C, Fischer A
Blood 1995 Jun 1;85(11):3328-33. PMID: 7756666

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Penn EB Jr, Goudy SL
Otolaryngol Clin North Am 2015 Feb;48(1):137-51. doi: 10.1016/j.otc.2014.09.010. PMID: 25439552
Mártinez-García M, Montoliu L
J Dermatol 2013 May;40(5):319-24. doi: 10.1111/1346-8138.12170. PMID: 23668539
Grønskov K, Ek J, Brondum-Nielsen K
Orphanet J Rare Dis 2007 Nov 2;2:43. doi: 10.1186/1750-1172-2-43. PMID: 17980020Free PMC Article
Dell'Angelica EC, Mullins C, Caplan S, Bonifacino JS
FASEB J 2000 Jul;14(10):1265-78. doi: 10.1096/fj.14.10.1265. PMID: 10877819

Diagnosis

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Otolaryngol Clin North Am 2015 Feb;48(1):137-51. doi: 10.1016/j.otc.2014.09.010. PMID: 25439552
Grønskov K, Ek J, Brondum-Nielsen K
Orphanet J Rare Dis 2007 Nov 2;2:43. doi: 10.1186/1750-1172-2-43. PMID: 17980020Free PMC Article

Therapy

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Valera MC, Kemoun P, Cousty S, Sie P, Payrastre B
J Oral Pathol Med 2013 Feb;42(2):115-24. Epub 2012 May 15 doi: 10.1111/j.1600-0714.2012.01151.x. PMID: 22583386
Kumar P, Rao KS, Shashikala P, Chandrashekar HR, Banapurmath CR
Indian J Pediatr 2000 Aug;67(8):595-7. doi: 10.1007/BF02758492. PMID: 10985003
Barak Y, Nir E
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Prognosis

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Autophagy 2022 Mar;18(3):496-517. Epub 2021 Aug 19 doi: 10.1080/15548627.2021.1943177. PMID: 34130600Free PMC Article
Mozafari R, Rajabnia M, Naleini SN
Arch Iran Med 2019 Nov 1;22(11):673-674. PMID: 31823635
Donmez FY, Agildere AM
Neurol Sci 2015 Sep;36(9):1603-9. Epub 2015 Apr 18 doi: 10.1007/s10072-015-2212-3. PMID: 25894844
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Clinical prediction guides

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Expert Rev Respir Med 2019 Oct;13(10):951-967. Epub 2019 Aug 21 doi: 10.1080/17476348.2019.1654377. PMID: 31394045
Shirazi TN, Snow J, Ham L, Raglan GB, Wiggs EA, Summers AC, Toro C, Introne WJ
Orphanet J Rare Dis 2019 May 6;14(1):101. doi: 10.1186/s13023-019-1049-x. PMID: 31060595Free PMC Article
Ji X, Chang B, Naggert JK, Nishina PM
Adv Exp Med Biol 2016;854:745-50. doi: 10.1007/978-3-319-17121-0_99. PMID: 26427484
Kaplan J, De Domenico I, Ward DM
Curr Opin Hematol 2008 Jan;15(1):22-9. doi: 10.1097/MOH.0b013e3282f2bcce. PMID: 18043242
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Recent systematic reviews

de Arruda JAA, Sousa-Neto SS, Abreu LG, Schuch LF, Souza VG, Alves TVL, Martins-Andrade B, Shetty SS, Monteiro JLGC, Mendonça EF, Mesquita RA, Callou G
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