Diagnostic Considerations
Other considerations include postinflammatory hypopigmentation, poliosis, and leukemia. [19]
The diagnosis of Chédiak-Higashi syndrome (CHS) should be considered in individuals with pigment dilution defects of the hair, skin, or eyes; congenital or transient neutropenia; immunodeficiency; and otherwise unexplained neurologic abnormalities or neurodegeneration.
Differential Diagnoses
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Cross syndrome
Cross syndrome is manifested by hypopigmentation, ocular defects, and severe developmental delay reflecting extensive CNS involvement.
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Deficiency of endosomal adaptor p14
Clinical features include partial albinism, short stature, congenital neutropenia, and lymphoid deficiency. Neutrophils show altered azurophilic granule ultrastructure and less-than-normal microbicidal function of phagosomes, in contrast to the giant inclusions seen in neutrophils in CHS.
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Familial hemophagocytic lymphohistiocytosis (FLH)
FLH is characterized by proliferation and infiltration of hyperactivated macrophages and T lymphocytes manifesting as acute illness with prolonged fever, cytopenias, and hepatosplenomegaly. Onset is typically within the first few months of life and, on occasion, in utero, although later-childhood or adult onset is more common than previously suspected. Neurologic abnormalities that may be present initially or may develop later include increased intracranial pressure, irritability, neck stiffness, hypotonia, hypertonia, convulsions, cranial nerve palsies, ataxia, hemiplegia, quadriplegia, blindness, and coma. Rash and lymphadenopathy are less common. Other findings include liver dysfunction and bone marrow hemophagocytosis.
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Hermansky-Pudlak syndrome (HPS) is characterized by OCA and a bleeding diathesis secondary to absent platelet-dense bodies. Of the at least nine subtypes of HPS, HPS2 (caused by pathogenic variants in AP3B1) most closely resembles CHS.
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Oculocutaneous albinism
The four types of oculocutaneous albinism (OCA1, OCA2, OCA4, and XLOA) all feature visual impairment and varying degrees of iris/retinal depigmentation. Except in individuals with XLOA, in whom skin and hair pigment may be normal, the characteristic skin and hair findings vary from complete absence of pigment to reduced pigment.
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Vici syndrome
A small number of individuals with cutaneous hypopigmentation, combined immunodeficiency, agenesis of the corpus callosum, bilateral cataracts, and cleft lip and palate have been described. Cognitive impairment, seizures, and severe respiratory infections were observed.
