CHEDIAK-HIGASHI sindrome
GeneReviews CHS
Clinical characteristics
Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism (OCA), immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, a lymphoproliferative infiltration of the bone marrow and reticuloendothelial system. All affected individuals including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) develop neurologic findings during early adulthood.
Diagnosis/testing
Ophthalmologic findings, history of recurrent or severe infections, and abnormal platelet aggregation studies should prompt evaluation for CHS. Diagnosis is based on identification of abnormal WBC granules on blood smear. LYST is the only gene known to be associated with CHS.
Management
Treatment of manifestations: Initial chemoimmunotherapy followed by transition to continuation therapy for the accelerated phase; allogenic HSCT as soon as possible to cure hematologic and immunologic defects; platelet transfusions as needed for serious bleeding; corrective lenses to improve visual acuity; treatment by rehabilitation specialists for neurologic complications.
Prevention of secondary complications: Prompt aggressive use of antibiotics and antiviral agents for bacterial and viral illnesses; routine immunizations; intravenous DDAVP prior to invasive procedures to help control bleeding.
Surveillance: Yearly ophthalmologic examinations. For atypical or adolescent- or adult-onset CHS: annual abdominal ultrasound examination for hepatosplenomegaly; complete blood count (CBC) for cytopenias; monitoring for liver dysfunction; and measurement of serum ferritin concentration and soluble interleukin-2 receptor.
Agents/circumstances to avoid: Nonsteroidal anti-inflammatory drugs, which can exacerbate the bleeding tendency.
Genetic counseling
CHS is inherited in an autosomal recessive manner. When both parents are heterozygous, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal diagnosis of CHS is possible if the pathogenic variants have been identified in the family.
