OMIM ID:
Chédiak-Higashi Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The ocular hypopigmentation and visual function deficits in Chédiak-Higashi syndrome resembles that of other types of albinism. The iris has transillumination defects and the retina is hypopigmented. Patients are photophobic and often have nystagmus. Due to the early mortality of many patients, vision is difficult to measure, but is said to range from normal to near normal. Hair bulb incubations studies show normal pigmentation.
A subset of patients with later onset of disease has been reported to have optic atrophy, thinning of the nerve fiber layer, and a central scotoma.
Systemic Features
This is a form of albinism with other systemic features such as adenopathy, hepatosplenomegaly, neutropenia, and susceptibility to infection (especially gram positive organisms). The hypopigmentation is evident at birth but may be patchy. The hair has been described as having a blue-green metallic sheen. It may also be sparse. Patients have an increased risk of leukemia and lymphoma-like disease. Peripheral sensory-motor neuropathy and ataxia are common in older individuals. Thrombocytopenia can lead to easy bruising and extensive bleeding. Neutrophils are often few in number and deficient in chemotactic and bacterial activity. Pyoderma and peridontitis can be severe. Survival without treatment is between 3 and 4 years but those who survive eventually develop lymphohistiocytic infiltration of major organs, bone marrow and peripheral nerves as young adults.
Giant peroxidase-positive inclusions in white blood cells are diagnostic.
Genetics
Inheritance
This is an autosomal recessive disorder caused by mutations in the LYST gene (1q42.1-q42.2) causing defects in vesicle trafficking.
Hermansky-Pudlak syndrome (214500) is another form of hypopigmentation with serious systemic manifestations.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.