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To date, approximately 150 cases have been reported, predominantly in Turkish and Mediterranean populations. GS type 2 appears to be the most common of the three known types, while GS type 3 is the least common.

GS occurs in infancy to childhood. In addition to the silvery-gray sheen of the hair and the light-colored skin, GS type 1 patients present with delayed motor development, intellectual disability and hypotonia. GS type 2 patients have the same hypopigmentation features but in association with immune pathology. Patients exhibit a lymphocyte cytotoxic defect resulting in an uncontrolled T-lymphocyte and macrophage-activation syndrome, also known as hemophagocytic syndrome (HLH), in which activated T cells and macrophages infiltrate the lymph nodes and other organs (including the brain), producing hemophagocytosis. Patients with GS type 2 can present neurological symptoms due to brain infiltration by the activated hematopoietic cells. In GS type 3 patients, hypopigmentation of the skin and hair is the only feature.

GS type 1 is caused by a mutation in the myosin Va (MYO5A) gene located on chromosome 15q21 and likely corresponds to Elejalde disease. GS type 2 is caused by mutations in the RAB27A encoding gene. Myosin-5a and RAB27A genes have been localized to the same chromosomal 15q21 region and encode for proteins which are key effectors of intracellular vesicular transport. Myosin Va regulates organelle transport in both melanocytes and neuronal cells, whereas RAB27A, regulates exocytic pathways, especially the cytotoxic granule exocytosis. The cytotoxic defect caused by RAB27A mutations is responsible for the hemophagocytic syndrome observed. GS type 3 is due to mutations in the MLPH gene, a gene encoding melanophilin, which forms a protein complex with Rab 27a and myosin Va, and participates in melanosome transport in melanocytes.

The diagnosis of the three types of GS can be established by the clinical signs and light microscopic examination, evidencing large clumps of pigment in hair shafts and the accumulation of mature melanosomes in melanocytes. A decrease in T and NK lymphocyte degranulation and cytotoxicity characterize GS type 2. No immunological or cytotoxic defects have been observed in GS type 1 or 3. Thus, based on the patient's clinical and biological features, sequencing of the corresponding causative gene allows confirmation of the type of GS.

GS can be distinguished from Chediak-Higashi syndrome by the lack of giant granules in granulocytes of GS patients. The differential diagnosis of GS type 1 also includes Elejalde disease.

Antenatal diagnosis of GS type 1 and 2 can be performed through chorionic villus sampling by the sequencing of the MYO5A or RAB27A gene, respectively.

GS is an autosomal recessive disorder and genetic counseling informing affected couples of a 25% risk of having an affected child is possible.

Treatment for GS type 1 is only symptomatic. In GS type 2, the hemophagocytic syndrome is often fatal and the only cure is hematopoietic stem cell transplantation (HSCT). Currently there is no specific management for GS type 3.

If not treated by HSCT, the prognosis for long-term survival in GS type 2 is relatively poor, with many patients not surviving the first decade. The prognosis of GS type 1 is good. GS type 3 should be better considered as a pigmentation phenotype rather than a pathology with a prognosis similar to the control population.