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Griscelli disease

Orpha number ORPHA381
Synonym(s) Chédiak-Higashi-like syndrome
Griscelli-Pruniéras syndrome
Partial albinism - immunodeficiency
Prevalence <1 / 1 000 000
Inheritance
  • Autosomal recessive
Age of onset Childhood
ICD-10
  • E70.3
OMIM
UMLS -
MeSH -
MedDRA -
SNOMED CT -

Summary

Griscelli syndrome (GS) is characterised by silvery gray sheen of the hair and hypopigmentation of the skin which can be associated to neurological impairment (type 1), immunodeficiency (type 2) or be isolated (type 3). More than 60 cases have been reported so far. In addition to silvery gray sheen of the hair and light-coloured skin, GS type 1 patients present with early and severe psychomotor retardation. Patients with GS type 2 exhibit a cytotoxic defect and the appearance of an uncontrolled T-lymphocyte and macrophage-activation syndrome also known as haemophagocytic syndrome : lymph nodes and other organs (including the brain) become infiltrated by activated T cells and macrophages which phagocytize blood cells (known as hemophagocytose). Patients with Griscelli syndrome type 2 can present with neurological symptoms due to brain infiltation by the activated hematopoietic cells (hemophagocytic syndrome). Griscelli syndrome is an autosomal recessive disorder. GS type 1 is caused by a mutation in the myosin Va (MYO5A) gene located on chromosome 15q21. Griscelli syndrome type 1 likely corresponds to Elejalde syndrome (see this term). 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 triggering the hemophagocytic syndrome. GS type 3 is due to mutations in MLPH, a gene encoding melanophilin, which forms a protein complex with Rab 27a and myosin Va and participate to melanosome transport in melanocytes. Hypopigmentation of the skin and the hair is accompanied by the presence of large aggregates of pigment in hair shafts and the accumulation of mature melanosomes in melanocytes. Griscelli syndrome (GS) can be distinguished from Chediak-Higashi syndrome (see this term) by the lack of giant granules in GS granulocytes. Genetic counselling can be performed. Antenatal diagnosis of GS1 and 2 can be performed through chorionic villus sampling by the sequencing of the MYO5A or RAB27A gene, respectively. Treatment for GS type 1 is only symptomatic. In GS type 2, the hemophagocytic syndrome is often fatal, and the only cure is bone-marrow transplantation.

Expert reviewer(s)

  • Dr Geneviève DE SAINT-BASILE - CHAZELAS

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