Disease Profile

Griscelli syndrome

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset






Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease


Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype


X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.


X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder


Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.


Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.


Not applicable


Other Names (AKA)

Griscelli disease


The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 381

Griscelli syndrome (GS) is a rare cutaneous disease characterized by a silvery-gray sheen of the hair and hypopigmentation of the skin, which can be associated to primary neurological impairment (type 1), immunologic impairment (type 2) or be isolated (type 3).

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.

Clinical description
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.

Diagnostic methods
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.

Differential diagnosis
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
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.

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

Management and treatment
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.

Visit the Orphanet disease page for more resources.


This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
80%-99% of people have these symptoms
Hypopigmented skin patches
Patchy loss of skin color
Premature graying of hair
Early graying
Premature graying
Premature greying
Premature hair graying

[ more ]

Silver-gray hair
Silver-gray hair color
Silvery-gray hair

[ more ]

White hair
30%-79% of people have these symptoms
Abnormal circulating lipid concentration
Abnormality of neutrophils
Decreased circulating antibody level
Decreased immune function
Decreased blood leukocyte number
Low white blood cell count

[ more ]

Swollen lymph nodes
Reduced tendon reflexes
Low platelet count
5%-29% of people have these symptoms
Abnormal eyebrow morphology
Abnormality of the eyebrow
Abnormal eyelash morphology
Abnormal eyelashes
Abnormality of the eyelashes
Eyelash abnormality

[ more ]

Accumulation of fluid in the abdomen
Bone marrow hypocellularity
Bone marrow failure
Cranial nerve paralysis
Global developmental delay
Liver inflammation
Enlarged liver
Too much cerebrospinal fluid in the brain
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific

[ more ]

Iris hypopigmentation
Light eye color
Yellow skin
Yellowing of the skin

[ more ]

Muscular hypotonia
Low or weak muscle tone
Involuntary, rapid, rhythmic eye movements
Pedal edema
Fluid accumulation in lower limbs
Lower leg swelling

[ more ]

Pyloric stenosis
Short stature
Decreased body height
Small stature

[ more ]

Involuntary muscle stiffness, contraction, or spasm
Increased spleen size


Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference contains information on Griscelli syndrome. This website is maintained by the National Library of Medicine.

In-Depth Information

  • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) lists the subtypes and associated genes for Griscelli syndrome in a table called Phenotypic Series. Each entry in OMIM includes a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.