Introduction Causes Classification Demographics Diagnosis Treatment
Griscelli syndrome is a rare hereditary syndrome characterised by pigmentary dilution of the skin and silver-coloured hair. There may be associated immunological or neurological problems.
Griscelli syndrome is a form of partial albinism. It is also called Griscelli-Pruniéras syndrome. Untreated, most children with Griscelli syndrome die in early childhood.
Griscelli syndrome is caused by genetic mutations leading to defective transport of melanosomes. Melanosomes are pigment granules containing melanin that are found within melanocytes. Normally, the melanosomes are moved from the centre of the melanocyte to its border so that melanin can be transferred to surrounding keratinocytes (skin cells). When transportation fails, melanosomes accumulate within the melanocyte and the skin appears pale.
There are 3 main types of Griscelli syndrome.
Type 1 Griscelli syndrome is associated with neurological dysfunction and is due to a defect in the MYO5A gene (myosin VA, myoxin). Neurological problems are often present at birth or develop in infancy. These include changes in muscle tone or paralysis, seizures, and developmental delay. Type 1 Griscelli syndrome is also called Elejalde syndrome.
Type 2 Griscelli syndrome is associated with immunological deficiency and increased risk of infection. This type is due to a defect in the RAB27A gene (a member of the RAS oncogene family). There is uncontrolled T lymphocyte and macrophage activation leading to haemophagocytic lymphohistiocytosis (HLH). HLH is a blood disorder where activated macrophages (a type of blood cell) phagoctyose (engulf) other blood cells. Reduced numbers of circulating blood cells leads to anaemia, bleeding tendency and increased risk of infection.
Type 3 Griscelli syndrome presents with partial dilution of skin and hair pigment only, without systemic problems. It is caused by mutation in either the MYO5A or MLPH (melanophilin) gene.
Additional findings in type 1 and 2 Griscelli syndrome include:
Griscelli syndrome is rare, with a prevalence of less than 1 per million. Most cases are reported in Turkish and Mediterranean populations. Griscelli syndrome is an autosomal recessive condition meaning that two defective genes are inherited, one from each parent.
Griscelli syndrome usually presents in infancy or early childhood, in most cases between the ages of 4 months and 7 years.
Griscelli syndrome should be considered in a child with silver hair, eyebrows and eyelashes, particularly if there are neurological or immune defects.
Microscopic analysis of hair shafts shows clumps of pigment. Histological examination of a skin biopsy may reveal prominent melanosomes within epidermal and hair follicle melanocytes.
In suspected Griscelli syndrome, chromosomal analysis may be performed to look for the specific gene defect.
Griscelli syndrome has been successfully treated by stem cell transplantation.
