Griscelli syndrome

background

Griscelli syndrome (GS) is a rare genetic disorder that primarily affects the skin and hair. GS belongs to a group of conditions known as albinism and is named after Claude Griscelli, who first described this syndrome. This group of conditions is marked by decreased or absent pigment (coloring) in the skin, hair, and eyes. In some cases, albinism causes eye problems, including decreased pigment in the iris.
Albinism is caused by mutations in genes that encode for making the pigment melanin, which provides color to hair, skin, and eyes. Melanin also absorbs ultraviolet light from the sun in order to protect the skin. Because melanin is absent or decreased in GS, affected individuals are at increased risk of skin damage caused by the sun, including skin cancer.
People with GS tend to have a milder form of albinism characterized by pale skin and silvery gray hair at birth. In addition, they tend to develop clumps of pigment at the hairline and in melanocytes, a type of skin cell. Individuals with GS may also be prone to developing neurological and immune system disorders. There are several types of GS, which include Griscelli syndrome types 1, 2, and 3.
GS is caused by mutations in one of three genes. These are the RAB27A,MYO5A, and MLPH genes, which provide instructions for the proper production and transport of melanin.
GS is inherited, or passed down among family members, as an autosomal recessive trait. Individuals receive two copies of most genes, one from the mother and one from the father. To inherit an autosomal recessive trait, an individual must inherit two recessive copies of the causative gene.
GS is extremely rare, and its exact prevalence is unknown. There have been about 60 cases reported worldwide and fewer than 10 reported in the scientific literature in the United States. Internationally, GS has been reported in people of Indian, Turkish, and other Mediterranean descent. GS appears to affect males and females in equal numbers.
The prognosis for those with GS is generally poor. Without bone marrow transplantation, individuals with this syndrome tend to die by five years of age.

Related Terms

Albinism, Griscelli disease, Griscelli syndrome type 1, Griscelli syndrome type 2, Griscelli syndrome type 3, Griscelli syndrome with neurologic impairment, Griscelli syndrome-cutaneous and neurological type, Griscelli-Prunieras syndrome, Griscelli-Prunieras variant, Griscelli's disease, GS, GS1, GS2, GS3, partial albinism, partial albinism and primary neurologic disease without hemophagocytic syndrome, partial albinism with immunodeficiency.

types of the disease

Griscelli syndrome type 1: Griscelli syndrome type 1 (GS1) is also known as Griscelli syndrome with primary neurologic impairment and without immunologic impairment. This form of the disease is caused by mutation in the MYO5A gene, which encodes for making the myosin5a (MYO5A) protein (also known as the myosinVA or MYOVA protein). The MYO5A protein is responsible for the movement of organelles (vesicles) within the cell that carry the pigment melanin. Defects in this gene result in pigment dilution. The neurologic effects of GS caused by defects in the MYO5A gene usually appear very early in life. Severe neurologic manifestations in GS are associated with defects in the MYO5A gene. Severe neurologic symptoms are noticeable at birth, without any sign of an accelerated phase or regression over time. Symptoms include seizures, slow development of motor function, absence of coordinated voluntary movements, hypotonia (low muscle tone), and various structural abnormalities. Infections are not present in individuals with a MYO5A defect.
Griscelli syndrome type 2: Griscelli syndrome type 2 (GS2) is also known as Griscelli syndrome with immune impairment. This form of the disease is caused by mutations in the RAB27A gene, which provides instructions for making the GTP-binding protein RAB27A. The RAB27A protein is responsible for the movement of organelles (tiny organs) within the cell that carry the pigment melanin. Defects in this gene result in pigment dilution. GS caused by the RAB27A mutation can also cause neurologic manifestations in association with GS in the accelerated phase. Neurologic problems may be the first sign of GS in the accelerated phase. Neurologic manifestations occurring in patients with GS caused by the RAB27A mutation may not be as severe as those found in GS caused by MYO5A mutations. Symptoms include seizures, hypotonia, and intracranial hypertension, which is characterized by vomiting and altered states of consciousness. A history of severe infections associated with uncontrolled lymphocyte and macrophage activation can be present in patients with mutations in the RAB27A gene. GS2 typically progresses rapidly and may cause death by 1-4 years of age.
Griscelli syndrome type 3: Griscelli syndrome type 3 (GS3) is characterized by decreased melanin but no immune system or neurologic problems. This form of the disease is caused by mutations in the melanophilin gene (also known as MLPH), which provides instructions for making the melanophilin protein. This protein serves as a link between melanosome-bound RAB27A and the motor protein MYO5A. Together, these defects decrease the transport of melanin. Some researchers suggest that GS3 may also be caused by certain mutations in the MYO5A gene.