Griscelli syndrome

Definition

Griscelli syndrome is a rare, sometimes fatal disorder that associates partial albinism with immunodeficiency. Partial albinism is characterized by a partial lack of melanin (pigment) in the eyes, hair, and skin. The partial albinism found in patients with Griscelli syndrome is caused by an abnormal melanosome distribution. Immunodeficiency refers to an immune system in which resistance to infection is lowered.

Description

In addition to having silvery hair, most people with Griscelli syndrome develop hemophagocytic syndrome, which causes some blood cells in the body to engulf and destroy other blood cells. Hemophagocytic syndrome leads to death unless the patient undergoes a bone marrow transplant.

Some people with Griscelli syndrome are severely impaired neurologically but have no apparent immune abnormalities. Neurologic problems may be spasticity (in which a patient has uncontrolled muscular contractions), rigidity (in which a patient is inflexible or stiff), and convulsions. Through 1994 only 19 patients were reported in the medical literature as having the disorder.

Genetic profile

Griscelli syndrome is an autosomal recessive disorder that sometimes occurs in children with parents who are related by blood. There is evidence that the disorder is caused by mutations in the gene that encodes myosin VA, a protein in muscle tissue. (The gene encoding myosin VA is MYO5A.) The gene associated with Griscelli syndrome has been mapped to the long end ofchromosome 15 at location 15q21. A second gene, RAB27A, maps very close to the same region (15q21) as MYO5A.

Demographics

Both males and females are born with Griscelli syndrome.

Signs and symptoms

Griscelli syndrome causes pigmentary dilution of the skin and hair, and clumps of pigment in hair shafts. Griscelli syndrome also causes an accumulation of melanosomes in melanocytes.

People with Griscelli syndrome may also have frequent infections in which pus is present, fever, an abnormal decrease in the number of white blood cells, and a reduction in the number of platelets in the blood.

Diagnosis

Griscelli syndrome can be diagnosed in fetuses in the womb by microscopically examining the hair shaft. After birth, patients are diagnosed with Griscelli syndrome based on the signs and symptoms.

Griscelli syndrome is similar to Chediak-Higashi syndrome . For example, both are autosomal recessive disorders in which partial albinism and immunodeficiency are associated. And patients with either disorder are likely to have frequent infections.

However, patients with Chediak-Higashi syndrome are likely to have giant granules in their leukocytes, a type of white blood cell. And leukocyte-specific protease activity is typically low in patients with Chediak-Higashi syndrome, and typically normal in patients with Griscelli syndrome.

Treatment and management

In patients who have hemophagocytic syndrome associated with Griscelli syndrome, treatment may be in the form of bone marrow transplantation.

Prognosis

The prognosis for babies with Griscelli syndrome is poor without bone marrow transplantation.

Resources

PERIODICALS

Bahadoran, P., et al. "Rab27a. A Key to Melanosome Transport in Human Melanocytes." Journal of Cell Biology 152 (February 19, 2001): 843-50.

Durandy, A., et al. "Prenatal Diagnosis of Syndromes Associating Albinism and Immune Deficiencies (Chediak-Higashi Syndrome and Variant)." Prenatal Diagnosis 13 (1993): 13-20.

Gogus, S., et al. "Griscelli Syndrome: Report of Three Cases." Pediatric Pathology and Laboratory Medicine 15 (1995): 309-319.

Griscelli, C., et al. "A Syndrome Associating Partial Albinism and Immunodeficiency." American Journal of Medicine 65 (1978): 691-702.

Hurvitz, H., et al. "A Kindred with Griscelli Disease: Spectrum of Neurological Involvement." European Journal of Pediatrics 152 (1993): 402-405.

Klein, C., et al. "Partial Albinism with Immunodeficiency (Griscelli Syndrome)." Journal of Pediatrics 125 (1994): 886-895.

Mancini, A. J., L. S. Chan, and A. S. Paller. "Partial Albinism with Immunodeficiency: Griscelli Syndrome: Report of a Case and Review of the Literature." Journal of the American Academy of Dermatology 38 (1998): 295-300.

Menasche, G. E., et al. "Mutations in RAB27A Cause Griscelli Syndrome Associated with Haemophagocytic Syndrome." Nature Genetics 25 (2000): 173-176.

Pastural, E., et al. "Griscelli Disease Maps to Chromosome 15q21 and Is Associated with Mutations in the Myosin-Va Gene." Nature Genetics 16 (1997): 289-292.

Pastural, E., et al. "Two Genes Are Responsible for Griscelli Syndrome at the Same 15q21 Locus." Genomics 63 (2000): 299-306.

ORGANIZATIONS

Genetic Alliance. 4301 Connecticut Ave. NW, #404, Washington, DC 20008-2304. (800) 336-GENE (Helpline) or (202) 966-5557. Fax: (888) 394-3937 info@geneticalliance. <http://www.geneticalliance.org>.

WEBSITES

"Griscelli Syndrome." Online Mendelian Inheritance in Man. <www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=214450>.

Sonya Kunkle