Griscelli syndrome

autorecessive

Griscelli syndrome is a rare genetic disorder characterized by a distinctive silver-gray hair, immunodeficiency, and neurological abnormalities. It is an autosomal recessive condition, meaning that an individual must inherit two copies of the defective gene, one from each parent, to be affected by the disorder.

Classification

Griscelli syndrome is classified into three types based on the specific gene mutations and the clinical manifestations:

• Type 1 (GS1) is caused by mutations in the MYO5A gene and is primarily associated with severe neurological impairment.
• Type 2 (GS2) results from mutations in the RAB27A gene and is characterized by immunodeficiency and an increased risk of developing hemophagocytic lymphohistiocytosis (HLH).
• Type 3 (GS3) is due to mutations in the MLPH gene and typically presents with milder symptoms, primarily affecting the skin and hair.

Symptoms

The symptoms of Griscelli syndrome can vary depending on the type but generally include:

• Silver-gray hair with large clumps of pigment in the hair shaft
• Light skin pigmentation
• Recurrent infections due to immunodeficiency (particularly in GS2)
• Neurological abnormalities such as developmental delay, hypotonia, and seizures (particularly in GS1)
• Hemophagocytic lymphohistiocytosis (HLH) in GS2, which is a severe, life-threatening condition

Diagnosis

Diagnosis of Griscelli syndrome is based on clinical evaluation, family history, and genetic testing to identify mutations in the MYO5A, RAB27A, or MLPH genes. Microscopic examination of hair samples can reveal characteristic pigment clumps.

Treatment

There is no cure for Griscelli syndrome, and treatment is primarily supportive and symptomatic. Management may include:

• Antibiotics and antifungal medications to treat infections
• Immunosuppressive therapy for HLH
• Physical therapy and other supportive measures for neurological symptoms
• Bone marrow transplantation may be considered in severe cases, particularly for GS2 with HLH

Prognosis

The prognosis for individuals with Griscelli syndrome varies depending on the type and severity of symptoms. GS1 and GS2 are generally associated with a poorer prognosis due to severe neurological impairment and life-threatening HLH, respectively. GS3 typically has a better prognosis with milder symptoms.

Related Pages

• Autosomal recessive disorder
• Immunodeficiency
• Neurological disorder
• Hemophagocytic lymphohistiocytosis
• Genetic testing