Includes:
— Griscelli syndrome type 1 – MYO5A gene
Also known as: Griscelli syndrome with neurologic impairment; Partial albinism and primary neurologic disease without hemophagocytic syndrome; Griscelli syndrome, cutaneous and neurologic type. OMIM#214450 https://omim.org/entry/214450
— Griscelli syndrome type 2 – RAB27A gene
Also known as: Griscelli syndrome with hemophagocytic syndrome; Partial albinism and immunodeficiency syndrome; PAID syndrome. OMIM#607624 https://omim.org/entry/607624
1. The disease:
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, not included here, because lack of immunodeficiency). 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.
2. The symptoms:
Infants are often initially asymptomatic at birth except for the loss of pigmentation of hair, skin and eyes. GS occurs in infancy to childhood. Lack of early signs or symptoms does not exclude the diagnosis.
- GS type 1: In addition to the silvery-gray sheen of the hair and the light-colored skin, patients present with motor development delay, intellectual disability and hypotonia.
- GS type 2: patients have the same hypopigmentation features but in association with immune abnormality. 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.
- GS type 3: patients have only hypopigmentation of the skin and hair (not included in Baby Detect).
3. Actions to take in case of early diagnosis:
- Infants with a positive genetic test (having 2 mutations or 2 copies of a single mutations in the MYO5A or RAB27A gene) should continue breastfeeding
- Infants with a positive genetic test should have a light microscopic examination, evidencing large clumps of pigment in hair shafts and the accumulation of mature melanosomes in melanocytes; and an immunologic detailed investigation, to identify a decrease in T and NK lymphocyte degranulation and cytotoxicity as expected in GS 2.
- GS is a lifelong condition that requires lifetime management and regular follow-up with an immunology specialist and a multidisciplinary approach to care, including dermatology, pediatrics and genetics.
- Infections should be treated promptly with antibiotics or antivirals and exposure to infectious agents avoided.
- The haematological and immunological manifestations can be treated by allogeneic hematopoietic stem cell transplantation (HSCT) upon diagnosis. HSCT is more successful when performed before the accelerated phase, but does not alter progression of neurological dysfunction.
- Management of the acceleration phase involves combination therapy with etoposide, dexamethasone, and cyclosporine.
- Desmopressin can be used for bleeding prophylaxis.
- Standard therapeutic measures should be adopted to improve visual acuity and to manage neurological manifestations. Patients should use sunscreen and wear protective UV sunglasses.
- Genetic counselling is highly recommended for family planning and evaluation of at-risk family members.
4. For more information:
Biblio:
- https://www.ncbi.nlm.nih.gov/books/NBK5188/
- Cağdaş D, Ozgür TT, Asal GT, et al. Griscelli syndrome types 1 and 3: analysis of four new cases and long-term evaluation of previously diagnosed patients. Eur J Pediatr. 2012; 171 (10): 1527-1531. PMID: 22711375.