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Griscelli Syndrome Type 3 (GS Restricted to Hypopigmentation)

Clinical Features and Genetic Patterns

Silvery-gray hair in Griscelli type 2
Photo courtesy of Pigment International Opens in new window

GS3, the third form of GS Opens in new window, is characterized by the fair skin at birth of CHH and the other forms of GS followed by bronzed skin after sun exposure.

Children can be referred because of unspecific complaints of failure to gain weight or recurrent tonsillitis and then noticed to have silver-gray hair, eyebrows, and eyelashes.

Clinically, GS3-associated albinism is indistinguishable from that described in the other forms of GS.

Skin biopsy and light microscopic examination reveals the same pattern as GS1 Opens in new window and GS2 Opens in new window.

Microscopic analysis of hair shafts show the characteristic features of GS, i.e., the presence of large clumps of pigment in the hair shaft.

Most importantly, longitudinal follow-up reveals that phenotypic presentation is restricted to hypopigmentation, without any immune or neurological manifestation.

Gene Description

GS3 is caused by mutations Opens in new window in the gene that encodes melanophilin (Mlph) (SLAC2A/MLPH gene), the orthologue of the gene mutated in leaden mice.

It has also been shown that an identical phenotype can result from the deletion of the MYOVA F-exon, an exon with a tissue-restricted expression pattern.

The protein Mlph links the function of myosin Va and the GTP-Rab27 a protein in the melanosome without additional functions: this explains why expression in GS3 is restricted to the characteristic hypopigmentation.

In GS3 the Mlph is unable to associate with Rab27a, either transiently over expressed or endogenously expressed in melanocytes.

See also:
  1. Aksu G, Kutekculer N, Genel F, Vergin C, Omowaire B (2003) Griscelli syndrome without hemophagocytosis in an eleven-year-old girl: expanding the phenotypic spectrum of Rab27A mutations in humans. Am J Med Genet A 116:329-333.
  2. Anikster Y, Huizing M, Anderson PD, Fitzpatrick DL, Klar A, Gross-Kieselstein E, Berkun Y, Shazberg G, Gahl WA, Hurvitz H (2002) Evidence that Griscelli syndrome with neurological involvement is caused by mutations in Rab27A, not Myo5a. Am J Hum Genet 71:407-414.
  3. Arico M, Xecca M, Santoro N, Caselli D, Maccario R, Danesino C, de Saint Basile G, Locatelli F (2002) Successful treatment of Griscelli syndrome with unrelated donor allogenic hematopoietic stem cell transplantation. Bone Marrow Transplant 29: 995-998.
  4. Bahadoran P, Ortonne JP, Ballotti R, de Saint-Basile G (2003b) Comment on Elejalde syndrome and relationship with Griscelli syndrome. Am J Med Genet 166A:408-409.
  5. Elejalde BR, Holguin J, Valencia A, Gilbert EF, Molina J, Marin G, Arango LA (1979) Mutations affecting pigmentation in man: I. Neuroectodermal melanosomal disease. Am J Med Genet 3: 65-80.
  6. Fukuda M (2005) Versatile role of Rab27 in membrane trafficking: focus on the Rab27 effector families. J Biochem 137:9-16.
  7. Griscelli C, Durandy A, Guy-Grand D, Daguillard F, Herzog C, Pruneiras M (1978) A syndrome associating partial albinism and immunodeficiency. Am J Med 65: 691-702.
  8. Huizing M, Anikster Y, Gahl WA (2002) Reply to Menasche et al. Am J Hum Genet 71:1238.
  9. Ivanovich J, Mallory S, Storer T, Ciske D, Ciske D, Hing A (2001) 12-year-old male with Elejalde syndrome (neuroectodermal melanolysomal disease). Am J Med Genet 98:313-316.
  10. Mamishi S, Modarressi MH, Pourakbari B, Tamizifar B, Mahjoub F, Fahimzad A, Alyasin S, Bemanian MH, Hamidiyeh AA, Fazlollahi MR, Ashrafi MR, Iaseian A, Khotaei G, Yeganeh M, Parvaneh N (2008) Analysis of RAB27A Gene in Griscelli Syndrome type 2: Novel Mutations Including a Deletion Hotspot. J Clin Immunol Mar 19.
  11. Mancini AJ, Chan LS, Paller AS (1998) Partial albinism with immunodeficiency: Griscelli syndrome. Report of a case and review of the literature. J Am Acad Dermatol 38:295-300.
  12. Manglani M, Adhvaryu K, Seth B (2004) Griscelli syndrome – a case report. Indian Pediatr 41:734-737.
  13. Menasche G, Pastural E, Feldman J, Certain S, Ersoy F, Dupuis S, Wulfrant N, Bianci D, Fisher A, Le Deist F, de Saint Basile G (2000) Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat Genet 25: 173-176.
  14. Menasche G, Fisher A, de Saint Basile G (2002) Griscelli syndrome types 1 and 2. Am J Hum Genet 71: 1237-1238.
  15. Menasche G, HoCh, Sanal O, Feldmann J, Tezcan I, Ersoy F, Houdusse A, Fischer A, de Saint Basile G (2003) Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). J Clin Invest 112: 450-456.
  16. Elejalde BR, Valencia A, Gilbert EF, Marin G, Molina J, Holguin J (1977) Neuro-ectodermal melanolysosomal disease: an autosomal recessive pigment mutation in man. Am J Hum Genet 29:39A (abstract).
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