Griscelli Syndrome Clinical Presentation
- Author: Noah S Scheinfeld, JD, MD, FAAD; Chief Editor: Dirk M Elston, MD more...
Often, the first manifestation of Griscelli syndrome that is noted is silver hair. The differential diagnosis of the disease in a patient presenting with silvery hair includes primarily Griscelli syndrome, Chediak-Higashi syndrome, and Elejalde syndrome. Not long after, the immunologic effects of Griscelli syndrome caused by mutations in RAB27A are noted. The immunologic defects of Griscelli syndrome resemble those of HLH syndrome and the X-linked lymphoproliferative syndrome. Although Hermansky-Pudlak disease is a form of albinism, it does not present with silver hair or immunologic findings like Griscelli syndrome.[29, 30]
Some patients can remain in good health, with only limited syndomes into their 20s.
The neurologic effects of Griscelli syndrome caused by defects in MYO5A usually manifest early in life and even close to birth.
Severe neurologic manifestations in Griscelli syndrome are associated with defects in the MYO5A gene. Severe neurologic symptoms are noticeable at birth without any sign of an accelerated phase. CNS disorder is stable and never regresses with time. The symptoms consist of the following:
Obstructive hydrocephalus without hematological abnormalities or organomegaly 
Bilateral basal ganglia involvement 
Absence of coordinated voluntary movements
Peripheral facial palsy
Severe retarded psychomotor development similar to that observed in Elejalde syndrome
Griscelli syndrome caused by the RAB27A mutation can also cause neurologic manifestations in association with HS (accelerated phase). Neurologic problems may be the first sign of HS (accelerated phase). Neurologic manifestations occurring in patients with Griscelli syndrome caused by the RAB27A mutation are related to lymphocyte infiltration of the CNS. These problems are not as severe as those found in Griscelli syndrome caused by MYO5A mutations.
The symptoms include hyperreflexia, seizures, signs of intracranial hypertension (eg, vomiting, altered consciousness), regression of developmental milestones, hypertonia, nystagmus, and ataxia. Psychomotor development is normal at onset, and regression of CNS signs, at least in part, can be observed during remission, although some sequelae may be irreversible.
At birth, nonspecific findings can occur that include petechiae and hepatosplenomegaly.
A history of severe infections associated with the occurrence of acute phases of uncontrolled lymphocyte and macrophage activation, so-called HS (accelerated phase), can be present in patients with mutations in RAB27A. These infections are not present in patients with mutations in MYO5A.
In 2003, Dinakar et al reported on a 6-year-old girl with Griscelli syndrome. The patient experienced perpetual infections, seizures, regression of milestones, silvery hair, and organomegaly. Her brain was affected with unusual features of a Dandy-Walker cyst, and her blood and bone marrow were also affected, manifesting hypergammaglobulinemia.
Al-Idrissi et al reported on a preterm neonate with Griscelli syndrome type 3 who presented with silvery-gray hair and eyelashes, respiratory distress, and intracerebral hemorrhage. The authors stressed the importance of early differentiation of type 3 from Griscelli syndrome type 2, which is associated with a curable (but life threatening) immune disorder.
Mutations in both MYO5A and RAB27A cause pigmentary dilution and other internal organ abnormalities.
Skin manifestations of both Griscelli syndrome variants include granulomatous skin lesions, partial albinism, and generalized lymphadenopathy. The appearance of the hair has been variably described as silvery gray, silvery, grayish golden, or dusty. The skin is usually pale, but the albinism is not complete. Kharkar et al described a phenotype of Griscelli syndrome with circumscribed pigment loss.
Liver manifestations include hepatosplenomegaly and jaundice as a result of hepatitis.
Patients can present with pallor as a result pancytopenia.
Neurologic impairments can occur as a result of CNS lymphohistiocytic infiltration with erythrophagocytosis. Upon physical examination, especially in children with mutations in MYO5A, hemiparesis, peripheral facial palsy, spasticity, seizures, psychomotor retardation, and severe retarded psychomotor development may be noted.
Ocular defects can occur in Griscelli syndrome. Partial ocular albinism has been observed in some patients with Griscelli syndrome, but retinal degeneration has not been reported in this disorder.
Akcakus et al noted Griscelli syndrome in an infant associated with asymmetric crying facies.
Rajadhyax et al noted obstructive hydrocephalus without hematological abnormalities or organomegaly in a patients with Griscelli syndrome.
Griscelli syndrome is a genetic disorder related to mutations in MYO5A and RAB27A (see Pathophysiology).
Griscelli C, Prunieras M. Pigment dilution and immunodeficiency: a new syndrome. Int J Dermatol. 1978 Dec. 17(10):788-91. [Medline].
Aslan D, Sari S, Derinoz O, Dalgic B. Griscelli syndrome: description of a case with Rab27A mutation. Pediatr Hematol Oncol. 2006 Apr-May. 23(3):255-61. [Medline].
Bahadoran P, Busca R, Chiaverini C, et al. Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome. J Biol Chem. 2003 Mar 28. 278(13):11386-92. [Medline].
Bizario JC, Feldmann J, Castro FA, et al. Griscelli syndrome: characterization of a new mutation and rescue of T-cytotoxic activity by retroviral transfer of RAB27A gene. J Clin Immunol. 2004 Jul. 24(4):397-410. [Medline].
Takagishi Y, Murata Y. Myosin Va mutation in rats is an animal model for the human hereditary neurological disease, Griscelli syndrome type 1. Ann N Y Acad Sci. 2006 Nov. 1086:66-80. [Medline].
Al-Idrissi E, ElGhazali G, Alzahrani M, et al. Premature birth, respiratory distress, intracerebral hemorrhage, and silvery-gray hair: differential diagnosis of the 3 types of Griscelli syndrome. J Pediatr Hematol Oncol. 2010 Aug. 32(6):494-6. [Medline].
Cagdas D, Ozgür TT, Asal GT, Tezcan I, Metin A, Lambert N, 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 Oct. 171(10):1527-31. [Medline].
Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr. 2007 Feb. 166(2):95-109. [Medline].
Filipovich AH. Hemophagocytic lymphohistiocytosis and related disorders. Curr Opin Allergy Clin Immunol. 2006 Dec. 6(6):410-5. [Medline].
Love PB, Patterson SS, Prose NS, Atwater AR. Griscelli syndrome associated with hemophagocytic lymphohistiocytosis. J Drugs Dermatol. 2012 Sep. 11(9):1126. [Medline].
Menasche G, Ho CH, Sanal O, et al. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). J Clin Invest. 2003 Aug. 112(3):450-6. [Medline].
Hume AN, Collinson LM, Hopkins CR, et al. The leaden gene product is required with Rab27a to recruit myosin Va to melanosomes in melanocytes. Traffic. 2002 Mar. 3(3):193-202. [Medline].
Van Gele M, Dynoodt P, Lambert J. Griscelli syndrome: a model system to study vesicular trafficking. Pigment Cell Melanoma Res. 2009 Jun. 22(3):268-82. [Medline].
Westbroek W, Lambert J, De Schepper S, et al. Rab27b is up-regulated in human Griscelli syndrome type II melanocytes and linked to the actin cytoskeleton via exon F-Myosin Va transcripts. Pigment Cell Res. 2004 Oct. 17(5):498-505. [Medline].
Gazit R, Aker M, Elboim M, et al. NK cytotoxicity mediated by CD16 but not by NKp30 is functional in Griscelli syndrome. Blood. 2007 May 15. 109(10):4306-12. [Medline].
Desnos C, Huet S, Darchen F. Should I stay or should I go?': myosin V function in organelle trafficking. Biol Cell. 2007 Aug. 99(8):411-23. [Medline].
Vincent LM, Gilbert F, Dipace JI, et al. Novel 47.5-kb deletion in RAB27A results in severe Griscelli Syndrome Type 2. Mol Genet Metab. 2010 Jun 10. [Medline].
Yılmaz M, Cağdaş D, Grandin V, Altıntaş DU, Tezcan I, de Saint Basile G, et al. Griscelli syndrome type 3-like phenotype with MYO-5A exon-F deletion. Pediatr Allergy Immunol. 2014 Oct 6. [Medline].
Cetica V, Hackmann Y, Grieve S, Sieni E, Ciambotti B, Coniglio ML, et al. Patients with Griscelli syndrome and normal pigmentation identify RAB27A mutations that selectively disrupt MUNC13-4 binding. J Allergy Clin Immunol. 2014 Oct 10. [Medline].
Manglani M, Adhvaryu K, Seth B. Griscelli syndrome - a case report. Indian Pediatr. 2004 Jul. 41(7):734-7. [Medline].
Rath S, Jain V, Marwaha RK, Trehan A, Rajesh LS, Kumar V. Griscelli syndrome. Indian J Pediatr. 2004 Feb. 71(2):173-5. [Medline].
Ramzan M, Yadav SP, Kharya G, et al. Hemophagocytic Lymphohistiocytosis in Infants: A Single Center Experience from India. Pediatr Hematol Oncol. 2014 Jan 2. [Medline].
Raghuveer C, Murthy SC, Mithuna MN, Suresh T. Silvery Hair with Speckled Dyspigmentation: Chediak-Higashi Syndrome in Three Indian Siblings. Int J Trichology. 2015 Jul-Sep. 7 (3):133-5. [Medline].
Jennane S, El Kababri M, Hessissen L, et al. [A hemophagocytic syndrome revealing a Griscelli syndrome type 2]. Ann Biol Clin (Paris). 2013 Jul-Aug. 71(4):461-4. [Medline].
Dotta L, Parolini S, Prandini A, et al. Clinical, laboratory and molecular signs of immunodeficiency in patients with partial oculo-cutaneous albinism. Orphanet J Rare Dis. 2013 Oct 17. 8:168. [Medline]. [Full Text].
Enders A, Zieger B, Schwarz K, et al. Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II. Blood. 2006 Jul 1. 108(1):81-7. [Medline].
Li W, He M, Zhou H, Bourne JW, Liang P. Mutational data integration in gene-oriented files of the Hermansky-Pudlak Syndrome database. Hum Mutat. 2006 May. 27(5):402-7. [Medline].
Cagdas D, Ozgür TT, Asal GT, Tezcan I, Metin A, Lambert N, 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 Jun 19. [Medline].
Rajadhyax M, Neti G, Crow Y, Tyagi A. Neurological presentation of Griscelli syndrome: obstructive hydrocephalus without haematological abnormalities or organomegaly. Brain Dev. 2007 May. 29(4):247-50. [Medline].
Ashrafi MR, Mohseni M, Yazdani S, et al. Bilateral basal ganglia involvement in a patient with Griscelli syndrome. Eur J Paediatr Neurol. 2006 Jul. 10(4):207-9. [Medline].
Dinakar C, Lewin S, Kumar KR, Harshad SR. Partial albinism, immunodeficiency, hypergammaglobulinemia and Dandy-Walker cyst--a Griscelli syndrome variant. Indian Pediatr. 2003 Oct. 40(10):1005-8. [Medline].
Al-Idrissi E, Elghazali G, Alzahrani M, et al. Premature Birth, Respiratory Distress, Intracerebral Hemorrhage, and Silvery-gray Hair: Differential Diagnosis of the 3 Types of Griscelli Syndrome. J Pediatr Hematol Oncol. 2010 Aug. 32(6):494-6. [Medline].
Kharkar V, Pande S, Mahajan S, Dwiwedi R, Khopkar U. Griscelli syndrome: a new phenotype with circumscribed pigment loss?. Dermatol Online J. 2007 May 1. 13(2):17. [Medline].
Gronskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007 Nov 2. 2:43. [Medline].
Akcakus M, Koklu E, Narin N, Kose M. Clinical and microscopic hair features of Griscelli syndrome associated with asymmetric crying facies in an infant. Pediatr Dev Pathol. 2007 Jun 13. 1.
Bryceson YT, Pende D, Maul-Pavicic A, et al. A prospective evaluation of degranulation assays in the rapid diagnosis of familial hemophagocytic syndromes. Blood. 2012 Mar 22. 119(12):2754-63. [Medline].
Haraldsson A, Weemaes CM, Bakkeren JA, Happle R. Griscelli disease with cerebral involvement. Eur J Pediatr. 1991 Apr. 150(6):419-22. [Medline].
Valente NY, Machado MC, Boggio P, et al. Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes. Clinics (Sao Paulo). 2006 Aug. 61(4):327-32. [Medline].
Smith VV, Anderson G, Malone M, Sebire NJ. Light microscopic examination of scalp hair samples as an aid in the diagnosis of paediatric disorders: retrospective review of more than 300 cases from a single centre. J Clin Pathol. 2005 Dec. 58(12):1294-8. [Medline].
Celik HH, Tore H, Tunali S, Tatar I, Aldur MM. Light and scanning electron microscopic examination of hair in Griscelli syndrome. Saudi Med J. 2007 Aug. 28(8):1275-7. [Medline].
Cesaro S, Locatelli F, Lanino E, et al. Hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis: a retrospective analysis of data from the Italian Association of Pediatric Hematology Oncology (AIEOP). Haematologica. 2008 Nov. 93(11):1694-701. [Medline].
Trottestam H, Beutel K, Meeths M, et al. Treatment of the X-linked lymphoproliferative, Griscelli and Chédiak-Higashi syndromes by HLH directed therapy. Pediatr Blood Cancer. 2009 Feb. 52(2):268-72. [Medline].
Mehdizadeh M, Zamani G. Griscelli syndrome: a case report. Pediatr Hematol Oncol. 2007 Oct-Nov. 24(7):525-9. [Medline].
Kose O, Kurekci AE, Safali M, Akin R, Koseoglu V, Tezcan I. Development of in situ melanoma after allogeneic bone marrow transplantation in Griscelli syndrome type II. Pediatr Transplant. 2007 Nov. 11(7):792-5. [Medline].
Navarrete CL, Araníbar L, Mardones F, Avila R, Velozo L. Cutaneous granulomas in Griscelli type 2 syndrome. Int J Dermatol. 2015 Dec 23. [Medline].