eMedicine Specialties > Dermatology > Diseases of Pigmentation

Griscelli Syndrome: Differential Diagnoses & Workup

Author: Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, New York Medical College-Metropolitan Hospital; Private Practice
Coauthor(s): Ann M Johnson, MD, Pediatric Radiology Fellow, Department of Radiology, The Children's Hospital of Philadelphia
Contributor Information and Disclosures

Updated: Feb 1, 2008

Differential Diagnoses

Chediak-Higashi Syndrome
Elejalde Syndrome

Other Problems to Be Considered

HLH syndrome
Familial lymphohistiocytosis (MIM 603553)
X-linked lymphoproliferative syndrome (MIM 308240)
Partial albinism and immunodeficiency syndrome (MIM 604228)
Elejalde syndrome (MIM 256710)

Workup

Laboratory Studies

  • Characteristic laboratory features include pancytopenia, hypofibrinogenemia, hypertriglyceridemia, and hypoproteinemia.
  • In GS without delayed-type cutaneous hypersensitivity and impaired natural killer cell function manifests as the ever-present immunologic abnormalities.
  • Some patients with GS have secondary hypogammaglobulinemia, impaired major histocompatibility complex–mediated cytotoxic effects, a decreased capacity of lymphocytes to trigger a mixed lymphocyte reaction, or various functional granulocytic abnormalities. One report noted low levels of immunoglobulin G2 in a patient with GS.
  • Evidence of hepatitis can be demonstrated by abnormal liver function results. Neonatal hyperbilirubinemia (peak total bilirubin 26.5 mg/dL at age 4 wk) has been reported.
  • Chromosome analysis can be performed to detect mutations in MYO5A and RAB27A.

Imaging Studies

  • Both CT and MRI are used to assess GS. Usually, findings are normal at birth. When the disease manifests, imaging findings are abnormal. Findings in the 2 variants (ie, MYO5A, RAB27A) of GS are different.
  • Isolated congenital cerebellar atrophy was observed in a patient with the MYO5A defect. No evidence of infiltration of lymphocytes is present in these patients.
  • In GS caused by RAB27A defects, CT scan can show areas of coarse calcification in the globi pallidi, left parietal white matter, and periventricular and left brachium pontis.
  • Patients with GS can manifest hypodense signals in the genu and posterior limb of the internal capsule on the right side (which is compatible with inflammatory changes), as well as posterior aspects of both thalami, together with minimal generalized atrophy. CT scanning can also suggest cell infiltration of the brain.
  • In both variants, MRI can reveal areas of increased T2 signal intensity and a focal area of abnormal enhancement in the subcortical white matter.
  • At birth, findings from long-bone plain radiography have been reported to be normal.
  • When GS manifests, abdominal ultrasonograms can show hepatosplenomegaly with intrahepatic cholestasis and absence of bile duct distension.

Other Tests

  • Transmission electron microscopy of the skin shows an accumulation of numerous normal-sized stage IV mature melanosomes in the cytoplasm of melanocytes, with virtual absence of such melanosomes in adjacent keratinocytes. These findings allow GS to be distinguished from Chediak-Higashi syndrome.
  • The peripheral blood smear shows no giant cytoplasmic granules in leukocytes. These findings allow GS to be distinguished from Chediak-Higashi syndrome.
  • Neurologic evaluations reveal cerebral lymphohistiocytic infiltration and erythrophagocytosis with nonspecific electroencephalographic patterns.24
  • Valente et al25  and Smith et al26 noted that polarized light microscopy of hair shafts aids in the differential diagnosis of Chediak-Higashi syndrome and GS.

Procedures

  • Biopsy specimens of internal organs can reveal abnormalities.
  • Liver biopsy specimens can show marked portal inflammation with focal hepatocellular necrosis.
  • Bone marrow aspiration samples can reveal slight hypocellularity with mild erythroid hyperplasia and hemophagocytosis.

Histologic Findings

The common histopathologic findings of GS include prominent, mature melanosomes in skin and hair follicle melanocytes.

GS demonstrates hyperpigmented basal melanocytes and sparse pigmentation of adjacent keratinocytes. This pathology of melanocytes and keratinocytes leads to large, clumped melanosomes in hair shafts, and, as a result, the hair has a silvery-gray sheen. These results can be highlighted in Fontana-Masson–stained sections. Light microscopy shows irregular, large aggregations of melanin pigment in hair.

Celik et al27 investigated the light and scanning electron microscopic examination of hair in persons with GS and found that the hair showed a normal cuticular pattern but nodular structures were present as abnormal findings.

More on Griscelli Syndrome

Overview: Griscelli Syndrome
Differential Diagnoses & Workup: Griscelli Syndrome
Treatment & Medication: Griscelli Syndrome
Follow-up: Griscelli Syndrome
References
[ CLOSE WINDOW ]

References

  1. Griscelli C, Prunieras M. Pigment dilution and immunodeficiency: a new syndrome. Int J Dermatol. Dec 1978;17(10):788-91. [Medline].

  2. Aslan D, Sari S, Derinöz O, Dalgiç B. Griscelli syndrome: description of a case with Rab27A mutation. Pediatr Hematol Oncol. Apr-May 2006;23(3):255-61. [Medline].

  3. Bahadoran P, Busca R, Chiaverini C, Westbroek W, Lambert J, Bille K, et al. Characterization of the molecular defects in Rab27a, caused by RAB27A missense mutations found in patients with Griscelli syndrome. J Biol Chem. Mar 28 2003;278(13):11386-92. [Medline].

  4. Bizario JC, Feldmann J, Castro FA, Ménasché G, Jacob CM, Cristofani L, et al. Griscelli syndrome: characterization of a new mutation and rescue of T-cytotoxic activity by retroviral transfer of RAB27A gene. J Clin Immunol. Jul 2004;24(4):397-410. [Medline].

  5. 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. Nov 2006;1086:66-80. [Medline].

  6. Janka GE. Familial and acquired hemophagocytic lymphohistiocytosis. Eur J Pediatr. Feb 2007;166(2):95-109. [Medline].

  7. Filipovich AH. Hemophagocytic lymphohistiocytosis and related disorders. Curr Opin Allergy Clin Immunol. Dec 2006;6(6):410-5. [Medline].

  8. Ménasché G, Ho CH, Sanal O, Feldmann J, Tezcan I, Ersoy F, et al. Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F-exon deletion (GS1). J Clin Invest. Aug 2003;112(3):450-6. [Medline].

  9. Hume AN, Collinson LM, Hopkins CR, Strom M, Barral DC, Bossi G, et al. The leaden gene product is required with Rab27a to recruit myosin Va to melanosomes in melanocytes. Traffic. Mar 2002;3(3):193-202. [Medline].

  10. Neeft M, Wieffer M, de Jong AS, Negroiu G, Metz CH, van Loon A, et al. Munc13-4 is an effector of rab27a and controls secretion of lysosomes in hematopoietic cells. Mol Biol Cell. Feb 2005;16(2):731-41. [Medline].

  11. Westbroek W, Lambert J, De Schepper S, Kleta R, Van Den Bossche K, Seabra MC, 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. Oct 2004;17(5):498-505. [Medline].

  12. Gazit R, Aker M, Elboim M, Achdout H, Katz G, Wolf DG, et al. NK cytotoxicity mediated by CD16 but not by NKp30 is functional in Griscelli syndrome. Blood. May 15 2007;109(10):4306-12. [Medline].

  13. Desnos C, Huet S, Darchen F. 'Should I stay or should I go?': myosin V function in organelle trafficking. Biol Cell. Aug 2007;99(8):411-23. [Medline].

  14. Manglani M, Adhvaryu K, Seth B. Griscelli syndrome - a case report. Indian Pediatr. Jul 2004;41(7):734-7. [Medline].

  15. Rath S, Jain V, Marwaha RK, Trehan A, Rajesh LS, Kumar V. Griscelli syndrome. Indian J Pediatr. Feb 2004;71(2):173-5. [Medline].

  16. Enders A, Zieger B, Schwarz K, Yoshimi A, Speckmann C, Knoepfle EM, et al. Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II. Blood. Jul 1 2006;108(1):81-7. [Medline].

  17. 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. May 2006;27(5):402-7. [Medline].

  18. Rajadhyax M, Neti G, Crow Y, Tyagi A. Neurological presentation of Griscelli syndrome: obstructive hydrocephalus without haematological abnormalities or organomegaly. Brain Dev. May 2007;29(4):247-50. [Medline].

  19. Ashrafi MR, Mohseni M, Yazdani S, Alizadeh H, Ramyar A, Aghamohammadi A, et al. Bilateral basal ganglia involvement in a patient with Griscelli syndrome. Eur J Paediatr Neurol. Jul 2006;10(4):207-9. [Medline].

  20. Dinakar C, Lewin S, Kumar KR, Harshad SR. Partial albinism, immunodeficiency, hypergammaglobulinemia and Dandy-Walker cyst--a Griscelli syndrome variant. Indian Pediatr. Oct 2003;40(10):1005-8. [Medline].

  21. Grønskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007;2:43. [Medline].

  22. 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. Jun 13 2007;1. [Medline].

  23. Kharkar V, Pande S, Mahajan S, Dwiwedi R, Khopkar U. Griscelli syndrome: a new phenotype with circumscribed pigment loss?. Dermatol Online J. 2007;13(2):17. [Medline].

  24. Haraldsson A, Weemaes CM, Bakkeren JA, Happle R. Griscelli disease with cerebral involvement. Eur J Pediatr. Apr 1991;150(6):419-22. [Medline].

  25. Valente NY, Machado MC, Boggio P, Alves AC, Bergonse FN, Casella E, et al. Polarized light microscopy of hair shafts aids in the differential diagnosis of Chédiak-Higashi and Griscelli-Prunieras syndromes. Clinics. Aug 2006;61(4):327-32. [Medline].

  26. 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. Dec 2005;58(12):1294-8. [Medline].

  27. Celik HH, Tore H, Tunali S, Tatar I, Aldur MM. Light and scanning electron microscopic examination of hair in Griscelli syndrome. Saudi Med J. Aug 2007;28(8):1275-7. [Medline].

  28. Mehdizadeh M, Zamani G. Griscelli syndrome: a case report. Pediatr Hematol Oncol. Oct-Nov 2007;24(7):525-9. [Medline].

  29. Köse O, Kürekçi AE, Safali M, Akin R, Köseoglu V, Tezcan I, et al. Development of in situ melanoma after allogeneic bone marrow transplantation in Griscelli syndrome type II. Pediatr Transplant. Nov 2007;11(7):792-5. [Medline].

  30. Dave S, Pudukadan D, Thappa DM. Griscelli syndrome: a rare immunodeficiency disorder with partial albinism. J Dermatol. Mar 2004;31(3):247-50. [Medline].

  31. de Saint Basile G. Griscelli syndrome. Orphanet. Available at http://www.orpha.net/data/patho/GB/uk-griscelli.pdf. Accessed March, 2001.

  32. Gögüs S, Topçu M, Küçükali T, Akçören Z, Berkel I, Ersoy F, et al. Griscelli syndrome: report of three cases. Pediatr Pathol Lab Med. Mar-Apr 1995;15(2):309-19. [Medline].

  33. Malhotra AK, Bhaskar G, Nanda M, Kabra M, Singh MK, Ramam M. Griscelli syndrome. J Am Acad Dermatol. Aug 2006;55(2):337-40. [Medline].

  34. Mancini AJ, Chan LS, Paller AS. Partial albinism with immunodeficiency: Griscelli syndrome: report of a case and review of the literature. J Am Acad Dermatol. Feb 1998;38(2 Pt 2):295-300. [Medline].

  35. Tomita Y, Suzuki T. Genetics of pigmentary disorders. Am J Med Genet C Semin Med Genet. Nov 15 2004;131C(1):75-81. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

GS, MIM 214450, partial albinism with immunodeficiency, Griscelli-Prunieras syndrome, Griscelli-Prunieras variant, Griscelli's disease, Griscelli disease

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, New York Medical College-Metropolitan Hospital; Private Practice
Noah S Scheinfeld, MD, JD, FAAD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Ann M Johnson, MD, Pediatric Radiology Fellow, Department of Radiology, The Children's Hospital of Philadelphia
Disclosure: Nothing to disclose.

Medical Editor

Julie C Harper, MD, Assistant Program Director, Assistant Professor, Department of Dermatology, University of Alabama at Birmingham
Julie C Harper, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.