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Griscelli syndrome type 2(GS2)

MedGen UID:
357030
Concept ID:
C1868679
Disease or Syndrome
Synonyms: Griscelli syndrome with hemophagocytic syndrome; GS2; Partial albinism and immunodeficiency syndrome
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): RAB27A (15q21.3)
 
Monarch Initiative: MONDO:0011872
OMIM®: 607624
Orphanet: ORPHA79477

Definition

Griscelli syndrome type 2 (GS2) is an autosomal recessive disorder characterized by pigmentary dilution of the skin and hair, the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. Patients also have immunologic abnormalities with or without neurologic impairment (summary by Menasche et al., 2000). Some GS2 patients have been reported in whom central nervous system manifestations are the first presentation (Rajadhyax et al., 2007, Masri et al., 2008; Mishra et al., 2014; Lee et al., 2017). For a discussion of phenotypic and genetic heterogeneity of Griscelli syndrome, see Griscelli syndrome type 1 (GS1; 214450). [from OMIM]

Additional description

From MedlinePlus Genetics
Griscelli syndrome is an inherited condition characterized by unusually light (hypopigmented) skin and light silvery-gray hair starting in infancy. Researchers have identified three types of this disorder, which are distinguished by their genetic cause and pattern of signs and symptoms.

Unusually light skin and hair coloring are the only features of Griscelli syndrome type 3. People with this form of the disorder do not have neurological abnormalities or immune system problems.

Griscelli syndrome type 1 involves severe problems with brain function in addition to the distinctive skin and hair coloring. Affected individuals typically have delayed development, intellectual disability, seizures, weak muscle tone (hypotonia), and eye and vision abnormalities. Another condition called Elejalde disease has many of the same signs and symptoms, and some researchers have proposed that Griscelli syndrome type 1 and Elejalde disease are actually the same disorder.

People with Griscelli syndrome type 2 have immune system abnormalities in addition to having hypopigmented skin and hair. Affected individuals are prone to recurrent infections. They also develop an immune condition called hemophagocytic lymphohistiocytosis (HLH), in which the immune system produces too many activated immune cells called T-lymphocytes and macrophages (histiocytes). Overactivity of these cells can damage organs and tissues throughout the body, causing life-threatening complications if the condition is untreated. People with Griscelli syndrome type 2 do not have the neurological abnormalities of type 1.  https://medlineplus.gov/genetics/condition/griscelli-syndrome

Clinical features

From HPO
Hepatosplenomegaly
MedGen UID:
9225
Concept ID:
C0019214
Sign or Symptom
Simultaneous enlargement of the liver and spleen.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Hemophagocytosis
MedGen UID:
163750
Concept ID:
C0876991
Disease or Syndrome
Phagocytosis by macrophages of erythrocytes, leukocytes, platelets, and their precursors in bone marrow and other tissues.
Reduced delayed hypersensitivity
MedGen UID:
334744
Concept ID:
C1843386
Finding
Decreased ability to react to a delayed hypersensitivity skin test.
Recurrent bacterial infections
MedGen UID:
334943
Concept ID:
C1844383
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Hypopigmentation of the skin
MedGen UID:
102477
Concept ID:
C0162835
Disease or Syndrome
A reduction of skin color related to a decrease in melanin production and deposition.
Silver-gray hair
MedGen UID:
322949
Concept ID:
C1836576
Finding
Hypopigmented hair that appears silver-gray.
Accumulation of melanosomes in melanocytes
MedGen UID:
375180
Concept ID:
C1843389
Finding
Melanin pigment aggregation in hair shafts
MedGen UID:
375181
Concept ID:
C1843390
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGriscelli syndrome type 2
Follow this link to review classifications for Griscelli syndrome type 2 in Orphanet.

Professional guidelines

PubMed

Brauer N, Maruta Y, Lisci M, Strege K, Oschlies I, Nakamura H, Böhm S, Lehmberg K, Brandhoff L, Ehl S, Parvaneh N, Klapper W, Fukuda M, Griffiths GM, Hennies HC, Niehues T, Ammann S
Front Immunol 2023;14:1151166. Epub 2023 Jun 14 doi: 10.3389/fimmu.2023.1151166. PMID: 37388727Free PMC Article
Zamani R, Shahkarami S, Rezaei N
Allergol Immunopathol (Madr) 2021;49(2):178-190. Epub 2021 Mar 1 doi: 10.15586/aei.v49i2.61. PMID: 33641308
Trottestam H, Beutel K, Meeths M, Carlsen N, Heilmann C, Pasić S, Webb D, Hasle H, Henter JI
Pediatr Blood Cancer 2009 Feb;52(2):268-72. doi: 10.1002/pbc.21790. PMID: 18937330

Suggested Reading

Recent clinical studies

Etiology

Zamani R, Shahkarami S, Rezaei N
Allergol Immunopathol (Madr) 2021;49(2):178-190. Epub 2021 Mar 1 doi: 10.15586/aei.v49i2.61. PMID: 33641308
Khairoun M, Meynen F, Vercoutere W, Leavis HL
Neth J Med 2020 Apr;78(3):136-141. PMID: 32332189
Kuskonmaz B, Ayvaz D, Gokce M, Ozgur TT, Okur FV, Cetin M, Tezcan I, Uckan Cetinkaya D
Pediatr Transplant 2017 Nov;21(7) Epub 2017 Aug 23 doi: 10.1111/petr.13040. PMID: 28836324
Meeths M, Horne A, Sabel M, Bryceson YT, Henter JI
Pediatr Blood Cancer 2015 Feb;62(2):346-352. Epub 2014 Nov 8 doi: 10.1002/pbc.25308. PMID: 25382070
Sieni E, Cetica V, Mastrodicasa E, Pende D, Moretta L, Griffiths G, Aricò M
Cell Mol Life Sci 2012 Jan;69(1):29-40. Epub 2011 Oct 12 doi: 10.1007/s00018-011-0835-y. PMID: 21990010Free PMC Article

Diagnosis

Khemka P, Bhattacharyya R, Ray S, Mukherjee M
J Paediatr Child Health 2016 Apr;52(4):465. doi: 10.1111/jpc.12925. PMID: 27145514
Meeths M, Horne A, Sabel M, Bryceson YT, Henter JI
Pediatr Blood Cancer 2015 Feb;62(2):346-352. Epub 2014 Nov 8 doi: 10.1002/pbc.25308. PMID: 25382070
O'Mahony J, Shroff M, Banwell B
Neuroimaging Clin N Am 2013 May;23(2):321-36. Epub 2013 Jan 23 doi: 10.1016/j.nic.2012.12.010. PMID: 23608693
Wong L, Yano S
JAMA 2012 Aug 8;308(6):617-8. doi: 10.1001/jama.2012.8136. PMID: 22871872
Sieni E, Cetica V, Mastrodicasa E, Pende D, Moretta L, Griffiths G, Aricò M
Cell Mol Life Sci 2012 Jan;69(1):29-40. Epub 2011 Oct 12 doi: 10.1007/s00018-011-0835-y. PMID: 21990010Free PMC Article

Therapy

Yamada S, Maruyama Y, Saito S, Komori K, Morokawa H, Okura E, Hirabayashi K, Furui Y, Kurata T, Nishioka M, Fukuyama T, Sakashita K, Nakazawa Y
Pediatr Hematol Oncol 2024 May;41(4):296-300. Epub 2023 Oct 31 doi: 10.1080/08880018.2023.2273880. PMID: 37906298
Groß M, Speckmann C, May A, Gajardo-Carrasco T, Wustrau K, Maier SL, Panning M, Huzly D, Agaimy A, Bryceson YT, Choo S, Chow CW, Dückers G, Fasth A, Fraitag S, Gräwe K, Haxelmans S, Holzinger D, Hudowenz O, Hübschen JM, Khurana C, Kienle K, Klifa R, Korn K, Kutzner H, Lämmermann T, Ledig S, Lipsker D, Meeths M, Naumann-Bartsch N, Rascon J, Schänzer A, Seidl M, Tesi B, Vauloup-Fellous C, Vollmer-Kary B, Warnatz K, Wehr C, Neven B, Vargas P, Sepulveda FE, Lehmberg K, Schmitt-Graeff A, Ehl S
J Allergy Clin Immunol 2022 Jan;149(1):388-399.e4. Epub 2021 May 24 doi: 10.1016/j.jaci.2021.05.007. PMID: 34033843
Sefsafi Z, Hasbaoui BE, Kili A, Agadr A, Khattab M
Pan Afr Med J 2018;29:75. Epub 2018 Jan 25 doi: 10.11604/pamj.2018.29.75.12353. PMID: 29875956Free PMC Article
Hamidieh AA, Pourpak Z, Yari K, Fazlollahi MR, Hashemi S, Behfar M, Moin M, Ghavamzadeh A
Pediatr Transplant 2013 Aug;17(5):487-91. Epub 2013 May 29 doi: 10.1111/petr.12092. PMID: 23714271
Pachlopnik Schmid J, Moshous D, Boddaert N, Neven B, Dal Cortivo L, Tardieu M, Cavazzana-Calvo M, Blanche S, de Saint Basile G, Fischer A
Blood 2009 Jul 2;114(1):211-8. Epub 2009 Apr 29 doi: 10.1182/blood-2009-02-207845. PMID: 19403888

Prognosis

Castaño-Jaramillo LM, Lugo-Reyes SO, Cruz Muñoz ME, Scheffler-Mendoza SC, Duran McKinster C, Yamazaki-Nakashimada MA, Espinosa-Padilla SE, Saez-de-Ocariz Gutierrez MDM
Scand J Immunol 2021 Jun;93(6):e13034. Epub 2021 Mar 20 doi: 10.1111/sji.13034. PMID: 33660295
Kuskonmaz B, Ayvaz D, Gokce M, Ozgur TT, Okur FV, Cetin M, Tezcan I, Uckan Cetinkaya D
Pediatr Transplant 2017 Nov;21(7) Epub 2017 Aug 23 doi: 10.1111/petr.13040. PMID: 28836324
Khemka P, Bhattacharyya R, Ray S, Mukherjee M
J Paediatr Child Health 2016 Apr;52(4):465. doi: 10.1111/jpc.12925. PMID: 27145514
Meeths M, Horne A, Sabel M, Bryceson YT, Henter JI
Pediatr Blood Cancer 2015 Feb;62(2):346-352. Epub 2014 Nov 8 doi: 10.1002/pbc.25308. PMID: 25382070
Emanuel PO, Sternberg LJ, Phelps RG
Skinmed 2007 May-Jun;6(3):147-9. doi: 10.1111/j.1540-9740.2007.05783.x. PMID: 17483661

Clinical prediction guides

Cetinkaya PG, Cagdas D, Gumruk F, Tezcan I
J Pediatr Hematol Oncol 2020 Aug;42(6):e434-e439. doi: 10.1097/MPH.0000000000001803. PMID: 32324696
Ridaura-Sanz C, Durán-McKinster C, Ruiz-Maldonado R
Pediatr Dermatol 2018 Nov;35(6):780-783. Epub 2018 Oct 18 doi: 10.1111/pde.13624. PMID: 30338556
Meeths M, Horne A, Sabel M, Bryceson YT, Henter JI
Pediatr Blood Cancer 2015 Feb;62(2):346-352. Epub 2014 Nov 8 doi: 10.1002/pbc.25308. PMID: 25382070
Cetica V, Hackmann Y, Grieve S, Sieni E, Ciambotti B, Coniglio ML, Pende D, Gilmour K, Romagnoli P, Griffiths GM, Aricò M
J Allergy Clin Immunol 2015 May;135(5):1310-8.e1. Epub 2014 Oct 11 doi: 10.1016/j.jaci.2014.08.039. PMID: 25312756Free PMC Article
Menasche G, Feldmann J, Houdusse A, Desaymard C, Fischer A, Goud B, de Saint Basile G
Blood 2003 Apr 1;101(7):2736-42. Epub 2002 Nov 21 doi: 10.1182/blood-2002-09-2789. PMID: 12446441

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