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Griscelli syndrome type 3(GS3)

MedGen UID:
373124
Concept ID:
C1836573
Disease or Syndrome
Synonyms: GS3; Hypomelanosis with no immunologic or neurologic manifestations
SNOMED CT: Griscelli syndrome type 3 (1254947002); Hypopigmentation-immunodeficiency disease type 3 (1254947002)
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): MLPH (2q37.3)
 
Monarch Initiative: MONDO:0012220
OMIM®: 609227
Orphanet: ORPHA79478

Definition

Griscelli syndrome type 3 (GS3) is a rare autosomal recessive disorder that results in a characteristic pigmentary dilution of the skin and hair, which shows a silvery-gray sheen associated with large clumps of pigment in hair shafts and an abnormal accumulation of end-stage melanosomes in the center of melanocytes. There are no immunologic or neurologic manifestations (summary by Menasche et al., 2003). For a discussion of phenotypic and genetic heterogeneity in Griscelli syndrome, see 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.

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.

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.  https://medlineplus.gov/genetics/condition/griscelli-syndrome

Clinical features

From HPO
Abnormality of the nervous system
MedGen UID:
105425
Concept ID:
C0497552
Congenital Abnormality
An abnormality of the nervous system.
Immunodeficiency
MedGen UID:
7034
Concept ID:
C0021051
Disease or Syndrome
Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.
Silver-gray hair
MedGen UID:
322949
Concept ID:
C1836576
Finding
Hypopigmented hair that appears silver-gray.
White eyelashes
MedGen UID:
332275
Concept ID:
C1836736
Finding
White color (lack of pigmentation) of the eyelashes.
Large clumps of pigment irregularly distributed along hair shaft
MedGen UID:
870855
Concept ID:
C4025315
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGriscelli syndrome type 3
Follow this link to review classifications for Griscelli syndrome type 3 in Orphanet.

Suggested Reading

Recent clinical studies

Etiology

Al-Mayouf SM, Alreefi HA, Alsinan TA, AlSalmi G, AlRowais A, Al-Herz W, Alazami AM, Alsonbul A, Al-Mousa H
Mod Rheumatol 2021 Nov;31(6):1171-1178. Epub 2021 Feb 22 doi: 10.1080/14397595.2021.1886627. PMID: 33563058
Gironi LC, Zottarelli F, Savoldi G, Notarangelo LD, Basso ME, Ferrero I, Timeus F, Fagioli F, Maiuri L, Colombo E, Savoia P
Medicina (Kaunas) 2019 Mar 25;55(3) doi: 10.3390/medicina55030078. PMID: 30934652Free PMC Article
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
Batrani M, Thole A, Kubba A, Mahajan K
J Cutan Pathol 2018 Dec;45(12):918-922. Epub 2018 Sep 25 doi: 10.1111/cup.13342. PMID: 30129079

Diagnosis

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
Al-Mayouf SM, Alreefi HA, Alsinan TA, AlSalmi G, AlRowais A, Al-Herz W, Alazami AM, Alsonbul A, Al-Mousa H
Mod Rheumatol 2021 Nov;31(6):1171-1178. Epub 2021 Feb 22 doi: 10.1080/14397595.2021.1886627. PMID: 33563058
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
Batrani M, Thole A, Kubba A, Mahajan K
J Cutan Pathol 2018 Dec;45(12):918-922. Epub 2018 Sep 25 doi: 10.1111/cup.13342. PMID: 30129079
Nouriel A, Zisquit J, Helfand AM, Anikster Y, Greenberger S
Pediatr Dermatol 2015 Nov-Dec;32(6):e245-8. Epub 2015 Sep 4 doi: 10.1111/pde.12663. PMID: 26337734

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
Gironi LC, Zottarelli F, Savoldi G, Notarangelo LD, Basso ME, Ferrero I, Timeus F, Fagioli F, Maiuri L, Colombo E, Savoia P
Medicina (Kaunas) 2019 Mar 25;55(3) doi: 10.3390/medicina55030078. PMID: 30934652Free PMC Article
Cağdaş D, Ozgür TT, Asal GT, Tezcan I, Metin A, Lambert N, de Saint Basile G, Sanal O
Eur J Pediatr 2012 Oct;171(10):1527-31. Epub 2012 Jun 19 doi: 10.1007/s00431-012-1765-x. PMID: 22711375

Clinical prediction guides

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

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