|Year : 2019 | Volume
| Issue : 2 | Page : 102-104
Griscelli syndrome 3: a rare and mild variant
Mudita Gupta, Reena K Sharma, Sandhya Kumari, Saru Thakur
Department of Dermatology, Venereology and Leprosy, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
|Date of Web Publication||19-Dec-2019|
Senior Resident Reena K Sharma
Department of Dermatology, Venereology and Leprosy, Indira Gandhi Medical College, Shimla, Himachal Pradesh
Source of Support: None, Conflict of Interest: None
Griscelli syndrome is a multisystemic disorder. It is of three types with a common feature of pigmentary dilution. The clinical types depend on the gene involved leading to a varied presentation ranging from only pigmentary dilution and excellent prognosis in type 3 to a severe disease with multisystem involvement in type 2. Type 3 is the least reported variant. We describe a 23-year-old male with sporadic presence of light-colored skin and silver gray hair.
Keywords: Griscelli syndrome, pigmentary dilution, silver hair
|How to cite this article:|
Gupta M, Sharma RK, Kumari S, Thakur S. Griscelli syndrome 3: a rare and mild variant. Pigment Int 2019;6:102-4
| Introduction|| |
Griscelli syndrome (GS) is an autosomal recessive disease first described by Claude Griscelli and Michel Prunieras in 1978. On the basis of genes involved and because of the phenotype, it is of three types: GS1, GS2, and GS3. Pigmentary dilution due to defective melanosome transport is the common feature. There are less than 150 cases of GS reported till date; GS2 is the most common but there are no more than 15 cases of GS3 reported. We are presenting a rare variant of GS in a 23-year-old male presenting as pigmentary dilution only, with no systemic involvement.
| Case report|| |
A 23-year-old male presented with gray hair and light-colored skin since birth. There was no evidence of photosensitivity, abnormal bleeding, recurrent infections, fever, jaundice, seizures, developmental delay, or any neurological involvement. Child was born to nonconsanguineous parents, by normal delivery. There was no family history of similar problem. Height, weight, and genetic, and intellectual development was normal. On systemic examination, eyes and ears were within normal limits. Iris was brown colored. There was generalized dilution of skin color with gray hair present over scalp, eye brow, eye lashes, body hair, and axillary and pubic hair [Figure 1]. Brown patches of persistent tanning were present over sun-exposed sites on face. Hemoglobin was 12.4 g% and total leukocyte count was 7000/mm3; peripheral smear showed normal red blood cells, granulocytes, and platelets. Routine biochemical investigations were within normal limits. On light microscopy of hair, there was clump of pigmentation mainly in the medulla and specs of the cortex [Figure 2]. A final diagnosis of GS3 was made and the patient was counseled for the benign prognosis of the disease and advised regular follow-up.
|Figure 1 (A) Silver gray hair on scalp and face with pigmentary dilution of facial skin and tanning on cheeks. (B) Silver gray eye lashes and eye brows. (C) Silver gray hair over axilla. (D) Silver gray hair over pubic area.|
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|Figure 2 Melanin deposits in clumps in Griscelli syndrome under light microscope (40×).|
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| Discussion|| |
Melanogenesis is a multistep process starting with the synthesis of melanin, and then sorting of melanin proteins into melanosome followed by transport of this cargo to dendritic tips of melanocytes and finally to keratinocytes. Defect in either step may manifest as hypomelanosis. Regulation of protein trafficking is by adapter protein 3 and biogenesis of lysosome-related organelle complex (melanosome, platelet-dense granules and lytic granules of cytotoxic lymphocytes, and natural killer cells). In diseases like Heřmanský–Pudlák syndrome and Chediak Higashi, defective trafficking leads not only to pigmentary dilution but also to altered immunity, bleeding disorders, and giant organelles (melanosome, neutrophil, and platelet). Melanosome transport is shown in [Figure 3]. Defective transport of melanosome from center of melanocyte to dendritic tip and thus into keratinocyte is seen in GS.
|Figure 3 Melanosome transport from center to dendritic tip occurs along microtubule. The movement of melanosome is bidirectional, and kinesins and dyneins work in opposite direction. Myosin Va (myoVa) is a motor protein that attaches to melanosomes through interaction with linker protein melanophilin (mlph) and Rab27a. The tripartite complex helps in melanosome transport and membrane trafficking to keratinocyte. Defect in various components of tripartite complex leads to different variants of Griscelli syndrome with a common feature of perinuclear accumulation of melanosomes.|
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GS is a rare autosomal recessive disorder manifesting as pigmentary dilution of skin and hair. Along with pigmentary changes, other systemic involvement is present depending upon the type of GS and hence the gene involved and the defective product synthesis [Figure 3]. GS is of three types: GS1 due to myosin Va (myoVa) deficiency has associated neurological involvement presenting as primary neurological impairment, seizure, developmental delay, mental retardation, and neuromuscular or vision abnormality. Elejalde syndrome and GS1 are similar and are thought to be allelic. GS2 is the most common and the most serious variant of GS caused by Rab27a mutation, which leads to defective exocytosis of cytotoxic granules from T cells and natural killer cells with accelerated T-cell and macrophage activation. GS3 is characterized by hypomelanosis with no immunological and neurological manifestation. It is due to melanophilin (mlph) defect or deletion of exon F terminal at myoVa tail domain of melanocyte. Prognosis in GS3 is good and no treatment is required. Defective tripartite protein complex (Rab27a–mlph–myoVa) formation leads to inability of melanosomes to be connected to the actin network.
As the defect is in melanosome transfer, so clumps of melanin aggregation with areas of absent pigmentation occur giving hair a silver gray hue with road dividing line like pigmentation diagnostic of GS. Smith et al. reported that although there are other investigations like electron microscopy, polarized microscopy, skin biopsy, and gene study but light microscopic examination of hair is sufficient for diagnosing GS. Hair in Chediak Hegashi shows similar clumps of melanin but they are quite small. In GS, capacity to tan on sun exposure is retained because melanocyte number and melanin production is normal.
GS3 is a milder but rarer form of melanin transport disorder that can be easily diagnosed by light microscopy of hair and has no associated morbidity.
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Conflicts of interest
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[Figure 1], [Figure 2], [Figure 3]