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  Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 11  |  Issue : 5  |  Page : 799-803  

Griscelli syndrome type 3 with coexistent universal dyschromia—An uncommon association of a rare entity


1 Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar LohiaHospital, New Delhi, India
2 Department of Pathology, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar LohiaHospital, New Delhi, India

Date of Submission24-Nov-2019
Date of Decision13-Jan-2020
Date of Acceptance06-Mar-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Surabhi Sinha
Department of Dermatology, Venereology and Leprosy, Atal Bihari Vajpayee Institute of Medical Sciences and Dr. Ram Manohar Lohia Hospital, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/idoj.IDOJ_572_19

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   Abstract 


Griscelli syndrome type 3 is an autosomal recessive disorder caused by mutations in the melanophilin gene and does not have any mucocutaneous or systemic abnormalities other than a pigmentary dilution of skin and hair. We report a case of an 8-year-old girl who presented with silvery grey hair of scalp, eyebrows, eyelashes, and entire body surface with associated universal dyschromia of the skin. After establishing a definite diagnosis of Griscelli syndrome 3, the prognosis was explained and counseling was given. A review of the literature revealed only 27 cases of Griscelli syndrome type 3 in the English language of which only one case by Batrani et al. has reported an associated dyschromia. We report this case to add to the existing literature on this rare condition and to highlight the coexistence of universal dyschromia with Griscelli syndrome type 3.

Keywords: Grey hair, Griscelli syndrome, universal dyschromia


How to cite this article:
Mathachan SR, Sinha S, Malhotra P. Griscelli syndrome type 3 with coexistent universal dyschromia—An uncommon association of a rare entity. Indian Dermatol Online J 2020;11:799-803

How to cite this URL:
Mathachan SR, Sinha S, Malhotra P. Griscelli syndrome type 3 with coexistent universal dyschromia—An uncommon association of a rare entity. Indian Dermatol Online J [serial online] 2020 [cited 2020 Oct 30];11:799-803. Available from: https://www.idoj.in/text.asp?2020/11/5/799/295593




   Introduction Top


Griscelli syndrome (GS), first described by Griscelli in 1978, is a rare autosomal recessive disorder characterized by partial pigmentary dilution of skin and hair.[1] Three types of this disorder have been described with loss of function of three distinct genes.[2] The three genes together encode a tripartite protein complex mediating the melanosome transport pathway thereby distributing melanin from melanocytes to the surrounding keratinocytes. Mutation of these genes will result in perinuclear accumulation of melanosome within the melanocytes and is considered to be the hallmark of the disease.[3] Among the three subtypes of GS, types 1 and 3 are rare.[4] Here, we report a case of an 8-year-old girl who presented with silvery grey hair of scalp, eyebrows, eyelashes, and entire body surface with associated dyschromia of the skin. A review of the literature revealed only 24 cases of GS type 3 in the English language of which only one case by Batrani et al. has reported an associated dyschromia.[5]


   Case Report Top


An 8-year-old Indian girl born out of a nonconsanguineous marriage presented to our outpatient department with chief complaints of light-colored scalp and body hair along with light-colored spots distributed all over the body surface. On examination, she had silvery grey hair over the scalp (predominantly over the frontal and temporal region) and the eyebrows and eyelashes [Figure 1]. Several discrete hypopigmented macules on a background of diffuse hyperpigmentation were present all over the body surface covered with fine grey hair [Figure 2]. The hypopigmented macules were remarkably predominant over the face, trunk, and the lower limbs. The rest of the physical and systemic examination was within normal limits and no other family member was involved. There was no history of any recurrent infections or failure to thrive.
Figure 1: 8-year-old girl with silvery grey hair including eyelashes and eyebrows with dyschromia of face

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Figure 2: Hypopigmented macules with diffuse hyperpigmentation and fine grey hair on the trunk

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A trichogram revealed coarse unevenly distributed clumps of melanin pigment in the medulla of the hair shaft [Figure 3]. Skin biopsy from the hypopigmented macule revealed enlarged hyperpigmented melanocytes with sparsely pigmented adjacent keratinocytes in the basal layer of the epidermis [Figure 4]. Immunohistochemistry with HMB-45 showed an enlarged and increased number of pigment laden melanocytes [Figure 5]. Masson Fontana stain from the hyperpigmented lesion showed uniform prominence of enlarged hyperpigmented melanocytes [Figure 6] and from the hypopigmented lesion showed patchy prominence of enlarged hyperpigmented melanocytes [Figure 7]. The hematological and neurological evaluation was done from the respective departments and was normal. Further, the patient was also referred to the department of pediatrics for the assessment for any developmental/growth delay and was found normal. On the basis of clinical examination, absence of neurological or immunological abnormalities, typical findings on hair trichogram and skin biopsy, a diagnosis of GS3 was made. Mutational analysis for confirmation could not be done as it was not available in our center and the patient could not afford it elsewhere.
Figure 3: Whole-mount of patient hair showing large unevenly distributed clumps of melanin pigment in the medulla of the hair shaft (unstained ×400)

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Figure 4: Histopathology of both hypo- and hyperpigmented lesion showing enlarged hyperpigmented basal melanocytes with sparsely pigmented adjacent keratinocytes (H and E ×200)

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Figure 5: Human melanoma black (HMB-45) immunohistochemical highlights enlarged pigment-laden melanocytes which appear increased in number

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Figure 6: Mason-Fontana stain on hyperpigmented lesion showing uniform prominence of enlarged hyperpigmented melanocytes (H and E ×200)

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Figure 7: Mason Fontana stain on hypopigmented lesion showing patchy prominence of enlarged hyperpigmented melanocytes (H and E ×200)

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   Discussion Top


GS is a rare autosomal recessive congenital disorder characterized by a mutation in genes encoding RAB27A/melanophilin/myosin 5a tripartite protein complex which is required for the capture of matured melanosomes by the peripheral actin network of the melanocytes and their transfer to the surrounding keratinocytes.[6] Mutation in each member of this complex will result in three different forms of GS with skin and hair hypopigmentation as a common feature of all subtypes. GS type 1 caused by a mutation in the myosin 5a gene is characterized by neurological manifestations in addition to skin and hair changes. There is no curative treatment for GS type 1 other than palliative care.[2] GS type 2 is caused by the RAB27A gene mutation. Predominant features of GS2 are immunological dysregulation and life-threatening hemophagocytic syndrome caused by activated T cells and macrophages infiltrating various organs (including the brain) and causing massive tissue damage, organ failure, pancytopenia, and (in the absence of immunosuppressive treatment) death thereby requiring early intervention. Bone marrow transplantation is the only curative treatment for this condition.[2]

GS3 is caused by mutations in the melanophilin gene and does not have any mucocutaneous or systemic abnormalities other than a pigmentary dilution of skin and hair; thus, it has a good prognosis and needs little or no treatment.[7] In addition to melanophilin gene mutation, two cases of GS3 with MYO5a F-exon deletion have been reported.[8],[9] Close differential diagnoses for silvery/grey hair syndromes are GS type 1 and type 2, Chediak–Higashi syndrome (CHS).[2] However, except for GS3, all other conditions are associated with variable hematological, neurological, and immunological abnormalities, which were absent in our patient. When it comes to silvery-white hair with dyschromia, familial melanopathy with gigantic melanocytes (FGM) is different, however, it is almost impossible to differentiate them without a genetic analysis and needs further scientific studies. Other differentials for the universal dyschromia in our patient are dyschromatosis universalis hereditaria (DUH) and amyloidosis cutis dyschromia. However, in cases of DUH and ACD abnormal melanocytes and grey hair are not seen as in GS3.[10] Close differential diagnosis of GS3 and dyschromia along with its clinical features, histopathology, hair microscopy, and management are given in [Table 1].[2],[5]
Table 1: Close differential diagnosis of Griscelli syndrome type 3 (GS3) and dyschromia along with its clinical features, histopathology, hair microscopy, and management[2],[5]

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Most reported cases of GS are from the Turkish and Mediterranean populations. To our knowledge, a total of 27 cases of GS3 have been reported so far.[1],[2],[3],[4],[5],[6],[7],[8],[9],[11],[12],[13],[14],[15],[16],[17] An association with dyschromia has been reported in a case report by Batrani et al. in 2018.[5] Two cases with diffuse bronze hyperpigmentation in GS3 have also been reported.[2],[7] We report this case to add to the existing literature on this rare condition and to highlight the coexistence of universal dyschromia with GS3. Cases of GS3 reported so far with associated additional features are summarized in [Table 2].[1],[2],[3],[4],[5],[6],[7],[8],[9],[11],[12],[13],[14],[15],[16],[17]
Table 2: Cases of GS3 reported so far with associated additional features

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Alonazi N, Alanazi A, Huma R, Alnemri A, Hawwari A. Griscelli syndrome type 3: A case report from Kingdom of Saudi Arabia. J Clin Case Rep 2016;6:2.  Back to cited text no. 1
    
2.
Khemka P, Kundu R, Niyogi P, Tudu J. A case of silvery hair syndrome: Griscelli syndrome. Indian J Paediatr Dermatol 2015;16:72.  Back to cited text no. 2
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3.
Westbroek W, Klar A, Cullinane AR, Ziegler SG, Hurvitz H, Ganem A, et al. Cellular and clinical report of new Griscelli syndrome type III cases. Pigment Cell Melanoma Res 2012;25:47-56.  Back to cited text no. 3
    
4.
Çaǧdaş D, Özgür TT, Asal GT, Tezcan İ, 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;171:1527-31.  Back to cited text no. 4
    
5.
Batrani M, Thole A, Kubba A, Mahajan K. Silvery hair with dyschromatosis: Griscelli syndrome type 3 or familial gigantic melanocytosis. J Cutan Pathol 2018;45:918-22.  Back to cited text no. 5
    
6.
Kaur S, Jindal N, Dayal S, Jain VK, Jairath V, Virdi S. A rare pigmentary disorder in two non-identical siblings: Griscelli syndrome–type 3. Dermatol Online J 2014;20. pii: 13030/qt4r42t43w.  Back to cited text no. 6
    
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Shah BJ, Jagati AK, Katrodiya NK, Patel SM. Griscelli syndrome type-3. Indian Dermatol Online J 2016;7:506.  Back to cited text no. 7
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8.
Sanal O, Ersoy F, Tezcan I, Metin A, Yel L, Ménasché G, et al. Griscelli disease: Genotype-phenotype correlation in an array of clinical heterogeneity. J Clin Immunol 2002;22:237-43.  Back to cited text no. 8
    
9.
Yılmaz M, Çaǧdaş D, Grandin V, Altıntaş DU, Tezcan İ, de Saint Basile G, et al. Griscelli syndrome type 3-like phenotype with MYO-5A exon-F deletion. Pediatr Allergy Immunol 2014;25:817-9.  Back to cited text no. 9
    
10.
El-Darouti MA, Fawzi SA, Marzook SA, El-Eishi NH, Abdel-Halim MR, Soliman SA. Familial gigantic melanocytosis. Int J Dermatol 2005;44:1010-5.  Back to cited text no. 10
    
11.
Al-Idrissi E, ElGhazali G, AlZahrani M, Ménasché G, Schmid JP, de Saint Basile G. Premature birth, respiratory distress, intracerebral hemorrhage, and silvery-gray hair: Differential diagnosis of the 3 types of Griscelli syndrome. J Pediatr Hematol Oncol 2010;32:494-6.  Back to cited text no. 11
    
12.
Akgun OM, Altun C, Polat GG, Yildirim C. Oral and dental findings of Griscelli syndrome type 3. Arch Clin Exp Surg 2015;4:164-7.  Back to cited text no. 12
    
13.
Nouriel A, Zisquit J, Helfand AM, Anikster Y, Greenberger S. Griscelli syndrome type 3: Two new cases and review of the literature. Pediatr Dermatol 2015;32:e245-8.  Back to cited text no. 13
    
14.
Hemalata L, Pradeep R, Siddavatam S, Benakappa A. Silvery gray hair syndromes: An insight into diagnosis. Indian J Child Health 2017;4:193-8.  Back to cited text no. 14
    
15.
Kassem HY, Ramstein C, Ginglinger E, Chouta FN, Nojavan H, Michel C. Griscelli syndrome type 3: A new case. Ann Dermatol Venereol 2018;145:785-9.  Back to cited text no. 15
    
16.
Dagnewu KY, Ayele A, Liu L, Pramanik R, Onoufriadis A, Abebe E, et al. Griscelli syndrome type 3 in Ethiopian sisters resulting from a homozygous missense mutation in MLPH. Int J Dermatol. 2020 Mar; 59(3):e55-e57.  Back to cited text no. 16
    
17.
Gupta M, Sharma RK, Kumari S, Thakur S. Griscelli syndrome 3: A rare and mild variant. Pigment Int 2019;6:102.  Back to cited text no. 17
  [Full text]  


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2]



 

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