|Year : 2021 | Volume
| Issue : 1 | Page : 63-65
Griscelli syndrome Type 3 in three non-identical siblings
Vivek Kumar Dey, Animesh Saxena, Somya Sharma, Anil Gour
Department of Dermatology, People's College of Medical Sciences and RC, Bhopal, Madhya Pradesh, India
|Date of Submission||01-Jul-2019|
|Date of Acceptance||21-Apr-2021|
|Date of Web Publication||29-Jun-2021|
410, Gram Sihora, Kurwai, Vidisha, Madhya Pradesh
Source of Support: None, Conflict of Interest: None
Griscelli syndrome (GS) is a fatal autosomal recessive condition characterized by genetic mutation in the intracellular melanosome transport system leading to congenital partial albinism with neurological and/or immunological involvement. It is classified into three subtypes. We present here a case of a 13-year-old girl along with her two siblings (7-year-old male and 9-year-old female) who presented with complaints of gradual onset of pigmentation of the skin with silvery grey hair, eyebrows, and eyelashes since birth. All three cases were diagnosed as GS Type 3 on the basis of clinical presentation, family history, absence of any systemic abnormality, and characteristic microscopic findings of the hair shaft and skin biopsy. To the best of our knowledge, this is the first-ever report of three non-identical siblings of GS Type 3, which is a rare syndrome. GS type 3 needs no active intervention except for regular follow-up.
Keywords: Griscelli syndrome, melanosomes, pigmentation
|How to cite this article:|
Dey VK, Saxena A, Sharma S, Gour A. Griscelli syndrome Type 3 in three non-identical siblings. J Mahatma Gandhi Inst Med Sci 2021;26:63-5
|How to cite this URL:|
Dey VK, Saxena A, Sharma S, Gour A. Griscelli syndrome Type 3 in three non-identical siblings. J Mahatma Gandhi Inst Med Sci [serial online] 2021 [cited 2022 Nov 26];26:63-5. Available from: https://www.jmgims.co.in/text.asp?2021/26/1/63/319844
| Introduction|| |
Griscelli syndrome (GS) is a fatal autosomal recessive condition characterized by genetic mutation in the intracellular melanosome transport system leading to congenital partial albinism with neurological and/or immunological involvement, was first reported in two unrelated patients in 1978 by Griscelli et al. It is classified into three subtypes with type 1 due to mutation in the MYO5A gene and associated severe primary neurological impairment, the second type due to mutation in RAB27A gene, type 3 due to mutation in melanophilin gene and it is restricted to only hypopigmentation defect.,,,
| Case Report|| |
A 13-year-old girl along with her two siblings (7-year-old male and 9-year-old female) came to our dermatology department with complaints of gradual onset of pigmentation of the skin with silvery gray hair, eyebrows, and eyelashes since birth [Figure 1].
On cutaneous examination, the index case had silvery grey hair over the scalp, eyebrows, and eyelashes. Silvery gray sheen in hair was not clearly perceptible because she had applied henna. Bronze tan hyperpigmentation over face with numerous, well-defined hypopigmented macules ranging from 0.2 to 1.0 cm over face trunk and extremities were seen. Teeth and nails appear normal [Figure 2].
The index case had three siblings. Her eldest brother and both parents were completely unaffected. Both younger siblings had similar complaints.
On cutaneous examination, they both had silvery grey hair over the scalp, eyebrows, and eyelashes with bronze tan hyperpigmentation over the face.
The younger male sibling had dense peri-ocular pigmentation and multiple pinpoint hypopigmented macules scattered over the face [Figure 3].
Her 9-year-old sister also had multiple freckles over her face [Figure 4].
|Figure 4: Bronze tan hyperpigmentation with multiple freckles over the face|
Click here to view
All children were born out of consanguineous marriage with uneventful antenatal and perinatal periods. Their nutritional and developmental status was normal. There was no history of any prodromal symptoms or photosensitivity. After all baseline investigations hematological and biochemical test, blood culture, chest X-ray other systemic abnormality was ruled out.
All three cases showed the irregular distribution of small and large melanin granules on light microscopic examination of the hair shaft [Figure 5].
|Figure 5: Irregular distribution of melanin pigment in medullary area of the hair shaft|
Click here to view
Skin biopsy could be done only for index case which showed the irregular distribution of melanin pigment and melanocytes in the basal layer with focally larger melanocytes than normal with surrounding keratinocyte showing lack of pigment, indicating transfer block [Figure 6].
|Figure 6: Irregular distribution of melanin pigment and melanocytes in the basal layer with focally larger melanocytes than normal with surrounding keratinocyte showing lack of pigment, indicating transfer block|
Click here to view
All three cases were diagnosed with GS type 3 on the basis of clinical presentation, family history, absence of any systemic abnormality, and characteristic microscopic findings of the hair shaft and skin biopsy.
| Discussion|| |
Commonly, pigmentation defect in different types of GS occurs due to defect in the interaction of genes, encoding protein for melanosome transport.
GS type 1 has characteristic neurological involvement along with partial albinism.
GS type 2 is associated with partial albinism along with primary immunodeficiency due to impaired T-cell and natural killer cytotoxic activity which culminates into a life-threatening condition known as hemophagocytic lymphohistiocytosis which causes fever, splenomegaly, hypofibrinogenemia, hypertriglyceridemia, and hyperferritinemia, can be fatal if not treated promptly.
GS type 3 due to the defect in the MLPH gene, was defined by Menasche et al. in 2003. It has a good prognosis because it is restricted to only partial albinism, and requires no treatment. It was differentiated from Chediak-Higashi Syndrome on the basis of differences in light and electron microscopic examination of hair and skin. Since then, a little over than 60 cases of GS have been reported in the medical literature, mostly from the Turkish and Mediterranean populations. A retrospective study by Smith et al. of 322 hair samples suggested that light microscopic examination of scalp hair is an inexpensive, rapid, noninvasive, and first-line investigation, which can provide valuable diagnostic information in silvery hair syndromes.
Skin biopsy can be complementary in the case where hair shaft pigment distribution does not support the diagnosis. The various other investigations to diagnose GS are electron microscopy of hair shaft and skin, polarized microscopy (shaft looks bright with a monotonously whitish appearance), and genetic study.
| Conclusion|| |
To the best of our knowledge, this is the first-ever report of three nonidentical siblings of GS Type 3, which is a rare syndrome. GS type 3 needs no active intervention except for regular follow-up. GS3 should be differentiated from GS1, GS2, Chediak-Higashi syndrome, and Eldejalde Syndrome. Before initiating any exhaustive workup, any patient presenting with silvery hair and skin pigmentation must undergo light microscopic examination.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Griscelli C, Durandy A, Guy-Grand D, Daguillard F, Herzog C, Prunieras M. A syndrome associating partial albinism and immunodeficiency. Am J Med 1978;65:691-702.
Pastural E, Barrat FJ, Dufourcq-Lagelouse R, Certain S, Sanal O, Jabado N, et al.
Griscelli disease maps to chromosome 15q21 and is associated with mutations in the myosin-Va gene. Nat Genet 1997;16:289-92.
Ménasché G, Pastural E, Feldmann J, Certain S, Ersoy F, Dupuis S, et al.
Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nat Genet 2000;25:173-6.
Pastural E, Ersoy F, Yalman N, Wulffraat N, Grillo E, Ozkinay F, et al.
Two genes are responsible for Griscelli syndrome at the same 15q21 locus. Genomics 2000;63:299-306.
Ellul M, Calvagna V. Griscelli syndrome: A rare neonatal syndrome. Malta Med J 2006;18:21-4.
Meschede IP, Santos TO, Izidoro-Toledo TC, Gurgel-Gianetti J, Espreafico EM. Griscelli syndrome-type 2 in twin siblings: Case report and update on RAB27A human mutations and gene structure. Braz J Med Biol Res 2008;41: 839-48.
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 2003;112:450-6.
Vieira-Karuta SC, Silva IC, Almeida NA, Noronha Ld, Santos ML, Liberalesso PB. Griscelli syndrome and electroencephalography pattern. Arq Neuropsiquiatr 2008;66:420-2.
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 2005;58:1294-8.
Ridaura-Sanz C, Durán-McKinster C, Ruiz-Maldonado R. Usefulness of the skin biopsy as a tool in the diagnosis of silvery hair syndrome. Pediatr Dermatol 2018;35:780-3.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]