Silvery Hair Research Articles

Primary cutaneous T-cell lymphoma not otherwise specified (NOS) uncovering a novel RAB27A variant in Griscelli syndrome type 2.

Griscelli syndrome type 2 (GS2) is a rare, autosomal recessive disorder that typically emerges during childhood. It manifests with partial albinism, silvery hair, immunodeficiency and hemophagocytic lymphohistiocytosis predisposition (HLH). Our findings suggest that lymphoproliferative disorders, including cutaneous lymphomas, should be considered part of the dermatological spectrum of GS2. While GS2 has previously been diagnosed in adults presenting with HLH, our observations indicate that HLH is not an inevitable outcome, even in patients who survive into their fifth decade of life.

Unveiling a rare co-occurrence: Marinesco-Sjogren syndrome and Griscelli syndrome type 3 with novel mutations in a child presenting with cataract – A unique case report

This case report describes a child with the coexistence of Marinesco-Sjögren syndrome (MSS) and Griscelli syndrome type 3 (GS3). A 9-year-old female with developmental delay and silvery hair had bilateral cataract and esotropia. Isolated finding of silvery hair was found in family members. Light microscopy features of the hair shaft were typical of Griscelli syndrome. Confirmation of GS3 was done by genetic sequencing, which also revealed SIL1 gene mutation, seen in MSS. This case underscores the intricacy of clinical findings and highlights the importance of genetic analysis in achieving an accurate diagnosis.

Successful use of emapalumab in refractory hemophagocytic lymphohistiocytosis in a child with Chédiak–Higashi syndrome: a case report

BackgroundHemophagocytic lymphohistiocytosis is a life-threatening disease heralded by fever, cytopenia, hepatosplenomegaly, and multisystem organ failure. Its association with genetic mutations, infections, autoimmune disorders, and malignancies is widely reported.Case presentationA 3-year-old male Arab Saudi patient with insignificant past medical history and parental consanguinity presented with abdominal distension of moderate severity and persistent fever despite receiving antibiotics. This was accompanied by hepatosplenomegaly and silvery hair. The clinical and biochemical profiles were suggestive of Chédiak–Higashi syndrome with hemophagocytic lymphohistiocytosis. The patient received the hemophagocytic lymphohistiocytosis-2004 chemotherapy protocol and had multiple hospital admissions mainly due to infections and febrile neutropenia. After achieving the initial remission, the patient’s disease reactivated and did not respond to reinduction with the hemophagocytic lymphohistiocytosis-2004 protocol. Due to the disease reactivation and intolerance of conventional therapy, the patient commenced emapalumab. The patient was successfully salvaged and underwent an uneventful hematopoietic stem cell transplantation.ConclusionsNovel agents such as emapalumab can be helpful for the management of refractory, recurrent, or progressive disease, while avoiding the toxicities of conventional therapy. Due to a paucity of available data on emapalumab, additional data are needed to establish its role in hemophagocytic lymphohistiocytosis treatment.

Silvery Hair with Immunodeficiency: A Comparative clinical brief of Griscelli Syndrome Type II and Chediak Higashi Syndrome

Silvery Hair with Immunodeficiency: A Comparative clinical brief of Griscelli Syndrome Type II and Chediak Higashi Syndrome

Griscelli Syndrome in Skin of Color: A Trichoscopic Perspective.

Griscelli syndrome (GS) is a very rare autosomal recessive disorder, belongs to group of "silvery hair syndromes" which includes Chediak-Higashi syndrome (CHS) and Elejalde syndrome. Hair light microscopy helps in the differentiation of GS and CHS, as both manifest with clinical features. Trichoscopy is useful in the diagnosis of many hair shaft disorders. Here, authors describe the trichoscopic features of GS in skin of color. This was an observational study conducted in a private dermatology clinic and in a tertiary care hospital. A total of 5 cases of suspected GS were referred by pediatrician. Consent was obtained. The demographic data in terms of age, gender, consanguinity, and clinical history was documented. Trichoscopic examination was performed with FotoFinder videodermoscope with 20× magnification, the clinical images were captured with Medicam 1000. Trichoscopy showed large and irregular pigment clumps in 4 cases. One case demonstrated hypopigmentation of hair without pigment clumps [Figure 3a]. Trichoscopy showed large and irregular pigment clumps in 4 cases. One case demonstrated hypopigmentation of hair without pigment clumps. Trichoscopy shows characteristic features GS. It is a useful method when facility for light or polarized microscope is unavailable.

Case series on Silvery Hair Syndromes: Single Center Experience.

Background:Silvery Hair Syndromes (SHS), an autosomal recessive inherited disorder, includes Chediak–Higashi syndrome (CHS), Griscelli syndrome (GS), Hermansky–Pudlak syndrome (HPS), and Elejalde syndrome. Associated immunological and neurological defects and predilection for hemophagocytic lymphohistiocytosis (HLH) makes them a distinctive entity in pediatric practice. Thorough clinical examination, bedside investigations such as peripheral blood smear (PBS) and hair microscopy, and bone marrow (BM) examination are inexpensive and reliable diagnostic tools.Methods:We report 12 cases with SHS (CHS, n = 06; GS, n = 04; HPS, n = 02).Results:8 out of 12 SHS children (CHS-05, GS-03) presented with HLH. Out of 5 cases of CHS with HLH, 2 died, 3rd is stable post-chemotherapy; 4th completed chemotherapy, underwent matched related hematopoietic stem cell transplant (HSCT), and is stable 8 months off treatment. The 5th child completed chemotherapy and is in process of transplant. One CHS child without HLH is thriving without any treatment. Of the 4 GS cases, 3 presented with HLH and received chemotherapy (HLH 2004 protocol). One lost follow-up after initial remission; another had recurrence 7 months off treatment and discontinued further treatment. The third child had recurrence 1.5 years after initial chemotherapy; HLH 2004 protocol was restarted followed by HSCT from matched sibling donor; is currently well, 2.5 years post-transplant. One child with GS had neurological features with no evidence of HLH and did not take treatment. Of 2 children with HPS, one presented with severe sepsis and the other with neurological problems. They were managed symptomatically.Conclusion:In SHS with HLH, chemotherapy followed by allogeneic hematopoietic stem cell transplantation is a promising curative option.

Diagnostic and therapeutic caveats in Griscelli syndrome.

Griscelli syndrome (GS) is a rare autosomal recessive disease with characteristic pigment distribution, and there are currently 3 types according to the underlying genetic defect and clinical features. We present the case of a girl born from consanguineous parents who presented with predominant neurologic symptoms, silvery hair and granulomatous skin lesions. Cerebral magnetic resonance revealed diffuse white matter lesions, and central nervous system (CNS) lymphocytic infiltration was suspected. The patient underwent haematopoietic stem cell transplantation with graft failure and autologous reconstitution. She developed elevated liver enzyme with a cholestatic pattern. Multiple liver biopsies revealed centrilobular cholestasis and unspecific portal inflammation that improved with immunomodulatory treatment. She was revealed to have an impaired cytotoxicity in NK cells and a decreased expression of RAB27A. However, no variants were found in the gene. All types of GS present with pigment dilution and irregular pigment clumps that can be seen through light microscopy in hair and skin biopsy. Dermic granulomas and immunodeficiency with infectious and HLH predisposition have been described in GS type 2 (GS2). Neurologic alterations might be seen in GS type 1 (GS1) and GS type 2 (GS2), due to different mechanisms. GS1 presents with neurologic impairment secondary to myosin Va role in neuronal development and synapsis. Meanwhile, GS2 can present with neurologic impairment secondary to SNC HLH. Clinical features and cytotoxicity might aid in differentiating GS1 and GS2, especially since treatment differs.

Neuro-Regression in a Child with Silvery Hair.

Neuro-Regression in a Child with Silvery Hair.

The color of skin: gray diseases of the skin, nails, and mucosa

Gray diseases are a group of skin disorders characterized mainly by gray discoloration with or without involving the mucous membranes and nails. These diseases may be hereditary or acquired. Some of the better-known hereditary entities are dermal melanocytosis, incontinentia pigmenti, hypomelanosis of Ito, hemochromatosis, ochronosis, and silvery hair syndrome. Acquired diseases with gray coloring include late-stage organ failure, lichen planus pigmentosus, erythema dyschromicum perstans, and drug reactions. The discoloration is due to either increased epidermal and or dermal melanin or dermal deposition of a chromogen or a combination of both. Investigations are directed to determining the underlying medical condition and a skin biopsy is usually unnecessary. Likewise, treatment is directed mainly toward the underlying medical disease. Although bleaching (lightening) agents may diminish the discoloration, better results may be obtained from using a Q-switched laser and intense pulsed light, either alone or in combination with topical agents.

Association of Anti N-methyl-D-aspartate (NMDA) Receptor Encephalitis with Chediak-Higashi Syndrome

Neurological manifestations of Chediak-Higashi syndrome mainly includeperipheral neuropathy, ataxia, tremors, cranial nerve palsies, intellectual decline and seizures. A 2 years 10 month old girl with silvery hair syndrome presented with sub-acute onset behavioral issues, ataxia and multiple type abnormal movements. Cerebrospinal fluid examination was positive for Anti NMDA receptor antibodies. Hair shaft examination and peripheral blood film findings were suggestive of Chediak Higashi syndrome. Anti NMDA receptor encephalitis may be associated with Chediak Higashi Syndrome.

Usefulness of the skin biopsy as a tool in the diagnosis of silvery hair syndrome.

Silvery hair syndrome is a rare, autosomal-recessive entity characterized by silvery gray hair, eyebrows, and eyelashes and may be associated or not with immunologic or neurologic alterations. Two main types have been recognized: Chediak-Higashi syndrome and Griscelli syndrome. Hair shaft examination under light microscopy has been a useful tool to differentiate Chediak-Higashi syndrome from Griscelli syndrome, although distribution of melanin varies according to hair color related to ethnicity. The objective was to compare the pattern of melanin in the skin and with the pattern of melanin distribution in the hair shaft. Sixteen patients with silvery hair syndrome were selected (Chediak-Higashi syndrome 5, Griscelli syndrome 11). The distribution of melanin granules in skin and hair shafts was compared and correlated with clinical diagnoses. Chediak-Higashi syndrome was characterized by small granules of melanin uniformly distributed throughout the thickness of the epidermis. Griscelli syndrome was characterized by an irregular pigment distribution in the epidermal basal layer with large and dense granules alternating with areas lacking melanin pigment. In two cases, study of the hair was not conclusive, but the skin showed the characteristic pattern of Griscelli syndrome. Skin biopsy is a useful tool in differentiating Chediak-Higashi syndrome from Griscelli syndrome and as a complementary study in cases in which hair shaft pigment distribution does not support the diagnosis, especially in patients with fair hair. The distribution of melanin granules in the skin correlates with that observed in the hair shaft, allowing Chediak-Higashi syndrome to be differentiated from Griscelli syndrome, at any age.

Griscelli Syndrome Type 3: A Case Report from Kingdom of Saudi Arabia

Griscelli syndrome (GS) is a rare autosomal recessive disorder characterized by partial albinism. GSis a rare condition; its prevalence is unknown. Type 2 appears to be the most common of the three known types. The three different types of GS are caused by mutations in three different genes. Patients with GS type 1 have primary central nervous system dysfunction, resulting from mutations in the MYO5A gene. Type 2 patients commonly develop hemophagocytic. Lymphohistiocytosis, caused by mutations in the RAB27A gene, and type 3 have only partial albinism resulting from mutations in the MLPH. While hematopoietic stem cell transplantation is lifesaving in type 2, no specific therapy is required for types 1 and 3. Patients with GS types 1 and 3 are very rare. To date, 12 patients with similar presentation of GS-3 as our case have been reported. About 20 GS type 1 patients, including the patients described as Elejalde syndrome, have been reported. We report a 11 years old child with type 3 GS, referred to our clinic for partial albinism, healthy otherwise, having only pigmentary dilution; silvery gray hair, eye brows, and eyelashes. Though GS type1 and 2 have been reported in the literature; however reports on GS type 3 from Saudi Arabia are very scanty. In communities with high incidence of consanguinity possibility of GS should be kept in mind.

Elejalde Syndrome: The Silvery Hair Syndrome

Elejalde Syndrome is a rare autosomal recessive disorder. The characteristic features are silvery hair and profound central nervous system dysfunction. Unevenly distributed melanin granules are observed on hair analysis.

Neuroimaging findings in Griscelli syndrome type 2 with primary neurological presentation

We report the radiologic findings in two children with Griscelli syndrome who presented mainly with neurologic findings. Both children were born to consanguineous parents, had normal birth and developmental histories; both had silvery gray hair from the time of birth. The first child presented with symptoms of increased intracranial pressure and cerebellar ataxia; the second child with cerebellar ataxia alone. Microscopic examination of the hair in both the children demonstrated the characteristic melanin clumps suggestive of Griscelli syndrome. Magnetic resonance imaging of the brain in the first child demonstrated multifocal white matter hyperintensities in the cerebrum and diffuse white matter hyperintensities in the cerebellum, with intense contrast enhancement. In the second child, signal changes were confined to the cerebellum and spinal cord. The first child succumbed to rapidly progressive increased intra-cranial pressure; partial autopsy revealed necrotizing lesions involving the cerebellar hemispheres bilaterally which corresponded to the neuroimaging abnormalities. Histology revealed diffuse histiocytic infiltration of the parenchyma. Griscelli syn- drome type 2 should be a diagnostic consideration in a child with silvery hair, neurological deterioration and enhancing multifocal white matter signal intensity changes

Griscelli syndrome type 2: A silvery hair syndrome with hemophagocytosis

Griscelli syndrome is a very rare autosomal recessive disorder with only about 60 cases reported in the literature. It is characterized by reduced pigmentation of the skin, silvery discoloration of the hair and immunodeficiency. Patients can have an accelerated hemophagocytic phase. The accelerated phase commonly occurs following an infection and has a high risk of mortality. Griscelli syndrome has to be distinguished from Chediak-Higashi syndrome and Elejalde disease, which can also present with silvery hair. In this case report, we discuss the child with silvery hair who presented with hemophagocytic lymphohistiocytosis following varicella infection and was diagnosed to have Griscelli syndrome.

A case of silvery hair syndrome: Griscelli syndrome

Chediak-Higashi syndrome, Griscelli syndrome (GS) and Elejalde disease are rare autosomal recessive disorders known as silvery hair syndromes. Here, we describe a case of a 7-year-old girl with bronze skin and silvery hair, diagnosed as GS. Three genetic types of GS are known. Pigmentary dilution is common to all three and is the only finding in Griscelli Type 3. Type 1 is associated with neurological problems and Type 2 with immunodeficiency.

Elejalde syndrome (ES)

Silvery hair and severe dysfunction of the central nervous system (Neuroectodermal melanolysosomal disease or Elejalde Syndrome) characterize this rare autosomal recessive syndrome. The main clinical features include silver-leaden hair, bronze skin after sun exposure, and neurologic involvement. Large granules of melanin unevenly distributed in the hair shaft are observed. Abnormal melanocytes and melanosomes and abnormal inclusion bodies in fibroblasts may be present. We report a 10-year-old girl with silver-leaden (silvery) hair, bronze skin color on sun-exposed areas, generalized hypopigmentation of covered body parts, and congenital seizures. The child was the elder of two children born of a consanguineous marriage. The younger sibling, a female neonate, had the same clinical presentation.

Chediak-Higashi Syndrome: A Case Series from Karnataka, India.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease, characterized by partial oculocutaneous albinism, frequent pyogenic infections, and the presence of abnormal large granules in leukocytes and other granulecontaining cells. The abnormal granules are readily seen in blood and marrow granulocytes. Other clinical features include silvery hair, photophobia, nystagmus and hepatosplenomegaly. However, the presence of abnormal giant intracytoplasmic granules in neutrophils and their precursors are diagnostic of CHS. Here, we present a series of five cases, out of which four presented in the accelerated phase. In all the five cases, the giant granules were noted predominantly in the cytoplasm of lymphocytes, which is a rare occurrence compared to those present in the granulocytes.

Chediak-higashi syndrome: a case report of a girl without silvery hair and oculocutaneous albinism presenting with hemophagocytic lymphohistiocytosis.

Chediak-higashi syndrome: a case report of a girl without silvery hair and oculocutaneous albinism presenting with hemophagocytic lymphohistiocytosis.

The GTPase-deficient Rab27A(Q78L) Mutant Inhibits Melanosome Transport in Melanocytes through Trapping of Rab27A Effector Protein Slac2-a/Melanophilin in Their Cytosol: DEVELOPMENT OF A NOVEL MELANOSOME-TARGETING TAG

The small GTPase Rab27A is a crucial regulator of actin-based melanosome transport in melanocytes, and functionally defective Rab27A causes human Griscelli syndrome type 2, which is characterized by silvery hair. A GTPase-deficient, constitutively active Rab27A(Q78L) mutant has been shown to act as an inhibitor of melanosome transport and to induce perinuclear aggregation of melanosomes, but the molecular mechanism by which Rab27A(Q78L) inhibits melanosome transport remained to be determined. In this study, we attempted to identify the primary cause of the perinuclear melanosome aggregation induced by Rab27A(Q78L). The results showed that Rab27A(Q78L) is unable to localize on mature melanosomes and that its inhibitory activity on melanosome transport is completely dependent on its binding to the Rab27A effector Slac2-a/melanophilin. When we forcibly expressed Rab27A(Q78L) on mature melanosomes by using a novel melanosome-targeting tag that we developed in this study and named the MST tag, the MST-Rab27A(Q78L) fusion protein behaved in the same manner as wild-type Rab27A. It localized on mature melanosomes without inducing melanosome aggregation and restored normal peripheral melanosome distribution in Rab27A-deficient cells. These findings indicate that the GTPase activity of Rab27A is required for its melanosome localization but is not required for melanosome transport.