Silvery Gray Hair Research Articles

Griscelli syndrome: a diagnostic challenge of a rare disease: a case report

Introduction: Griscelli syndrome (GS) is a rare autosomal recessive genetic disorder that primarily manifests as hair and skin hypopigmentation, with three types differentiated by their specific genetic defects as well as by their clinical features. Clinically, GS type 1 is characterized by early neurological alterations, while GS type 2 is characterized by immunodeficiency and could present with neurological symptoms, and type 3 is characterized by a chromosomal anomaly without a specific clinical profile besides hypopigmentation. This article details the challenges faced in the diagnosis of a patient with GS who presents with neurological symptoms followed by immunological deficits. Case presentation: A 7-month-old female presented with complaints of developmental delay following an otitis media infection. Upon examination, she exhibited signs of psychomotor developmental regression and had pale bronze skin and silvery-gray hair, as well as hepatosplenomegaly. The examination of her hair shaft revealed a pattern consistent with GS. During her hospitalization, the patient developed an intermittent fever and signs of hemophagocytic lymphohistiocytosis (HLH). She subsequently developed recurrent seizures treated with phenytoin and Aciclovir. Shortly she succumbed to respiratory distress syndrome and multisystem failure. Discussion: The presence of HLH confirms the type of GS. However, in some cases, the HLH criteria could not be fulfilled, presenting a diagnostic challenge. Conclusion: The genetic examination is the only way to differentiate GS type 1 from type 2. However, when it is not available, the presence of specific symptoms and features may assist in the classification. Furthermore, treatments should be administered when GS type 2 is suspected since they have the potential to improve life quality through treating HLH, delaying and altering the neurological symptoms.

Cutaneous presentation in chediak – Higashi syndrome – A rare case report

A One and half year-old female child born out of 2consanguineous marriage came with multiple hypopigmented patches over the face, trunk and lower limbs. There was history of recurrent upper respiratory tract infections. On examination she had silvery grey hair, hypopigmented patches and mild hepatomegaly. Ophthalmological examination revealed oculocutaneous albinism. Skin biopsy showed coarse clumps of melanin pigment in the epidermis. Hair mount examination revealed melanin granules in cortex and medulla. Routine blood investigations were within normal limits. Peripheral smear examination showed giant granules in neutrophils and lymphocytes.

Clinical and Biological Characteristics of a Griscelli Syndrome Type 2: About a Case Report

Introduction: Griscelli Syndrome (GS) is a rare autosomal recessive genetic disorder, characterized by a partial albinism that can be associated with early-onset severe psychomotor retardation, and normal immune status (type 1), or associated with an immune deficiency (type 2). GS type 2 results from mutations in the RAB27A gene, leading to immune deficiency. GS type 2 has a grave prognosis because of a rapidly fatal macrophage activated syndrome. Case Report: A 3-month-old infant having a family history of first-degree consanguinity in the parents and history of silvery gray hair in two uncles, Admitted to our department for management of a prolonged fever and an anemic syndrome. Hair on the scalp, eyebrows, and eyelashes were silvery gray and had a metallic sheen. The lymphocyte sub typing showed a severe combined immune deficiency. Histological examination of the hair showed enlarged, hyper pigmented basal melanocytes with sparse pigmentation of adjacent keratinocytes in favor of a Griscelli syndrome. The evolution was marked by clinical worsening, respiratory distress. On the biological level, a macrophage activation syndrome was retained in front of a hyperferritinemia, a hypertriglyceridemia and hepatic cytolysis. The patient received broad-spectrum antibiotic therapy, antivirals and antifungals, corticosteroid boluses 3 days in a row and an immunoglobulin infusion. Unfortunately, the patient died of septic shock. Conclusion: Type 2 GS is a rare genetic disease with a poor prognosis, which must be diagnosed early to allow better support. The only curative treatment is bone marrow transplantation.

Unusual Presentation of Griscelli Syndrome type II, Case Report.

Abstract: Griscelli syndrome (GS) is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, Elejalde), RAB27A (GS2) or MLPH (GS3) genes. All three subtypes of this disease present by pigmentary dilution of the hair and skin with silvery-grey hair. Whereas this is the only feature in GS3 phenotype, GS1 patients also have primary neurological impairment and GS2 patients show severe immunological deficiencies leading to recurrent infections and hemophagocytic syndrome. We report here the case of GS2 in a10-year-old boy, with immunodeficiency and recurrent infections with hemophagositic lymphohistocytosis but without pigmentary changes.

Griscelli Syndrome Type 3 in Three Non-Identical Siblings

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.

Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth.

Rab27a/b are known to play an important role in the transport of melanosomes, with their knockout causing silvery gray hair. However, the relationship between Rab27a/b and hair growth is not well known. To evaluate the role of Rab27a/b in hair cycle, we investigated the expression of Rab27a/b during hair cycling and human outer root sheath (hORS) cells. The expression of Rab27a in ORS cells was mainly detected at the anagen, whereas expression of Rab27b in ORS, and epidermal cells was strongly expressed at the telogen. Additionally, Rab27a/b were expressed in the Golgi of hORS cells. To evaluate the role of Rab27a/b in hair growth, telogen-to-anagen transition animal and vibrissae hair follicles (HFs) organ culture models were assayed using Rab27a/b siRNAs. The knockdown of Rab27a or Rab27b suppressed or promoted hair growth, respectively. These results were also confirmed in human dermal papilla cells (hDPCs) and hORS cells, showing the opposite mitogenic effects. Moreover, Rab27b knockdown increased the expression levels of various growth factors in the hDPCs and hORS cells. Overall, the opposite temporal expression patterns during hair cycling and roles for hair growth of Rab27a/b suggested that Rab27a/b might regulate the hair cycle. Therefore, our study may provide a novel solution for the development of hair loss treatment by regulating Rab27a/b levels.

Griscelli Syndrome Type 2: A Rare Case With Apparently Normal Skin and Hair Pigmentation

t- Griscelli syndrome (GS) is a rare autosomal recessive disease that affects hair, skin, and immune system. Here, we describe an 8.5-month-old infant with multiple admissions due to fever, petechial purpura, and several recurrent vomiting episodes with a presumptive diagnosis of recurrent sepsis. He was born from parents with consanguineous marriage. The initial examinations revealed huge splenomegaly and hepatomegaly without any source of infection. Laboratory tests revealed a hemophagocytic lymphohistiocytosis (HLH) like a picture with a high blood level of ferritin in all episodes, but the bone marrow test result was normal. Although he had normal hair and skin pigmentation on physical examination, the accumulation of melanosomes was found in his hair shafts on microscopic investigations. Eventually, a genetic test revealed a mutation in the RAB27A gene, which confirmed GS-II diagnosis. Our case is the first case of GS-II from Iran without any apparent clinical features of GS, such as hypopigmented skin and silvery-gray hair. Therefore, a genetic test, together with the microscopic examination of hair and skin, is necessary for the diagnosis and confirmation of GS-II. Since GS-II is an autosomal recessive disorder and consanguineous marriages are popular in Iran, premarital genetic counseling is recommended for this region.

RAB27A mutation in a patient with griscelli syndrome type 2, successfully cured by hematopoietic stem cell transplantation: Sustained remission

Griscelli syndrome (GS) is a rare autosomal recessive disorder. It features with clinical constellation of skin hypopigmentation, silvery-gray hair, associated with neurological involvement (type I), or defective cell-mediated immunity with hemophagocytosis (type II) that leads to recurrent infection, and patients succumb to death in early childhood or isolated “quiet” GS (type III). To our knowledge, more than sixty patients have been reported mainly from the Mediterranean region with the first reported Saudi cases, reported by Harfi et al. in 1992. The outcome of GS is guarded if not treated early due to recurrent fulminant infections, disease recurrence, and the impending severity of central nervous system disease. Hematopoietic stem cell transplantation (HSCT) is the single current therapeutic treatment for GS II. HSCT, therefore, should be performed as early as possible to prevent potential complications. The reported patient had sustained remission and normal hematopoietic function after allogeneic bone marrow transplant from a human leukocyte antigen-identical sibling donor. GS II syndrome should be considered in any child with hypopigmented skin, silvery-gray hair, and primary immunodeficiency. Early recognition and early HSCT intervention are associated with favorable outcome.

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.

Silvery gray hair syndromes: An insight into diagnosis

Context: Silvery gray hair syndromes consist of three conditions, Chediak–Higashi syndrome (CHS), Griscelli syndrome (GS), and Elejalde syndrome (ES), which are rare autosomal recessive diseases presenting in childhood. They have similar skin and hair changes but differ with respect to the other clinical findings. Aim: This retrospective study was taken up to identify the spectrum of silvery gray hair syndromes diagnosed over a period of 10 years (2006-2015) in a super specialty pediatric institute and also to identify characteristic clinical and diagnostic findings. Methods: A total of 17 children diagnosed to have silvery gray hair syndrome over a period of 10 years (2006-2015) at Indira Gandhi Institute of Child Health Hospital, Bengaluru and were studied retrospectively. Complete blood counts, peripheral smear study, and microscopic examination findings of the hair were analyzed. Radiological findings were also considered. Results: The most common syndrome in the study was GS Type II (10 cases) followed by CHS (5 cases), with one case each of GS Type III and ES. Conclusion: This study emphasizes the importance of silvery gray hair as a clue to diagnose these rare genetic disorders with proper clinical examination and simple diagnostic procedures.

Griscelli syndrome subtype 2 with hemophagocytic lympho-histiocytosis: A case report and review of literature

Griscelli syndrome (GS) is a rare autosomal recessive disorder resulting in pigmentary dilution of the skin and hair with variable phenotypes depending upon subtypes. Mutations in 3 distinct genes MYO5A, RAB27A, MLPH are responsible for 3 subtypes (GS1, GS2, and GS3) of GS respectively. GS subtype 2 commonly develops hemophagocytic lymphohistiocytosis (HLH) and recurrent infections due to immunodeficiency. We hereby report a 20 month old male child presenting with silvery gray hair, hypomelanosis and features of hemophagocytosis. The diagnosis of a type 2 GS was made in response to a set of clinical features: hypopigmentation of skin and the silvered reflection of the hair, absence of psychomotor retardation, the occurrence of an accelerated phase (hemophagocytosis) and, above all, a pathognomonic appearance by microscopic examination of a hair. The absence of giant granules in the nucleated cells made it possible to eliminate Chediak-Higashi syndrome, which shares a close clinical spectrum with GS. This case promotes awareness about this rare case of GS as a high indicator of suspicion about this potentially fatal condition and aids in prompt diagnosis and foresees complications. Early bone marrow transplant is the only curative treatment for GS-2.

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.

Griscelli syndrome type 2 – A case report and clinical approach to silver blonde hair

Griscelli syndrome type 2 is a rare autosomal recessive disease caused by mutations in the RAB27A gene. It is characterized by pigmentary dilution of the skin and hair causing silvery gray hair, hemophagocytic lymphohistiocytosis and characteristic light microscopy findings in scalp hair shaft seen as large irregular clumps of pigment as opposed to the evenly distributed pigment along the hair shaft without any clumps. We describe a boy with classic features of Griscelli syndrome type 2 from Pakistan in whom a homozygous mutation in the RAB27A gene was identified that showed a single base substitution (c.598C>T) predicted to cause premature protein termination (p.Arg200∗). We also present a clinical approach to silver blonde hair differentiating between the Griscelli syndrome types 1, 2 and 3, Chediak Hegashi Syndrome and Elejalde Syndrome.

Griscelli Syndrome Type 3: Two New Cases and Review of the Literature

A 3-year-old Arab boy with a history of hypoplastic left heart syndrome was referred to the pediatric dermatology clinic at Sheba Medical Center for evaluation of hypomelanosis, manifested by fair skin pigmentation and silvery-grey hair, eyebrows, and eyelashes. The child had one older brother with similar hypopigmentation and another older brother who had died of congenital heart disease. The child had no history of neurologic deficits or immunodeficiency and no additional findings on clinical evaluation.

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

Teaching Neuro Images : Griscelli syndrome and CNS lymphohistiocytosis

A 3-year-old boy developed viral illness followed by fever, altered sensorium, focal seizures, and neuroregression. Examination showed silvery-gray hair (figure 1A), bilateral papilledema, spastic quadriparesis, brisk muscle-stretch reflexes, extensor plantars, hepatosplenomegaly, and normally pigmented skin, iris, and retina. Hair microscopy confirmed Griscelli syndrome (GS) (figure 1, B-D). MRI brain was suggestive (figure 2, A-D). CSF showed 20 degenerated leukocytes. He died of an intercurrent illness 2 months later.

Griscelli Syndrome Type 2 With Hemophagocytic Lymphohistocytosis a Rare and Lethal Disorder

A two and half years old male child was admitted with silvery grey hair, recurrent chest infection, ear discharge, hepatosplenomegaly, pancytopenia and hemophagocytosis in bone marrow. Light microscopy of hair shaft showed large unevenly distributed melanin pigment. Skin biopsy showed large coarse aggregates of melanin and the basal layer of epidermis showed reactivity with Masson ’ s fontana stain. Griscelli syndrome type 2 was made as diagnosis which was confirmed by mutation study which showed nonsense mutation of Exon 6 of RAB 27A gene. The child was in accelerated phase and succumbed to death. doi: http://dx.doi.org/10.4021/ijcp100w

Silvery-Gray Hair in a Newborn

Silvery-Gray Hair in a Newborn

Griscelli syndrome types 1 and 3: analysis of four new cases and long-term evaluation of previously diagnosed patients

Griscelli syndrome (GS) is a rare autosomal recessive disorder characterized by partial albinism. Three different types are caused by defects in three different genes. Patients with GS type 1 have primary central nervous system dysfunction, type 2 patients commonly develop hemophagocytic lymphohistiocytosis, and type 3 patients have only partial albinism. While hematopoietic stem cell transplantation is life saving 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, only 2 patients with type 3 and about 20 GS type 1 patients, including the patients described as Elejalde syndrome, have been reported. The neurological deficits in Elejalde syndrome were reported as severe neurodevelopmental delay, seizures, hypotonia, and ophthalmological problems including nystagmus, diplopia, and retinal problems. However, none of these patients' clinical progresses were reported. We described here our two new type 1 and two type 3 patients along with the progresses of our previously diagnosed patients with GS types 1 and 3. Our previous patient with GS type I is alive at age 21 without any other problems except severe mental and motor retardation, patients with type 3 are healthy at ages 21 and 24 years having only pigmentary dilution; silvery gray hair, eye brows, and eyelashes. Since prognosis, treatment options, and genetic counseling markedly differ among different types, molecular characterization has utmost importance in GS.

Silvery grey hair: Clue to diagnose immunodeficiency

Silvery hair is a common presentation of rare group of autosomal recessive disorders called Silvery hair syndromes including Griscelli syndrome (GS), Chediak-Higashi syndrome, and Elejalde syndrome. GS is characterized by a silvery grey sheen to hair, large clumped melanosomes in hair shaft, partial albinism, and variable cellular immunodeficiency. We report two cases of GS with classical clinical features and confirmatory findings by microscopic skin and hair examination.