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Hair Shaft Examination: a Practical Tool to Diagnose Griscelli Syndrome

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Hair Shaft Examination: a Practical Tool to Diagnose Griscelli Syndrome Case Report Hair Shaft Examination: A Practical Tool to Diagnose Griscelli Syndrome Trinidad Montero-Vilchez 1 , Alexandra Remon-Love 2, Jesús Tercedor-Sánchez 1,* and Salvador Arias-Santiago 1 1 Department of Dermatology, Hospital Universitario Virgen de las Nieves, 18012 Granada, Spain; [email protected] (T.M.-V.); [email protected] (S.A.-S.) 2 Department of Pathology, Hospital Universitario Virgen de las Nieves, 18012 Granada, Spain; [email protected] * Correspondence: [email protected] Abstract: Griscelli syndrome (GS) is a rare disease that is characterized by silvery hair and fair skin. It is included in congenital grey hair syndromes, a rare group of autosomal recessive disorders characterized by silvery grey hair and severe multisystem disorders, such as immune system impair- ment, defects in immunological function, ocular and skeletal alterations, and nervous system defects. Herein, we report a rare case of GS type 1 and highlight the importance of a dermatological and hair examination to make an early diagnosis of these life-threatening diseases. Keywords: Griscelli syndrome; hair shaft; silvery Citation: Montero-Vilchez, T.; 1. Introduction Remon-Love, A.; Tercedor-Sánchez, J.; Griscelli syndrome (GS) is a rare skin disease characterized by a silvery hair and Arias-Santiago, S. Hair Shaft cutaneous hypopigmentation [1]. Three types of GS have been described. GS type 1 is char- Examination: A Practical Tool to acterized by hypomelanosis and primary neurological deficit [2]. GS type 2 manifests as Diagnose Griscelli Syndrome. hypomelanosis and immune deterioration [3]. GS type 3 only shows skin manifestations [4]. Dermatopathology 2021, 8, 49–53. This syndrome starts between infancy and childhood. Besides shiny hair and fair skin, https://doi.org/10.3390/ patients with GS type 1 have delayed motor development, intellectual disability, and hypo- dermatopathology8010010 tonia [2]. Patients with GS type 2 tend to have an associated cytotoxic lymphocyte defect, resulting in a hemophagocytic syndrome of uncontrolled macrophage and T-lymphocyte Academic Editor: Gürkan Kaya activation. Activated lymphocytic T cells and macrophages infiltrate lymph nodes and other organs (including the brain), leading to a hemophagocytosis phenomenon [3]. Received: 4 February 2021 GS type 1 is caused by mutations in the MYO5A gene located on chromosome 15q21, Accepted: 7 March 2021 GS type 2 is caused by mutations in the RAB27A (15q21.3) gene, and GS type 3 is caused by Published: 9 March 2021 mutations in the MLPH (2q37.3) gene [1,5,6]. GS type 1 inheritance is autosomal recessive. This means that if both parents were heterozygous carriers for the pathogenic mutation, the Publisher’s Note: MDPI stays neutral theoretical risk for the offspring would be 25% homozygous affected, 50% asymptomatic with regard to jurisdictional claims in heterozygous carrier, and 25% non-affected non-carrier [2]. published maps and institutional affil- iations. 2. Case Report A 10-year-old Spanish girl presented to our dermatologic clinic with discoloration of the scalp and eyebrow since birth. She was born out of consanguineous marriage and had a twin sister with similar phenotype. A 13-year-old brother was healthy. The patient’s clinical Copyright: © 2021 by the authors. history revealed that she also suffered from developmental delay and epilepsy with tonic- Licensee MDPI, Basel, Switzerland. clonic seizures. Moreover, she had severe neuromuscular scoliosis, with perpendicular This article is an open access article obliquity of sapropelic origin. She also suffered from gastro-oesophageal reflux and was distributed under the terms and conditions of the Creative Commons being studied by an endocrinologist for early puberty. Attribution (CC BY) license (https:// The physical examination showed facial hypopigmentation, greyish eyebrows, and creativecommons.org/licenses/by/ grey hair tufts (Figure1). Laboratory studies showed normal results. Hair shaft exami- 4.0/). nation under light microscopy showed giant uneven melanin granules in the medullar Dermatopathology 2021, 8, 49–53. https://doi.org/10.3390/dermatopathology8010010 https://www.mdpi.com/journal/dermatopathology Dermatopathology 2021, 8 50 Dermatopathology 2021, 8 50 Dermatopathology 2021, 8 50 The physical examination showed facial hypopigmentation, greyish eyebrows, and grey Thehair physicaltufts (Figure examination 1). Laboratory showed studies facial showed hypopigmentation, normal results. greyish Hair eyebrows,shaft examina- and tiongrey under hair tufts light (Figure microscopy 1). Laboratory showed giant studies un evenshowed melanin normal granules results. in Hair the shaftmedullar examina- zone zone(Figurestion under (Figures 2 and light2 3),and microscopy a 3typical), a typical characteristic showed characteristic giant obse unrvedeven observed in melanin Griscelli in Griscelli granules syndrome syndrome in (GS).the medullar So, (GS). regarding So,zone regardingclinical(Figures manifestation 2 clinical and 3), manifestationa typical and microscopycharacteristic and microscopy features observed, the features, in patient Griscelli the was syndro patient diagnome wassed (GS). diagnosed with So, GS regarding type with 1. GSFollowingclinical type manifestation 1. Followingethics approval and ethics microscopy and approval informant andfeatures informantconsent,, the patient DNA consent, was DNAextracteddiagno wassed fromextractedwith peripheralGS type from 1. peripheralbloodFollowing samples. bloodethics The samples. approval diagnosed The and diagnosed of informant GS type of 1consent, GSwas type then DNA 1 confirmed, was was then extracted confirmed, as the patient from as the peripheral was patient a ho- was a homozygous carrier of the pathogenic variant c.5152C>T (p.Gln1718*) in the MYO5A mozygousblood samples. carrier The of diagnosed the pathogenic of GS variant type 1 wasc.5152C>T then confirmed, (p.Gln1718*) as the in thepatient MYO5A was agene ho- gene NM_000259.3. NM_000259.3.mozygous carrier of the pathogenic variant c.5152C>T (p.Gln1718*) in the MYO5A gene NM_000259.3. FigureFigure 1. 1.Silvery Silvery greygrey scalp scalp hair. hair. Figure 1. Silvery grey scalp hair. Figure 2. Microscopic examination of a hair shaft. FigureFigure 2. 2.Microscopic Microscopic examination examination of of a a hair hair shaft. shaft. Dermatopathology 2021, 8 51 Dermatopathology 2021, 8 51 FigureFigure 3. 3.Hair Hair shaft shaft showing showing large large irregular irregular melanin melanin granules. granules. 3.3. Discussion Discussion GSGS is is included included inin congenitalcongenital grey hair syndromes, syndromes, a arare rare group group of of autosomal autosomal recessive reces- sivedisorders disorders characterized characterized by silvery by silvery grey grey hair, hair, defects defects in immunological in immunological function, function, and andnerv- nervousous system system defects. defects. Besides Besides GS, Chediak–Higash GS, Chediak–Higashii syndrome syndrome (CHS), Elej (CHS),alde syndrome Elejalde syn- (ES), dromeand oculocerebral (ES), and oculocerebral hypopigmentation hypopigmentation syndrome Cr syndromeoss type (OHS) Cross are type also (OHS) included are also[6]. It includedwas previously [6]. It was mentioned previously that mentioned GS type 1 that is characterized GS type 1 is characterized by hypomelanosis by hypomelanosis and primary andneurological primary neurologicaldeficit [2]. GS deficit type 2 [manifests2]. GS type as 2hypomelanosis manifests as hypomelanosis and immune deterioration and immune [3]. deteriorationGS type 3 only [3]. shows GS type skin 3 onlymanifestations shows skin [4]. manifestations CHS is characterized [4]. CHS by is characterizedsevere cell immu- by severenodeficiency cell immunodeficiency and oculocutaneous and albinism oculocutaneous with silver albinism hair [7]. with ES manifests silver hair with [7]. neurologic ES mani- festsdefects with and neurologic ocular signs defects such and as nystagmus, ocular signs di suchplopia, as nystagmus, or congenital diplopia, amaurosis or congenital [8]. OHS is amaurosischaracterized [8]. OHSby neurological is characterized signs, by growth neurological deficiency, signs, intellectual growth deficiency, disability, intellectual and ocular disability,signs such and as ocularmicrophthalmia signs such or as ectropium microphthalmia [9]. or ectropium [9]. Clinically,Clinically, it it is is difficult difficult to to distinguish distinguish these these disorders, disorders, as as their their clinical clinical features features may may overlap.overlap. Nevertheless, Nevertheless, the the clinical clinical history, history, physical physical examination, examination, and and hair hair shaft shaft examination examination couldcould provide provide a a rapid rapid clinical clinical suspicion suspicion of of this this severe severe disease. disease. Moreover, Moreover, GS GS and and CHS CHS can can bebe differentiated differentiated by by hair hair microscopy microscopy [10 [10].]. Large Large irregular irregular melanin melanin granules granules are are observed observed in allin typesall types ofGS, of GS, while while small small melanin melanin granules granules homogeneously homogeneously distributed distributed are are shown shown in in CHS [11]. CHS [11]. Dermatopathology in GS is characterized by enlarged hyperpigmented basal Dermatopathology in GS is characterized by enlarged hyperpigmented basal mela- melanocytes with sparsely pigmented adjacent keratinocytes. Large pigment clumps nocytes
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