Oral manifestations and craniofacial characteristics of hutchinson-gilford progeria syndrome: a case report

Introduction: Hutchinson-Guilford progeria syndrome (HGPS) is a rare genetic disease with a characteristic phenotype of premature aging in young children caused by a mutation in the LMNA gene and consequent accumulation of progerinin the cell. Aim: Describe oral manifestations of Hutchinson-Guilford progeria syndrome. Case Report: This is a case report of a six-year-old female patient with Hutchinson-Guilford Progeria syndrome. The physical examination revealed skin atrophy, lipodystrophy, hair rarefaction, prominent blood vessels of the scalp, craniofacial disproportion, perioral cyanosis and enlarged knee joints. The intraoral exam revealed limited mouth opening, mixed dentition with normal tooth anatomy and anteroinferior crowding. The eruption sequence and chronology were abnormal. The treatment plan included professional prophylaxis, the topical application of fluoride as well as both oral hygiene and dietary counselling. Monitoring the development of dentition and an early and timely dental intervention contributed to the maintenance of child's oral health. Conclusion: Early clinical and educational interventions can help patients with HGPS maintain adequate oral health status and improve their quality of life.

Introdução: A Progéria ou Síndrome de Hutchinson-Guilford (HGPS) é uma doença genética rara com um fenótipo característico de envelhecimento precoce em crianças pequenas, causado por uma mutação no gene LMNA e conseqüente acúmulo de progerina na célula. Objetivo: Descrever as manifestações orais da Síndrome de Hutchinson-Guilford. Relato do Caso: Este é um relato de caso de uma paciente de seis anos com Síndrome de Hutchinson-Guilford. O exame físico revelou atrofia da pele, lipodistrofia, rarefação dos cabelos, vasos sangüíneos proeminentes no couro cabeludo, desproporção craniofacial, cianose perioral e aumento das articulações dos joelhos. O exame intraoral revelou abertura bucal limitada, dentição mista com anatomia dentária normal e apinhamento ântero-inferior. A sequência e a cronologia de erupção estavam alteradas. O plano de tratamento incluiu profilaxia profissional, aplicação tópica de flúor, bem como orientação de higiene bucal e aconselhamento dietético. O acompanhamento do desenvolvimento da dentição e a intervenção odontológica precoce e oportuna colaboraram com a manutenção da saúde bucal da criança. Conclusão: Intervenções clínicas e educacionais precoces podem ajudar os pacientes com HGPS a manter um estado de saúde bucal adequado e melhorar sua qualidade de vida.

Analysis on six cases of Hutchinson-Gilford progeria syndrome / 中华内分泌代谢杂志

Objective@#To summarize the clinical characteristics of 6 children with Hutchinson-Gilford progeria syndrome, and to analyze the pathogenic genes carried by some patients.@*Methods@#The clinical data of 6 patients were summarized. The pathogenic genes of 4 families were analyzed. Genomic DNA was extracted from 3ml of the subject′s blood with EDTA anticoagulation. The first-generation sequencing technology was used to analyze the sequence of Lamin A/C(LMNA) gene and to identify the pathogenic mutation sites by comparing with normal sequencing results.@*Results@#All the children had typical clinical manifestations of the disease which has been previously reported in the literature, such as severe growth retardation, special skin manifestations, and distinctive craniofacial manifestations.Gene sequencing results revealed that 2 patients carried classical heterozygous mutation of LMNA c. 1824C>T(p.G608G). The other two patients carried atypical mutations of LMNA IVS8-4 C>A and c. 1968+ 2T>C, among which the mutation of IVS8-4 C>A has not been reported.@*Conclusions@#In Chinese children, both classical and non-classical mutations in LMNA gene lead to the occurrence of premature aging. It is easy to make a diagnosis based on clinical manifestations. Finding of the pathogenic gene may further confirm the diagnosis.

Research progress on lamin and Hutchinson-Gilford progeria syndrome / 中华老年医学杂志

Many studies have shown that abnormal expression and modification of lamin are closely related to aging.Hutchinson-Gilford progeria syndrome(HGPS)is a rare and severe premature aging disease caused by mutations in the gene encoding nuclear envelope proteins of A-type lamins (LMNA).The pathogenesis of HGPS is similar to the aging process of normal individuals,thus research on HGPS will be helpful for understanding the mechanisms of senescence and developing antiaging drugs.This paper reviews recent advances in lamin and the pathogenesis and treatment of HGPS,in order to provide a reference for further basic and clinical research on HGPS.

Chemical screen identifies a geroprotective role of quercetin in premature aging

Aging increases the risk of various diseases. The main goal of aging research is to find therapies that attenuate aging and alleviate aging-related diseases. In this study, we screened a natural product library for geroprotective compounds using Werner syndrome (WS) human mesenchymal stem cells (hMSCs), a premature aging model that we recently established. Ten candidate compounds were identified and quercetin was investigated in detail due to its leading effects. Mechanistic studies revealed that quercetin alleviated senescence via the enhancement of cell proliferation and restoration of heterochromatin architecture in WS hMSCs. RNA-sequencing analysis revealed the transcriptional commonalities and differences in the geroprotective effects by quercetin and Vitamin C. Besides WS hMSCs, quercetin also attenuated cellular senescence in Hutchinson-Gilford progeria syndrome (HGPS) and physiological-aging hMSCs. Taken together, our study identifies quercetin as a geroprotective agent against accelerated and natural aging in hMSCs, providing a potential therapeutic intervention for treating age-associated disorders.

A utilidade da microscopia confocal nas lesões de lentigo maligno / The utility of confocal microscopy in lentigo maligna lesions

O diagnóstico das lesões pigmentadas da face é considerado desafiador uma vez que lesões benignas e malignas podem compartilhar características clínicas e dermatoscópicas semelhantes, principalmente em lesões iniciais, sendo muitas vezes difícil de identificar as lesões de lentigo maligno da face. Assim, a microscopia confocal de reflectância pode se tornar uma ferramenta útil no diagnóstico dos lentigos malignos bem como para o seu planejamento cirúrgico.

The diagnosis of pigmented facial lesions is considered challenging since benign and malignant lesions might have similar clinical and dermoscopic features ­ especially in the early stages of the lesion ­ entailing that it is often difficult to identify lentigo maligna lesions in the face. In this way, confocal reflectance microscopy has the potential to become a useful tool both in the diagnosis and surgical planning of lentigo maligna.

Lentigo maligna and lentigo maligna melanoma: a clinicopathologic analysis of twenty-four cases / 中华病理学杂志

Objective@#To study the clinicopathologic features, differential diagnosis and prognosis of lentigo maligna (LM) and lentigo maligna melanoma (LMM).@*Methods@#Histopathologic evaluation and immunohistochemical study by HRP multimer method were carried out in 24 cases of LM and LMM from 2012 to 2017 at Fudan University Shanghai Cancer Center. The clinical information and follow-up data were analyzed.@*Results@#Of total 24 cases, there were 7 cases of LM and 17 cases of LMM; 10 males and 14 females. The age of patients ranged from 32 to 88 years (mean 67 years). The male-to-female ratio was 1.0∶1.4. Tumors were all located on head and face. Clinically, all patients presented with mottled light brown or sepia macule located on head and face for a long time, and some of them followed by nodules or ulceration within the lesion. The diameter of lesions ranged from 0.5 to 3.0 cm. Microscopically, LM and in-situ component of LMM were all characterized by a predominantly junctional proliferation of atypical melanocytes with marked pleomorphism, frequently extending down the walls of hair follicles and sweat ducts. Multinucleate cells were frequently present. The invasive components of LMM mainly consisted of atypical melanocytic spindle cells (13 cases, 76.5%), and the mean Breslow thickness was 1.2 mm (0.1-2.7 mm). The lesions of LM/LMM were generally associated with severe actinic damage, scattered infiltration of lymphocytes and melanophages. Statistically, the number of cases whose diameter of lesion ≥0.6 cm, mitotic rates ≥4/mm2 and nests of melanocytes within epidermis in group of LMM were significantly more than those in group of LM. Immunohistochemically, atypical melanocytes in LM and LMM were generally positive for S-100, HMB45, PNL2, Melan A and SOX-10. Follow-up was available in all cases, ranging from 1 to 64 months. Only one out of 23 patients with wide surgical excision had local recurrence, and the remaining 22 patients were all alive with no evidence of disease. One LM patient who was merely treated with biopsy was alive with disease progression after 20 months follow-up.@*Conclusions@#LM/LMM is a special subtype of melanoma predominantly located on the sun-exposed skin of elderly people. Recognition of its specific histologic features can help distinguish with sun-damaged diseases and other subtypes of melanoma. The prognosis of LM/LMM patients treated with surgical excision is considered relatively favorable. However, long term follow-up should be recommended in patients with LM/LMM because of high recurrence rates indicated by previous studies.

Signos dentales de la sífilis congénita / Dental signs of congenital syphilis

La sífilis congénita es causada por una bacteria en forma de espiroqueta denominada Treponema pallidum; se transmite de la madre infectadaaal feto. Esta enfermedad causa distintas alteraciones sistémicas, dependiendoen qué fase de la sífilis se infecta el producto. El incremento de casos a nivel mundial hace necesario el estudio de su epidemiología y que se implementen programas de salud que atiendan a la población embarazada, con seguimiento por medio del control prenatal. Se estima que 1.5 por ciento de las mujeres embarazadas a nivel mundial la padecen. Las alteraciones dentales tienen su etiología en la infl amación provocada por la espiroqueta al momento de la amelogénesis; los signos dentales característicos de la sífi lis congénita son los incisivos de Hutchinson, molares de mora y, en menor medida, los caninos de Fournier. El propósito de este trabajo es hacer una revisión de la literatura, enfatizando en las características clínicas de la enfermedad que nos permitan realizar el diagnóstico de la sífilis congénita.

Congenital syphilis is caused by a spirochete bacterium called Treponema pallidum; it is transmitted from the infected mother to the fetus. This disease causes diff erent systemic alterations, dependingon which phase of syphilis the product is infected. The increase incases worldwide makes it necessary to study its epidemiology andto implement health programs that serve the pregnant population, with follow-up through prenatal control. It is estimated that 1.5% of pregnant women world wide suff er from it. Dental alterations have theiretiology in the infl ammation caused by the spirochete at the momentof amelogenesis; the characteristic dental signs of congenital syphilisare Hutchinson incisors, blackberry molars, and, to a lesser extent, Fournier’s canines. The purpose of this paper is to review the literature, emphasizing the clinical characteristics of the disease that may allowus to diagnose congenital syphilis.

Synchronous conjunctival melanoma and lentigo maligna melanoma

Abstract: Lentigo maligna has an extensive and neoplastic character. It typically progresses slowly and may eventually develop into an invasive melanoma, which is called lentigo maligna melanoma. Ocular melanoma is the second most common type of melanoma. The uvea is the most common site of origin of ocular melanomas, while conjunctival melanoma accounts for about 1-5% of cases. In this article, we describe a rare case of synchronic conjunctival melanoma and lentigo maligna on the face.

Lentigo maligno na face: um desafio na conduta / Lentigo maligna on the face: a challenging conduct

Resumo O lentigo maligno é um melanoma in situ, de crescimento radial e lento, que acomete áreas fotoexpostas principalmente em idosos. Quando acomete a pálpebra, devido à proximidade a um órgão nobre, a conduta é controversa, porém a cirurgia é o método mais usado, com margens que variam de acordo com a referência utilizada. Terapias conservadoras são descritas, como o imiquimode 5% e a radioterapia. O presente relato tem como objetivo demonstrar a escassez de estudos sobre a margem cirúrgica e citar opções de tratamentos não cirúrgicos para o lentigo maligno da face.

Abstract Lentigo maligna is a melanoma in situ, of slow radial growth, which affects sun-exposed areas, especially in the elderly. When it affects the eyelid, due to the proximity to a noble organ, the conduct is controversial, but surgery is the method most commonly used, with with margins varying according to the reference used. Conservative treatments are described, such as imiquimod 5% and radiotherapy. This report aims to demonstrate the lack of studies on the surgical margin, and to name nonsurgical treatment options for lentigo maligna of the face.

Hutchinson-Gilford progeria syndrome in two brothers and literature review / 临床儿科杂志

Objective To analysis the clinical features, diagnosis and treatment of Hutchinson-Gilford progeria syndrome (HGPS). Methods The clinical data and gene testing results of HGPS in two brothers in the same family were retrospectively analyzed. The related literatures were reviewed. Results The proband was 15 years old, and his younger brother was 6 years old. Both of them presented premature appearance at 4 years old and 1 year-old respectively. Both of them suffered from underweight, short stature, reduced subcutaneous fat, bird face (prominent eyes, facial skin, scalp veins exposure, hook and prominent nose, mandibular stenosis). In addition, their trunk and limbs skin was relaxation, and they had ankylosis,and shrill voice etc.In both of them,the compound heterozygous mutation of NBAS gene(c.4081C>T,c.5741C>T)were found by full sequence exon sequencing, which were inherited from their father and mother respectively. The literature review suggested that NBAS gene mutation was associated with the diseases with main phenotype of short stature and optic atrophy.Conclusions It is reported two cases of HGPS caused by NBAS gene mutation.It is rare that two brothers have HGPS.

Clinical Features and Risk Factors of Herpes Zoster Ophthalmicus

PURPOSE: To evaluate the clinical characteristics and risk factors of severe manifestation of herpes zoster ophthalmicus. METHODS: We conducted a retrospective analysis using medical records from 106 patients diagnosed with herpes zoster ophthalmicus from January 2012 to June 2015. Patients were classified according to the type and frequency of ophthalmologic manifestations. Patients with conjunctivitis, punctate keratitis, and pseudodendritic keratitis were classified into the mild group, whereas patients with deep stromal keratitis, endothelitis, scleritis, glaucoma, and extraocular muscle paralysis were classified into the severe group. The age, sex, severity, location of skin lesions, delayed time to treatment, the presence of Hutchinson's sign, and associated systemic diseases were compared between the groups. In addition, we investigated changes in vision, intraocular pressure, treatment duration, recurrence and the prevalence of postherpetic neuralgia. RESULTS: The incidence of conjunctivitis (47.2%), punctate keratitis (42.5%), pseudodendritic keratitis (12.2%), deep stromal keratitis (12.2%), endothelitis (15.1%), scleritis (18.9%), glaucoma (14.2%), and extraocular muscle (EOM) paralysis (4.7%) were observed in these patients. The group with mild disease included 70 cases with conjunctivitis, punctate keratitis and pseudodendritic keratitis. The severe group included 36 cases with deep stromal keratitis, endothelitis, scleritis, glaucoma and EOM palsy. Disease most often occurred in the distribution of the first branch of the trigeminal nerve, with no differences in the age or sex of patients in both groups. Severe manifestations were more common when a greater extent of the skin was involved, when Hutchinson's sign was present, or when treatment was significantly delayed. There were no significant differences between the two groups in recurrence or the presence of postherpetic neuralgia. CONCLUSION: Long-term treatment for herpes zoster opthalmicus is more likely to be required if severe manifestation of disease exists, such as widespread skin involvement, Hutchinson's sign, or a delay to the initiation of antiviral treatment. More active observation and treatment are required in such cases.

Cutaneous Melanoma in Asians / 전남의대학술지

Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. It can occur in any melanocyte-containing anatomic site. Four main cutaneous melanoma subtypes are recognized: lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma (ALM), and nodular melanoma. Generally, excessive exposure to ultraviolet (UV) radiation increases the risk of melanoma. The exception is ALM, which is the most common melanoma subtype in Asians and is not associated with UV radiation. ALM presents as dark brownish to black, irregular maculopatches, nodules, or ulcers on the palms, soles, and nails. The lesions may be misdiagnosed as more benign lesions, such as warts, ulcers, hematomas, foreign bodies, or fungal infections, especially in amelanotic acral melanomas where black pigments are absent. The aim of this brief review is to improve understanding and the rate of early detection thereby reducing mortality, especially regarding cutaneous melanoma in Asians.

Cutaneous Melanoma in Asians / 전남의대학술지

Malignant melanoma is a rare disease in Asians but potentially the most aggressive form of skin cancer worldwide. It can occur in any melanocyte-containing anatomic site. Four main cutaneous melanoma subtypes are recognized: lentigo maligna melanoma, superficial spreading melanoma, acral lentiginous melanoma (ALM), and nodular melanoma. Generally, excessive exposure to ultraviolet (UV) radiation increases the risk of melanoma. The exception is ALM, which is the most common melanoma subtype in Asians and is not associated with UV radiation. ALM presents as dark brownish to black, irregular maculopatches, nodules, or ulcers on the palms, soles, and nails. The lesions may be misdiagnosed as more benign lesions, such as warts, ulcers, hematomas, foreign bodies, or fungal infections, especially in amelanotic acral melanomas where black pigments are absent. The aim of this brief review is to improve understanding and the rate of early detection thereby reducing mortality, especially regarding cutaneous melanoma in Asians.

Contoured technique for lentigo maligna

The surgical approach to lentigo maligna is a challenge to dermatologists, given the difficulty of clinical delimitation of borders. We report here a case of a 69-year-old female patient presenting with brownish macules on her face, since 10 years ago, with histopathological diagnosis of lentigo maligna. The surgical management employed was excision of visible borders with the contoured technique and immediate submission of these borders for histopathological analysis before complete excision of the tumor. This technique is a variant of staged excision, with lower rates of recurrence and acceptable aesthetic results.

An Overview of Hutchinson Gilford Progeria Syndrome (HGPS).

Hutchinson Gilford Progeria Syndrome (HGPS) is a rare genetic disorder. The disorder is characterized by premature aging, generally leading to death. The purpose of this article is to review Hutchinson Gilford Progeria Syndrome and its characteristics. There are many symptoms from various organs such dermatology characteristics, facial features, and musculoskeletal disorders. The syndrome is characterized by specific radiological and histological findings. The diagnosis is based on the identification of common clinical features and the detection of mutation of specific gene. There are some types of treatment may facilitate or delay some of the signs and symptoms.A multidisciplinary team should intervene in order to increase the quality of life and survival of Hutchinson-Gilford progeria syndrome.

Melanoma lentiginoso acral com sinal de Hutchinson: relato de caso / Acral lentiginous melanoma with Hutchinson's sign: case report

Contexto: O sinal de Hutchinson é o derrame de pigmento melânico periungueal no melanoma ungueal e indica a propagação superficial do tumor. Descrição do caso: Descrevemos o caso de uma paciente negra, de 54 anos, com lesão ungueal há dois anos. Relatou trauma importante nessa região há 40 anos e, posteriormente, há 27 anos. Ao exame dermatológico, foi detectada a presença de unha distrófica com melanoníquia extensa e derrame pigmentar na região subungueal distal. O diagnóstico histológico revelou melanoma lentiginoso acral. Em relação ao diagnóstico do melanoma do aparelho ungueal, Levit e cols. propuseram um sistema para sua detecção, priorizando algumas características, as quais foram agrupadas segundo as letras do alfabeto A, B, C, D, E, F: A (age) - idade, B (nailband) - faixa, C (change) - mudança, D (digit involved) - local envolvido, E (extension) - sinal de Hutchinson e F (family) - história familiar. No caso relatado, cinco letras estavam presentes, o que sugeriu o diagnóstico de melanoma, visto que a precisão diagnóstica é maior quanto maior a somatória de letras. Conclusões: O melanoma lentiginoso acral é um tipo raro de neoplasia maligna, muitas vezes não diagnosticado. O diagnóstico precoce é de grande importância para o tratamento, e, consequentemente, para a sobrevida do paciente.

Progeria: A rare genetic premature ageing disorder.

Progeria is characterized by clinical features that mimic premature ageing. Although the mutation responsible for this syndrome has been deciphered, the mechanism of its action remains elusive. Progeria research has gained momentum particularly in the last two decades because of the possibility of revealing evidences about the ageing process in normal and other pathophysiological conditions. Various experimental models, both in vivo and in vitro, have been developed in an effort to understand the cellular and molecular basis of a number of clinically heterogeneous rare genetic disorders that come under the umbrella of progeroid syndromes (PSs). As per the latest clinical trial reports, Lonafarnib, a farnesyltranferase inhibitor, is a potent ‘drug of hope’ for Hutchinson-Gilford progeria syndrome (HGPS) and has been successful in facilitating weight gain and improving cardiovascular and skeletal pathologies in progeroid children. This can be considered as the dawn of a new era in progeria research and thus, an apt time to review the research developments in this area highlighting the molecular aspects, experimental models, promising drugs in trial and their implications to gain a better understanding of PSs.

Dermatoscopia das lesões pigmentadas na face: um desafio diagnóstico / Dermoscopy of pigmented lesions of the face: a diagnostic challenge

A dermatoscopia do lentigo maligno na face tem parâmetros confiáveis e bem testados para sua diagnose. Algumas lesões benignas, como as queratoses actínicas pigmentadas, apresentam, contudo, aspectos dermatoscópicos comuns aos lentigos malignos, dificultando a correta diagnose. Isso muitas vezes leva a excisões desnecessárias de lesões benignas. Este artigo discute esses parâmetros morfológicos no escopo de analisar os pontos em comum entre lentigo maligno e queratose actínica pigmentada com a dermatoscopia, assim como coteja os aspectos já descritos para a diagnose das queratoses actínicas pigmentadas.

Dermoscopy of lentigo maligna on the face has reliable and well-tested parameters for its diagnosis. However, some benign lesions such as pigmented actinic keratoses have dermoscopic aspects that are common in malignant lentigo, making the correct diagnosis difficult. This fact often leads to unnecessary excisions of benign lesions. The present article discusses these morphological parameters in light of the dermoscopic analysis of the commonalities between lentigo maligna and pigmented actinic keratosis, also touching upon the aspects already described for the diagnosis of pigmented actinic keratoses.

Comparison of Herpes Zoster Ophthalmicus in Patients 60 Years Older Versus Younger than 60 Years

PURPOSE: To analyze and compare the clinical characteristics of patients with herpes zoster ophthalmicus (HZO) by age groups on the basis of the age of 60. METHODS: Medical records of patients with HZO who visited Chonbuk National University Hospital from February 1, 2002 to February 28, 2011 were reviewed. The patients with follow-up of three months or more were divided into two groups: patients under 60 and patients with 60 years old and over. The clinical characteristics between two groups were examined through the analysis of their medical records. RESULTS: Among a total of 63 patients, 29 patients (46%) were under 60 years old, and 34 patients (54%) were 60 years old and over. Incidence of HZO highest in the sixties. The sex and intrusion of each group showed no difference. Younger patients had a higher incidence of pseudodendrite by HZO (86.2% vs. 58.8%, p = 0.014) compared with older patients who showed a higher incidence of post herpetic neuralgia (13.8% vs. 35.3%, p = 0.046). As patients showed Hutchinson's sign, they often had more ocular complications such as pseudodendrite (100% vs. 64.7%, p < 0.05), uveitis (41.7% vs. 7.8%, p = 0.04), and conjunctivitis (100% vs. 90.2%, p = 0.02). CONCLUSIONS: Herpes zoster ophthalmicus shows different clinical characteristics according to patients' age and requires appropriate treatment. Especially elderly patients showing Hutchinson's sign should be treated early and aggressively enough.