A rare LMNA missense mutation causing a severe phenotype of mandibuloacral dysplasia type A: a case report.

OBJECTIVE: To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal defects, associated with a rare homozygous LMNA missense mutation (c.1579C>T). CASE DESCRIPTION: A 6-year-old girl was evaluated during hospitalization exhibiting the following dysmorphic signs: subtotal alopecia, dysmorphic facies with prominent eyes, marked micrognathia and retrognathia, small beaked nose, teeth crowding and thin lips, generalized lipodystrophy, narrow and sloping shoulders, generalized joint stiffness and bone reabsorption in the terminal phalanges. In dermatological examination, atrophic skin, loss of cutaneous elasticity, hyperkeratosis, dermal calcinosis, and hyperpigmented and hypochromic patches were observed. Radiology exams performed showed bilateral absence of the mandibular condyles, clavicle resorption with local amorphous bone mass confluence with the scapulae, shoulder joints with subluxation and severe bone dysplasia, hip dysplasia, osteopenia and subcutaneous calcifications. COMMENTS: MADA is a rare autosomal recessive disease caused by mutations in LMNA gene. It is characterized by craniofacial deformities, skeletal anomalies, skin alterations, lipodystrophy in certain regions of the body and premature ageing. Typical MADA is caused by the p.R527H mutation in the LMNA gene. However, molecular analysis performed from oral epithelial cells obtained from the patient showed the rare mutation c.1579C>T, p. R527C in the exon 9 of LMNA. This is the sixth family identified with this mutation described in the literature.

A rare LMNA missense mutation causing a severe phenotype of mandibuloacral dysplasia type A: a case report / Uma rara mutação missense no gene LMNA causando um fenótipo grave de displasia mandibuloacral tipo A: relato de caso

ABSTRACT Objective: To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal defects, associated with a rare homozygous LMNA missense mutation (c.1579C>T). Case description: A 6-year-old girl was evaluated during hospitalization exhibiting the following dysmorphic signs: subtotal alopecia, dysmorphic facies with prominent eyes, marked micrognathia and retrognathia, small beaked nose, teeth crowding and thin lips, generalized lipodystrophy, narrow and sloping shoulders, generalized joint stiffness and bone reabsorption in the terminal phalanges. In dermatological examination, atrophic skin, loss of cutaneous elasticity, hyperkeratosis, dermal calcinosis, and hyperpigmented and hypochromic patches were observed. Radiology exams performed showed bilateral absence of the mandibular condyles, clavicle resorption with local amorphous bone mass confluence with the scapulae, shoulder joints with subluxation and severe bone dysplasia, hip dysplasia, osteopenia and subcutaneous calcifications. Comments: MADA is a rare autosomal recessive disease caused by mutations in LMNA gene. It is characterized by craniofacial deformities, skeletal anomalies, skin alterations, lipodystrophy in certain regions of the body and premature ageing. Typical MADA is caused by the p.R527H mutation in the LMNA gene. However, molecular analysis performed from oral epithelial cells obtained from the patient showed the rare mutation c.1579C>T, p. R527C in the exon 9 of LMNA. This is the sixth family identified with this mutation described in the literature.

RESUMO Objetivo: Relatar o caso de uma jovem que apresentava um fenótipo grave de displasia mandibuloacral tipo A (MADA) caracterizado por alterações osteolíticas proeminentes e defeitos ectodérmicos, associados a uma rara mutação homozigótica missense no gene LMNA (c.1579C>T). Descrição do caso: Uma menina de seis anos foi avaliada durante hospitalização apresentando os seguintes sinais dismórficos: alopecia subtotal, fácies dismórfica com olhos proeminentes, micrognatia e retrognatia acentuada, nariz pequeno e adunco, dentes apinhados e lábios finos, lipodistrofia generalizada, ombros estreitos e inclinados, rigidez articular e reabsorção óssea nas falanges terminais. Ao exame dermatológico, observou-se pele atrófica, perda da elasticidade cutânea, hiperceratose, calcinose dérmica e manchas hiperpigmentadas e hipocrômicas. Exames radiológicos realizados mostraram ausência de côndilos mandibulares bilaterais, reabsorção da clavícula com massa óssea amorfa local confluindo com as escápulas, articulações do ombro com subluxação e displasia óssea severa, com displasia coxofemoral, osteopenia e calcificações subcutâneas. Comentários: MADA é uma doença autossômica recessiva rara causada por mutações no gene LMNA. Caracteriza-se por deformidades craniofaciais, anomalias esqueléticas, alterações cutâneas, lipodistrofia em determinadas regiões do corpo e envelhecimento precoce. MADA típica é causada pela mutação p.R527H no gene LMNA. No entanto, a análise molecular realizada com células epiteliais orais obtidas da paciente mostrou a mutação rara c.1579C>T, p. R527C no exon 9 do gene LMNA. Esta é a sexta família identificada com essa mutação descrita na literatura.

Increased number of Herpes Zoster cases in Brazil related to the COVID-19 pandemic.

Coronavirus 2019 (COVID-19), caused by the pathogen SARS-CoV-2, was declared a pandemic in March 2020. Recently, studies have discussed reports of patients infected with COVID-19 associated with vesicular manifestations of Herpes Zoster. The objective of this study was to compare the data from the Unified Health System (SUS) on the number of diagnoses of Herpes Zoster from March to August from 2017 to 2019, with the same period in 2020, in the five Brazilian regions (North, Northeast, Southeast, South, and Midwest). The data were extracted from the public database (DATASUS) of Brazil's Ministry of Health. The data showed an increase in the number of Herpes Zoster diagnoses over the years and the negative impact from the COVID-19 disease, revealing an average increase corresponding to an extra 10.7 cases per million inhabitants during the pandemic in all Brazilian Regions. Therefore, although the association between HZ and COVID-19 is not well established, we observed in this study an increase in HZ cases during the COVID -19 pandemic, which suggests a correlation between these diseases.

Report of two unrelated families with Jalili syndrome and a novel nonsense heterozygous mutation in CNNM4 gene.

Jalili syndrome (JS) is an autosomal recessive disease characterized by a combination of cone-rode retinal dytrophy (CRD) and amelogenesis imperfect (AI). Mutations in cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) gene cause JS. Here we described 2 families (3 members) affected by JS. In the first family, JS was caused by the homozygous p.Leu324Pro (c.971T > C) missense mutation and the affected patient developed both CRD and AI. In the second family, a specific combination of a compound heterozygous mutation was found - the p.Leu324Pro (c.971T > C) missense transition and the novel p.Tyr581* (c.1743C > G) nonsense mutation. The proband showed CRD and AI, but her father just developed eye alterations. Together, these findings suggest that the p.Leu324Pro mutation in homozygosis induces a complete phenotype with both CRD and AI, but in heterozygosis and in composition with the novel p.Tyr581* nonsense mutation in CNNM4 promotes variable clinical expressivity, particularly with lack of dental phenotypes. These different phenotypes could be explained by deletions affecting the proband's homologous allele, epistasia or interactions with environmental factors leading to residual activity of protein.

Primary Sjögren syndrome in a 2-year-old patient: role of the dentist in diagnosis and dental management with a 6-year follow-up.

BACKGROUND. Primary Sjögren syndrome is a rare autoimmune disease, especially in children, mainly affecting girls (77%), and usually diagnosed around 10 years of age. Diagnosis during childhood is difficult, especially because of the diversity of the clinical presentation and difficulty obtaining reliable history data, accounting for a higher frequency of underdiagnosed cases. Differential conditions should be considered, especially the ones that promote xerostomia, such as diabetes, ectodermal dysplasia, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, sarcoidosis, lymphoma, HIV and HTLV infection. Conditions associated with parotid enlargement should also be excluded, including juvenile recurrent parotitis (JRP), sialadenosis, sarcoidosis, lymphoma, infectious parotitis caused by streptococcal and staphylococcal infections, viral infections (paramyxovirus, Epstein-Barr virus, cytomegalovirus, and parvovirus), and diffuse infiltrative lymphocytosis syndrome (associated with HIV infection), and rare congenital conditions, such as polycystic parotid disease. CASE REPORT. A paediatric female patient was referred to our clinic for dental treatment complaining about dry mouth, oral discomfort, and dysphagia. The patient presented five of the required criteria to establish the diagnosis of pSS, including ocular symptoms, oral symptoms, evidence of keratoconjunctivitis sicca, focal sialadenitis confirmed by minor salivary gland biopsy, and evidence of major salivary gland involvement. Our patient did not have positive SS-A and SS-B autoantibodies. According to the literature, about 29% of individuals with pSS can present seronegativity for SS-A (anti-Ro) antibodies and about 33% can present seronegativity for SS-B (anti-La) antibodies. CONCLUSION. To the best of our knowledge, this is the youngest patient reported in the scientific English literature with pSS. Primary Sjögren syndrome has a wide clinical and immunologic spectrum and may progress with increased morbidity. Clinicians must be aware of the development of pSS in such an early age and exclude all possible differential findings to provide early diagnosis and treatment.