RESUMO
BACKGROUND: Mutations in the cytokine receptor-like factor 1 (CRLF1) gene are responsible for Crisponi/Cold-induced Sweat Syndrome, an extremely rare autosomal-recessive multisystem disorder. The protein encoded is a soluble cytokine receptor, involved in the ciliary neurotrophic factor receptor (CNTFR) pathway. The ciliary neurotrophic factor (CNTF) promotes corneal wound healing and patients with Crisponi/CISS1 syndrome suffer from recurrent keratitis. The aim of the study was to report and discuss the corneal alterations in Crisponi/CISS1 rare disease. MATERIALS AND METHODS: We evaluated the cornea of both eyes in four Crisponi/CISS1 patients to provide a detailed description of slit-lamp biomicroscopy findings. Corneal sensitivity, tears functionality and blinking video recording at rest were also assessed in all patients. Two patients were also evaluated with in vivo confocal microscopy, completed with a needle electromyography of their orbicularis muscles. RESULTS: None of the patients presented a tears dysfunction and video recording documented a prolonged lid excursion in all patients. Slit lamp examination revealed a chronic epithelial impairment in all cases. Needle electromyography of the orbicularis oculi showed a dystonic pattern. The confocal microscopy confirmed the biomicroscopic observed lesions and documented unusual findings of the corneal nerve plexus. CONCLUSIONS: This is the first report of microscopic cornea alterations explored with confocal imaging in Crisponi/CISS1 patients. The observed corneal findings suggest a possible direct correlation to the CNTFR pathway defect and the blinking imbalance could exacerbate the compromised epithelial wound healing. Topical administrations of lubricating eye drops are strongly recommended in these patients.
Assuntos
Doenças da Córnea/diagnóstico , Epitélio Corneano/patologia , Deformidades Congênitas da Mão/diagnóstico , Hiperidrose/diagnóstico , Trismo/congênito , Adolescente , Adulto , Criança , Córnea/inervação , Morte Súbita , Eletromiografia , Fácies , Feminino , Deformidades Congênitas da Mão/genética , Humanos , Hiperidrose/genética , Masculino , Microscopia Confocal , Músculos Oculomotores/fisiologia , Lâmpada de Fenda , Doenças do Nervo Trigêmeo/diagnóstico , Trismo/diagnóstico , Trismo/genética , Adulto JovemRESUMO
INTRODUCTION: Cold-induced sweating syndrome type 1 (CISS1), is a rare, severe, autosomal recessive disease. It is characterized by morphological alterations and profuse sweating when ambient temperature is <22 °C. Although some individuals with CISS1 have decreased pain perception, no study has been conducted to evaluate thermal and pain sensations in these patients. The aim of this study was to assess the function of the nociceptive Aδ-fibers and warmth C-fibers by using CO2 laser-evoked potentials (LEPs) in patients affected by CISS1. METHODS: Four patients were studied. Laser pulses were applied to the skin of the right hand and the perioral region at painful intensity to record Aδ-LEPs, and at non-painful intensity to obtain C-LEPs. Fifteen healthy subjects were studied for control purposes. RESULTS: No significant difference in latencies or amplitudes of either Aδ- or C-LEPs was found between the 2 groups. CONCLUSION: Cutaneous nociceptive and warmth pathway functions are normal in CISS1. Muscle Nerve 54: 100-103, 2016.
Assuntos
Deformidades Congênitas da Mão/fisiopatologia , Hiperidrose/fisiopatologia , Potenciais Evocados por Laser/fisiologia , Nociceptividade/fisiologia , Temperatura , Trismo/congênito , Adolescente , Adulto , Morte Súbita , Fácies , Feminino , Humanos , Masculino , Tempo de Reação/fisiologia , Pele/inervação , Trismo/fisiopatologiaRESUMO
OBJECTIVE: This work investigated the molecular cause responsible for a late-onset parkinsonism-dystonia phenotype in three Italian siblings, and clinically characterize this condition. METHODS: Extensive neurophysiological and neuroradiological exams were performed on the three sibs. Most frequent late-onset metabolic diseases were ruled out through laboratory and biochemical analyses. A whole exome sequencing (WES) approach was used to identify the molecular cause underlying this condition. RESULTS AND CONCLUSIONS: Peculiar neurologic phenotype was characterized by dystonia-parkinsonism, cognitive impairment, gait ataxia and apraxia, pyramidal signs. WES analysis allowed the identification of a compound heterozygosity for two nucleotide substitutions (c.1340G>A, p.R447H; c.790C>T, p.Q264X) affecting the TPP1 gene in the three affected siblings. Biochemical analyses demonstrated abrogated TPP1 catalytic activity in primary skin fibroblasts, but revealed residual activity in leukocytes. Our findings document that late infantile neuronal ceroid lipofuscinosis (CLN2), which is caused by TPP1 gene mutations, should be considered in the differential diagnosis of autosomal recessive dystonia-parkinsonism syndromes. The availability of enzyme replacement therapy and other therapeutic approaches for ceroid lipofuscinoses emphasizes the value of reaching an early diagnosis in patients with atypical and milder presentation of these disorders.
Assuntos
Aminopeptidases/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Mutação/genética , Lipofuscinoses Ceroides Neuronais , Serina Proteases/genética , Biologia Computacional , Eletroencefalografia , Potenciais Evocados/fisiologia , Feminino , Humanos , Itália , Masculino , Lipofuscinoses Ceroides Neuronais/genética , Lipofuscinoses Ceroides Neuronais/metabolismo , Lipofuscinoses Ceroides Neuronais/patologia , Irmãos , Pele/metabolismo , Pele/patologia , Pele/ultraestrutura , Tripeptidil-Peptidase 1 , Adulto JovemRESUMO
INTRODUCTION: Costello syndrome (CS) is a multisystemic disorder characterized by postnatal reduced growth, facial dysmorphism, cardiac defects, cognitive impairment, skin and musculo-skeletal anomalies, and predisposition to certain cancers. CS is caused by activating germline mutations in the HRAS proto-oncogene. Similar to what is observed in other RASopathies, CS causative HRAS mutations promote enhanced signal flow through the RAF-MEK-ERK and PI3K-AKT signaling cascades. While decreased bone mineralization has been documented in other RASopathies, such as neurofibromatosis type 1 and Noonan syndrome, systematic studies investigating bone mineral density (BMD) are lacking in CS. MATERIALS AND METHODS: Dual-energy X-ray absorptiometry (DXA) was utilized to assess BMD and body composition (fat and fat-free mass) in a cohort of subjects with molecularly confirmed diagnosis of CS (n = 9) and age-matched control individuals (n = 29). Using general linear regression, subtotal body (total body less head), lumbar, femoral neck and femur BMD parameters were compared considering age, sex, body mass index (BMI) and Tanner stage. Blood and urine biomarkers of bone metabolism were also assessed. RESULTS: All individuals with CS showed significantly lower mean values of subtotal, lumbar and femoral neck BMD compared to the control group (p ≤ 0.01). Similarly, mean total body mass and fat-free mass parameters were lower among the CS patients than in controls (p < 0.01). Low 25-OH vitamin D concentration was documented in all individuals with CS, with values below the reference range in two patients. No significant correlation between vitamin D levels and BMD parameters was observed. DISCUSSION: CS belongs to a family of developmental disorders, the RASopathies, that share skeletal defects as a common feature. The present data provide evidence that, similar to what is recently seen in NF1 and NS, bone homeostasis is impaired in CS. The significant decrease in BMD and low levels of vitamin D documented in the present cohort, along with the risk for pathologic fractures reported in adult individuals with CS, testifies the requirement for a preventive treatment to alleviate evolutive complications resulting from dysregulated bone metabolism.
Assuntos
25-Hidroxivitamina D 2/sangue , Absorciometria de Fóton/métodos , Composição Corporal/fisiologia , Densidade Óssea/fisiologia , Síndrome de Costello/fisiopatologia , Adolescente , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Feminino , Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Proto-Oncogene Mas , Adulto JovemRESUMO
A 4-year-old girl was hospitalized for psychomotor delay, low vision, and horizontal nystagmus. She was found to have bilateral chorioretinal atrophic scars and 2 large occipital porencephalic cavities. High plasma ornithine levels led to the presumed diagnosis of gyrate atrophy of the choroid and retina. After 6 months of arginine-restricted diet and high-dose pyridoxine (300 mg/d), there was no change of plasma ornithine level or ocular findings. To our knowledge, this is the first report showing an association of porencephaly with gyrate atrophy of the choroid and retina.
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Encefalopatias/etiologia , Doenças da Coroide/etiologia , Atrofia Girata/etiologia , Degeneração Retiniana/etiologia , Atrofia , Encefalopatias/patologia , Pré-Escolar , Doenças da Coroide/patologia , Feminino , Atrofia Girata/complicações , Atrofia Girata/patologia , Atrofia Girata/terapia , Humanos , Imageamento por Ressonância Magnética , Degeneração Retiniana/patologiaRESUMO
We report a 7-year-old boy who unexpectedly developed a multi-drug resistant epilepsy with negative neuroimaging results, followed by the insidious appearance of linear localized scleroderma involving the right leg. When the boy was 16 and severely affected by epileptic encephalopathy, we have evaluated this case for the first time: his localized scleroderma had reached the right buttock and positive anti-nuclear antibody was the only positive laboratory test. Methotrexate administered for 12 months was ineffective in improving both the organization of his electroencephalographic pattern and seizure control, though seemed to stabilize the progression of linear scleroderma. This report suggests that neurological abnormality and extracranial scleroderma might represent two own distinct processes in a same patient.
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Epilepsia/complicações , Adolescente , Antirreumáticos/uso terapêutico , Criança , Resistência a Medicamentos , Eletroencefalografia , Epilepsia/tratamento farmacológico , Humanos , Masculino , Metotrexato/uso terapêutico , Esclerodermia Localizada/complicações , Esclerodermia Localizada/tratamento farmacológicoRESUMO
We report a case of large pericardial effusion which has been managed with pericardiocentesis as the main presentation feature of a dramatic clinical picture, only retrospectively framed as referred to macrophage activation syndrome in a child with juvenile idiopathic arthritis at its onset. The risk of developing this rare and severe complication should be recognized in various pathological settings of childhood, above all in children displaying systemic signs of juvenile idiopathic arthritis.