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1.
Nat Genet ; 51(5): 793-803, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31043756

RESUMO

Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study (GWAS) including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P < 1 × 10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (P < 5 × 10-8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis, 30 loci were genome-wide significant, including 20 newly identified loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene sets, including regulation of insulin secretion and endocannabinoid signaling. Bipolar I disorder is strongly genetically correlated with schizophrenia, driven by psychosis, whereas bipolar II disorder is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential biological mechanisms for bipolar disorder.


Assuntos
Transtorno Bipolar/genética , Loci Gênicos , Transtorno Bipolar/classificação , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Transtornos Psicóticos/genética , Esquizofrenia/genética , Biologia de Sistemas
2.
Nat Genet ; 51(3): 431-444, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30804558

RESUMO

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.


Assuntos
Transtorno do Espectro Autista/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Dinamarca , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Herança Multifatorial/genética , Fenótipo , Fatores de Risco
3.
Nat Genet ; 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30478444

RESUMO

Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.

4.
J Adolesc Health ; 63(6): 759-765, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30279103

RESUMO

PURPOSE: Despite the psychosocial deficits associated with gynecomastia, surgical treatment of adolescent gynecomastia remains controversial. This longitudinal cohort study measures changes in health-related quality of life following surgical treatment of gynecomastia in adolescents. METHODS: The following surveys were administered to adolescents with gynecomastia and male controls, aged 12-21 years: Short-Form 36v2 (SF-36), Rosenberg Self-Esteem Scale (RSES), and Eating-Attitudes Test-26. Subjects completed surveys at baseline and postoperatively/at follow-up at 6 months, 1 year, 3 years, and 5 years. RESULTS: From 2008 to 2017, 44 patients undergoing surgical treatment of gynecomastia and 64 unaffected male controls participated in our study. At baseline, gynecomastia patients scored significantly worse than controls on the RSES and in five SF-36 domains: general health, vitality, social functioning, role-emotional, and mental health. Scores significantly improved postoperatively on the RSES, and in four SF-36 domains: physical functioning, role-physical, bodily pain, and social functioning. Postoperatively, gynecomastia subjects scored similarly to controls in all SF-36 domains and the RSES. Young and overweight/obese patients and those with severe gynecomastia had the greatest postoperative improvement across survey measures. CONCLUSIONS: Surgical treatment of gynecomastia significantly improves the quality of life of adolescents, with measurable improvements in physical and psychosocial functioning. Postoperatively, gynecomastia patients performed comparably to unaffected controls. Surgical treatment of gynecomastia in adolescents and young men has the potential to significantly improve quality of life, particularly in younger and overweight/obese patients and those with moderate to severe gynecomastia. Concerns regarding patient age and body mass index alone should not contraindicate surgery.

5.
Pediatrics ; 140(5)2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28986442

RESUMO

OBJECTIVES: To measure changes in health-related quality of life and breast-related symptoms after reduction mammaplasty in adolescents. METHODS: In this longitudinal cohort study, we administered the Short-Form 36v2 (SF-36), Rosenberg Self-Esteem Scale (RSES), Breast-Related Symptoms Questionnaire (BRSQ), and Eating Attitudes Test-26 to 102 adolescents with macromastia and 84 female controls, aged 12 to 21 years. Patients with macromastia completed surveys preoperatively and after reduction mammaplasty at 6 months and 1, 3, and 5 years. Controls completed baseline and follow-up surveys at the same intervals. RESULTS: Patients with macromastia demonstrated significant score improvements postoperatively from baseline on the RSES, BRSQ, and in 7 out of 8 SF-36 domains: physical functioning, role-physical, bodily pain, vitality, social functioning, role-emotional, mental health (P < .001, all). By the 6-month follow-up visit, postoperative subjects scored similarly to or more favorably than controls on the RSES, BRSQ, Eating Attitudes Test-26 , and SF-36; these benefits persisted for at least 5 years and were not significantly affected by BMI category or age. CONCLUSIONS: Reduction mammaplasty was significantly associated with improvements in health-related quality of life and breast-related symptoms of adolescent patients, with measureable improvements in physical and psychosocial well-being evident by 6 months postoperatively and still demonstrable after 5-years. These results largely do not vary by BMI category or age. Patients and providers should be aware of the potential positive impact that reduction mammaplasty can provide adolescents with symptomatic macromastia. Historic concerns regarding age and BMI category at the time of surgery should be reconsidered.


Assuntos
Mama/anormalidades , Hipertrofia/psicologia , Hipertrofia/cirurgia , Mamoplastia/psicologia , Satisfação do Paciente , Qualidade de Vida/psicologia , Autoimagem , Adolescente , Mama/cirurgia , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Mamoplastia/tendências , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
7.
Breast J ; 21(3): 254-9, 2015 May-Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25772491

RESUMO

Giant fibroadenomas (5 cm or greater) are benign breast masses that often present in adolescence and require surgical excision. Long-term outcomes, recurrence rates, and the need for additional reconstructive surgery in this population are unknown. Patients aged 11-25 years whose pathology reports indicated the presence of a giant fibroadenoma were eligible for this study. Medical records were reviewed for presentation, treatment, and outcomes. A subset of patients completed an investigator-designed long-term outcome survey to measure additional outcomes and the desire or need for subsequent reconstructive surgery. Forty-six patients with at least one giant fibroadenoma (mean size 7.4 ± 2.8 cm) were identified. Most patients underwent excision with a periaroeolar incision (n = 31), and an enucleation technique (n = 41), and four patients underwent immediate breast reconstruction. Thirty-three patients had complete medical records with a mean follow-up time of 2.2 ± 4.1 years and no complaints of asymmetry, additional breast deformities, or reconstructive surgery procedures documented. In addition, nine patients completed the investigator-designed survey with a mean follow-up time of 10.1 ± 8.7 years (range 1.5-27.0). Three of these patients reported postoperative breast asymmetry and the desire to pursue reconstructive surgery. Aesthetic outcomes of giant fibroadenoma excision may be satisfactory for many patients without immediate reconstruction, but for others, the need for reconstructive surgery may arise during development. Providers should address this potential need prior to discussing treatment options and during postoperative follow-up. Caution should be exercised before recommending immediate reconstruction.


Assuntos
Neoplasias da Mama/cirurgia , Fibroadenoma/cirurgia , Adolescente , Neoplasias da Mama/patologia , Criança , Estética , Feminino , Fibroadenoma/patologia , Seguimentos , Inquéritos Epidemiológicos , Humanos , Mamoplastia/métodos , Recidiva Local de Neoplasia , Resultado do Tratamento , Adulto Jovem
8.
J Hand Surg Am ; 40(3): 452-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25542431

RESUMO

PURPOSE: To examine the efficacy of preoperative electrocardiogram (EKG) screening for Timothy syndrome, a rare and fatal condition characterized by prolonged QT, in children referred for syndactyly release. METHODS: We reviewed the records of nonsyndromic syndactyly patients seen by a hand surgeon at our institution between 2007 and 2013. All underwent a preoperative screening EKG for Timothy syndrome. We reviewed the medical records for demographics, presentation, EKG results, and operative findings, and calculated median age at the time of EKG and surgery and frequency distributions for sex, side affected, EKG result, and clinical finding. The mean patient charge for EKG and interpretation was calculated. RESULTS: We identified 128 syndactyly patients, 72% of which were boys. Median age at the time of EKG testing and syndactyly release was 1 year. A total of 92% of patients had normal EKG results; one patient exhibited a prolonged QT. Ten patients (8%) had further cardiac evaluation because of the EKG result and were found to be normal on repeat testing. No patient met QT threshold for Timothy syndrome and all patients were cleared for surgery. The minimum patient charge for EKG testing was $183. CONCLUSIONS: To improve patient safety, some have advocated preoperative EKG testing for all children undergoing syndactyly release to rule out Timothy syndrome. Analysis of our experience failed to yield an instance of Timothy syndrome over a 7-year period. Although EKG charges were relatively low, costs resulting from additional testing, cardiology consultation, and provider and parent time should be considered. Our study does not support routine EKG testing for children referred for syndactyly release, and we have abandoned this practice. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.


Assuntos
Transtorno Autístico/diagnóstico , Eletrocardiografia/métodos , Síndrome do QT Longo/diagnóstico , Sindactilia/cirurgia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Síndrome do QT Longo/complicações , Síndrome do QT Longo/genética , Masculino , Segurança do Paciente , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Sindactilia/complicações , Sindactilia/diagnóstico , Sindactilia/genética , Resultado do Tratamento
9.
Plast Reconstr Surg ; 134(6): 1116-23, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25415081

RESUMO

BACKGROUND: This study measures the impact of adolescent breast asymmetry compared with macromastia and female controls. METHODS: The following surveys were given to patients with breast asymmetry, macromastia, and controls aged 12 to 21 years: Short Form Health Survey, Version 2 (Short Form-36), the Rosenberg Self-Esteem Scale, and the Eating Attitudes Test. Demographics were compared, and linear regression models, adjusted for body mass index category and age, were fit to determine the effect of case status on survey score. RESULTS: Fifty-nine adolescents with asymmetry, 142 controls, and 160 macromastia patients participated. After controlling for differences in body mass index category, asymmetry patients scored lower on psychological Short Form-36 domains and the Rosenberg Self-Esteem Scale than controls (p < 0.05), but did not differ in physical health. When compared with macromastia adolescents, asymmetry patients scored significantly better on Short Form-36 physical health domains (p < 0.05), but had similar decrements in emotional functioning, mental health, self-esteem, and eating behaviors/attitudes, after accounting for differences in age. Age and asymmetry type and severity had no effect on survey scores, independent of body mass index category (p > 0.05). Asymmetry patients had a higher mean body mass index percentile than controls (83.36 versus 73.52) but did not differ from that of macromastia patients (83.39). CONCLUSIONS: Breast asymmetry may negatively impact the psychological quality of life of adolescents similar to macromastia. Breast asymmetry is not just a cosmetic issue. Providers should be aware of the psychological impairments associated with asymmetry and provide proper support.


Assuntos
Imagem Corporal , Mama/anormalidades , Saúde Mental , Autoimagem , Adolescente , Estudos de Casos e Controles , Criança , Comportamento Alimentar , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertrofia/psicologia , Modelos Lineares , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
10.
Plast Reconstr Surg ; 133(5): 654e-661e, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24776567

RESUMO

BACKGROUND: Pfeiffer syndrome is characterized by craniosynostosis and a variety of associated upper and lower extremity anomalies. The authors reviewed presentation and treatment of upper extremity anomalies in a series of genotyped patients with Pfeiffer syndrome. METHODS: Medical records of patients with Pfeiffer syndrome seen at the authors' institution over a 16-year period were reviewed. Data on clinical presentation, genetic testing, and treatment were collected. The upper extremity anomalies were documented using plain radiographs and physical examinations by a multidisciplinary craniofacial team. RESULTS: Of 15 patients identified as having FGFR1- or FGFR2-confirmed Pfeiffer syndrome, 12 (80 percent) presented with upper extremity anomalies, most commonly broad thumbs [n = 10 (83 percent)], radial clinodactyly (thumbs) [n = 7 (58 percent)], and symphalangism [n = 7 each (58 percent)]. All patients with upper extremity anomalies had lower extremity anomalies. Six of the 12 patients (50 percent) with upper extremity findings underwent surgical correction. FGFR1 or FGFR2 genotype did not correlate with upper extremity phenotype. CONCLUSIONS: Although broad thumbs are common, patients with Pfeiffer syndrome often present with other upper extremity anomalies that may not require surgical intervention. Genetic and allelic heterogeneity may explain phenotypic variability in these upper extremity anomalies. Characterization of these limb differences should be made by pediatric hand surgeons as part of a craniofacial team. Treatment decisions should be individualized and dictated by the type and severity of clinical presentation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.


Assuntos
Acrocefalossindactilia/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Polegar/anormalidades , Acrocefalossindactilia/diagnóstico por imagem , Acrocefalossindactilia/cirurgia , Criança , Pré-Escolar , Feminino , Genótipo , Deformidades Congênitas da Mão/diagnóstico por imagem , Deformidades Congênitas da Mão/genética , Deformidades Congênitas da Mão/cirurgia , Humanos , Lactente , Masculino , Mutação , Fenótipo , Sítios de Splice de RNA , Radiografia , Estudos Retrospectivos , Sinostose/diagnóstico por imagem , Sinostose/genética , Sinostose/cirurgia , Polegar/diagnóstico por imagem , Polegar/cirurgia
11.
J Hand Surg Am ; 38(11): 2112-23, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24060511

RESUMO

PURPOSE: To characterize the presentation, treatment, and early outcomes of children with isolated congenital macrodactyly of the hand. METHODS: We performed a retrospective chart review of isolated hand macrodactyly cases treated at our institution over a 15-year period. Data on clinical presentation, procedure details, and outcomes were collected. RESULTS: A total of 21 patients, 8 boys and 13 girls, were identified. Patients had a mean of 1.8 affected digits (median, 2; range, 1-3); most (n = 12; 57%) presented with multiple affected digits. The middle finger was most commonly affected (67%). Most patients had progressive overgrowth (n = 13; 67%). Twelve patients (57%) had nerve territory-oriented macrodactyly, whereas 9 (43%) presented with lipomatous type. There were no differences between the types of macrodactyly in sex, affected side, rate of growth, digits affected, or number of procedures. Patients underwent a mean of 3.2 staged corrective operations (median, 2; range, 1-12), including soft tissue debulking (n = 19 patients; 90%), ostectomy for volume reduction or partial amputation (n = 9; 43%), closing wedge osteotomy (n = 11; 52%), epiphysiodesis (n = 7; 33%), digit transfer (n = 3; 14%), toe transfer (n = 1; 5%), and ray amputation (n = 6; 29%). Patients with progressive growth underwent more procedures than patients with static growth. No major complications were reported. CONCLUSIONS: The diagnosis of macrodactyly should be reserved for patients with isolated congenital digit overgrowth affecting all tissue types, but clinical presentation and natural history of macrodactyly can vary greatly among patients. A variety of surgical techniques exist to reconstruct rather than amputate affected digits primarily. Although reconstruction will not result in a normal digit and requires multiple operations, our observations suggest that they are well tolerated and may offer some restored function and aesthetics. More long-term outcomes and insight into the biological basis of this disorder are needed to make better-informed treatment decisions. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Assuntos
Dedos/anormalidades , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/cirurgia , Osteotomia/métodos , Criança , Feminino , Dedos/diagnóstico por imagem , Dedos/cirurgia , Deformidades Congênitas da Mão/diagnóstico por imagem , Humanos , Masculino , Radiografia , Procedimentos Cirúrgicos Reconstrutivos , Estudos Retrospectivos
12.
Plast Reconstr Surg ; 131(4): 890-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23542261

RESUMO

BACKGROUND: The purpose of this study was to determine the physical and psychosocial impact of gynecomastia and its severity on adolescents seeking treatment as compared with healthy adolescent males. METHODS: The following surveys were administered to adolescents with gynecomastia and healthy male controls, aged 12 to 21 years: Short Form-36 Version 2, the Rosenberg Self-Esteem Scale, and the Eating Attitudes Test-26. Demographic variables were compared between the two groups, and controls were administered a short chest symptoms survey. Linear regression models, unadjusted and adjusted for body mass index category, were fit to determine the effect of case status and graded severity of gynecomastia on survey score. RESULTS: Forty-seven patients with gynecomastia and 92 male control subjects participated in this study. There was no difference in mean age between the groups, although patients with gynecomastia had a significantly higher body mass index. Gynecomastia subjects had three lower Short Form-36 domain and Rosenberg Self-Esteem Scale scores independent of body mass index category as compared with controls, although there was no difference in Eating Attitudes Test-26 scores between the groups. Graded gynecomastia severity had no effect on survey scores, all independent of body mass index category. CONCLUSIONS: Gynecomastia has a significant negative impact on primarily the psychosocial well-being of affected adolescent patients, specifically in regard to social functioning, mental health, and self-esteem. Psychosocial impact was not affected by graded severity of disease. Health care providers and patients should be aware of the psychosocial impairments associated with gynecomastia and consider early treatment for adolescents suffering from this condition, regardless of severity.


Assuntos
Ginecomastia/psicologia , Adolescente , Estudos de Casos e Controles , Criança , Humanos , Masculino , Estudos Prospectivos , Inquéritos e Questionários , Adulto Jovem
13.
Am J Hum Genet ; 92(4): 621-6, 2013 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-23541344

RESUMO

Scalp-ear-nipple (SEN) syndrome is a rare, autosomal-dominant disorder characterized by cutis aplasia of the scalp; minor anomalies of the external ears, digits, and nails; and malformations of the breast. We used linkage analysis and exome sequencing of a multiplex family affected by SEN syndrome to identify potassium-channel tetramerization-domain-containing 1 (KCTD1) mutations that cause SEN syndrome. Evaluation of a total of ten families affected by SEN syndrome revealed KCTD1 missense mutations in each family tested. All of the mutations occurred in a KCTD1 region encoding a highly conserved bric-a-brac, tram track, and broad complex (BTB) domain that is required for transcriptional repressor activity. KCTD1 inhibits the transactivation of the transcription factor AP-2α (TFAP2A) via its BTB domain, and mutations in TFAP2A cause cutis aplasia in individuals with branchiooculofacial syndrome (BOFS), suggesting a potential overlap in the pathogenesis of SEN syndrome and BOFS. The identification of KCTD1 mutations in SEN syndrome reveals a role for this BTB-domain-containing transcriptional repressor during ectodermal development.


Assuntos
Anormalidades Múltiplas/etiologia , Síndrome Brânquio-Otorrenal/etiologia , Displasia Ectodérmica/etiologia , Exoma/genética , Hipospadia/etiologia , Hipotonia Muscular/etiologia , Mutação de Sentido Incorreto/genética , Proteínas Repressoras/genética , Anormalidades Múltiplas/patologia , Sequência de Aminoácidos , Síndrome Brânquio-Otorrenal/patologia , Orelha Externa/anormalidades , Orelha Externa/patologia , Displasia Ectodérmica/patologia , Feminino , Humanos , Hipospadia/patologia , Masculino , Dados de Sequência Molecular , Hipotonia Muscular/patologia , Mamilos/anormalidades , Mamilos/patologia , Linhagem , Fenótipo , Estrutura Terciária de Proteína , Couro Cabeludo/anormalidades , Couro Cabeludo/patologia , Homologia de Sequência de Aminoácidos
14.
Semin Plast Surg ; 27(1): 23-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24872735

RESUMO

Fibroadenomas are benign breast masses that can present a management challenge in adolescent populations. Most fibroadenomas may be managed conservatively without surgery, but those masses that are symptomatic or increasing in size may require surgical excision. In adolescents, the implications of surgical intervention in the breast are unclear, and there is little outcomes data. In this article, the authors discuss the presentation, diagnosis, and management of fibroadenoma in adolescents. Key considerations for physicians in treating these masses in this population are reviewed.

15.
PLoS One ; 7(7): e40423, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22848377

RESUMO

Macrodactyly is a rare family of congenital disorders characterized by the diffuse enlargement of 1 or more digits. Multiple tissue types within the affected digits are involved, but skeletal patterning and gross morphological features are preserved. Not all tissues are equally involved and there is marked heterogeneity with respect to clinical phenotype. The molecular mechanisms responsible for these growth disturbances offer unique insight into normal limb growth and development, in general. To date, no genes or loci have been implicated in the development of macrodactyly. In this study, we performed the first transcriptional profiling of macrodactyly tissue. We found that pleiotrophin (PTN) was significantly overexpressed across all our macrodactyly samples. The mitogenic functions of PTN correlate closely with the clinical characteristics of macrodactyly. PTN thus represents a promising target for further investigation into the etiology of overgrowth phenotypes.


Assuntos
Proteínas de Transporte/biossíntese , Citocinas/biossíntese , Perfilação da Expressão Gênica , Deformidades Congênitas dos Membros/metabolismo , Regulação para Cima , Feminino , Dedos/anormalidades , Dedos/patologia , Dedos/cirurgia , Humanos , Lactente , Recém-Nascido , Deformidades Congênitas dos Membros/patologia , Deformidades Congênitas dos Membros/cirurgia , Masculino
16.
Pediatrics ; 130(2): e339-46, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22802601

RESUMO

OBJECTIVE: To determine the physical and psychosocial impact of macromastia on adolescents considering reduction mammaplasty in comparison with healthy adolescents. METHODS: The following surveys were administered to adolescents with macromastia and control subjects, aged 12 to 21 years: Short-Form 36v2, Rosenberg Self-Esteem Scale, Breast-Related Symptoms Questionnaire, and Eating-Attitudes Test-26 (EAT-26). Demographic variables and self-reported breast symptoms were compared between the 2 groups. Linear regression models, unadjusted and adjusted for BMI category (normal weight, overweight, obese), were fit to determine the effect of case status on survey score. Odds ratios for the risk of disordered eating behaviors (EAT-26 score ≥ 20) in cases versus controls were also determined. RESULTS: Ninety-six subjects with macromastia and 103 control subjects participated in this study. Age was similar between groups, but subjects with macromastia had a higher BMI (P = .02). Adolescents with macromastia had lower Short-Form 36v2 domain, Rosenberg Self-Esteem Scale, and Breast-Related Symptoms Questionnaire scores and higher EAT-26 scores compared with controls. Macromastia was also associated with a higher risk of disordered eating behaviors. In almost all cases, the impact of macromastia was independent of BMI category. CONCLUSIONS: Macromastia has a substantial negative impact on health-related quality of life, self-esteem, physical symptoms, and eating behaviors in adolescents with this condition. These observations were largely independent of BMI category. Health care providers should be aware of these important negative health outcomes that are associated with macromastia and consider early evaluation for adolescents with this condition.


Assuntos
Hipertrofia/psicologia , Adolescente , Índice de Massa Corporal , Mama/anormalidades , Mama/cirurgia , Criança , Estudos Transversais , Intervenção Médica Precoce , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Hipertrofia/epidemiologia , Hipertrofia/cirurgia , Mamoplastia , Sobrepeso/epidemiologia , Sobrepeso/psicologia , Qualidade de Vida/psicologia , Fatores de Risco , Autoimagem , Estatística como Assunto , Inquéritos e Questionários , Adulto Jovem
17.
Pediatr Dermatol ; 29(4): 448-53, 2012 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22211716

RESUMO

The diagnosis of atypical Spitz tumor (AST) in a pediatric patient conveys an uncertain potential for malignancy. Although pediatric melanoma is rare, AST may be treated aggressively with sentinel lymph node biopsy (SLNB) and subsequent completion lymphadenectomy. These procedures have unclear therapeutic benefit and potential morbidity. We aimed to collect outcomes on children with AST treated with excision alone to assist in the management of these lesions. We queried our institution's pathology database for AST specimens submitted between 1994 and 2009. A dermatopathologist reviewed pathology slides to confirm AST diagnosis. Clinical information was obtained from medical records, and outcomes surveys were administered to children with AST. Twenty-nine patients met AST diagnostic criteria and were included in this study. Mean age at first excision was 9.0 ± 4.2 (range 2.3-17.5), and 19 patients underwent more than one excision procedure to achieve clear margins. No patient had SLNB. Fourteen patients (48%) with mean follow-up time of 8.4 years (range 3.5-15.8) completed clinical outcomes surveys. Outcomes with mean follow-up time of 2.8 years (range 0.02-8.1 years) were obtained for 10 additional patients from medical records. There were no reports of recurrence, additional lesions, or metastases in these 24 patients. We report one of the largest series of children with AST treated using excision alone and who remain disease free after a significant follow-up period. Our data suggest that SLNB is not warranted in the routine management of pediatric AST. We recommend complete excision with clear margins and careful clinical follow-up.


Assuntos
Melanoma/patologia , Melanoma/cirurgia , Nevo de Células Epitelioides e Fusiformes/patologia , Nevo de Células Epitelioides e Fusiformes/cirurgia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Diagnóstico Diferencial , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Recidiva Local de Neoplasia/prevenção & controle , Biópsia de Linfonodo Sentinela , Pele/patologia
18.
Ann Plast Surg ; 68(3): 257-60, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21629095

RESUMO

It is not known whether obesity portends poorer outcomes following reduction mammaplasty in adolescent macromastia patients. We review symptoms in obese and nonobese adolescent macromastia patients and describe early outcomes following reduction mammaplasty. Demographics, operative details, and postoperative follow-up data were collected on 67 patients seen at our institution between 1997 and 2008. Variables were compared using 2-sample t tests or Pearson χ/Fisher exact tests. Mean age at surgery was 17.1 ± 1.6 years. Mean body mass index was 27.9 ± 4.5 kg/m, and 32.8% were obese. Thirty-four patients (50.7%) experienced minor complications; 1 patient experienced a major complication. Of patients with complications, obese patients reported a greater number than nonobese patients (P = 0.013). There were no differences in the type of complication or self-reported satisfaction between obese and nonobese patients 34.4 ± 25.7 weeks after surgery. Our findings suggest that reduction mammaplasty is well-tolerated in obese and nonobese adolescents with macromastia and that obesity is not an absolute contraindication to reduction mammaplasty in adolescents.


Assuntos
Hipertrofia/epidemiologia , Hipertrofia/cirurgia , Mamoplastia/estatística & dados numéricos , Obesidade/epidemiologia , Adolescente , Índice de Massa Corporal , Mama/anormalidades , Mama/cirurgia , Comorbidade , Contraindicações , Feminino , Humanos , Satisfação do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Adulto Jovem
19.
J Clin Endocrinol Metab ; 96(11): E1771-81, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21880801

RESUMO

CONTEXT: KISS1 is a candidate gene for GnRH deficiency. OBJECTIVE: Our objective was to identify deleterious mutations in KISS1. PATIENTS AND METHODS: DNA sequencing and assessment of the effects of rare sequence variants (RSV) were conducted in 1025 probands with GnRH-deficient conditions. RESULTS: Fifteen probands harbored 10 heterozygous RSV in KISS1 seen in less than 1% of control subjects. Of the variants that reside within the mature kisspeptin peptide, p.F117L (but not p.S77I, p.Q82K, p.H90D, or p.P110T) reduces inositol phosphate generation. Of the variants that lie within the coding region but outside the mature peptide, p.G35S and p.C53R (but not p.A129V) are predicted in silico to be deleterious. Of the variants that lie outside the coding region, one (g.1-3659C→T) impairs transcription in vitro, and another (c.1-7C→T) lies within the consensus Kozak sequence. Of five probands tested, four had abnormal baseline LH pulse patterns. In mice, testosterone decreases with heterozygous loss of Kiss1 and Kiss1r alleles (wild-type, 274 ± 99, to double heterozygotes, 69 ± 16 ng/dl; r(2) = 0.13; P = 0.03). Kiss1/Kiss1r double-heterozygote males have shorter anogenital distances (13.0 ± 0.2 vs. 15.6 ± 0.2 mm at P34, P < 0.001), females have longer estrous cycles (7.4 ± 0.2 vs. 5.6 ± 0.2 d, P < 0.01), and mating pairs have decreased litter frequency (0.59 ± 0.09 vs. 0.71 ± 0.06 litters/month, P < 0.04) and size (3.5 ± 0.2 vs. 5.4 ± 0.3 pups/litter, P < 0.001) compared with wild-type mice. CONCLUSIONS: Deleterious, heterozygous RSV in KISS1 exist at a low frequency in GnRH-deficient patients as well as in the general population in presumably normal individuals. As in Kiss1(+/-)/Kiss1r(+/-) mice, heterozygous KISS1 variants in humans may work with other genetic and/or environmental factors to cause abnormal reproductive function.


Assuntos
Hormônio Liberador de Gonadotropina/deficiência , Heterozigoto , Kisspeptinas/genética , Fenótipo , Adulto , Animais , Feminino , Genótipo , Humanos , Masculino , Camundongos
20.
Genet Med ; 13(12): 998-1005, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21811163

RESUMO

PURPOSE: : Approximately 5-10% of patients who undergo genetic testing of BRCA1 and BRCA2 receive a variant of unknown significance (VUS) result. The ambiguous nature of a VUS may increase difficulty in patient understanding and decision making regarding risk reduction and surveillance options, including cancer risk-reducing surgeries. VUS reclassification to benign or deleterious may occur in time; however, clinical decisions may need to be made expeditiously, and some patients may pursue irreversible treatments before VUS reclassification. METHODS: : We reviewed the surgical decisions of 107 women postdisclosure of a BRCA VUS result counseled at our institute between 1998 and 2009. CONCLUSION: : Among women receiving a BRCA VUS result at our center, 11 of 107 (10.3%) pursued cancer risk-reducing mastectomy and 22 of 107 (20.6%) pursued cancer risk-reducing bilateral salpingo-oophorectomy. Reclassification of VUS occurred up to 9 years after testing, and 5 of 22 (22.7%) women followed up for 8 or more years continue to have a VUS result. We discuss considerations for providers of genetic services to discuss with patients who receive a VUS result.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Testes Genéticos/normas , Neoplasias Ovarianas/diagnóstico , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Aconselhamento Genético , Heterozigoto , Humanos , Mastectomia , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Ovariectomia , Estudos Prospectivos , Risco , Comportamento de Redução do Risco , Incerteza
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