SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
A total of 37 girls with a history of benign premature pubarche were followed into puberty; a disproportionate number of girls experienced early menarche. Twenty-five had some degree of acne, 14 had hirsutism, and 5 had acanthosis nigricans. Body mass index (BMI) at initial presentation correlated with postpubertal BMI and was weakly correlated with postpubertal hirsutism.
Obesity is associated with a number of dermatoses. It affects cutaneous sensation, temperature regulation, foot shape, and vasculature. Acanthosis nigricans is the most common dermatological manifestation of obesity. Skin tags are more commonly associated with diabetes than with obesity. Obesity increases the incidence of cutaneous infections that include: candidiasis, intertigo, candida folliculitis, furunculosis, erythrasma, tinea cruris, and folliculitis. Less common infections include cellulitis, necrotizing fasciitis, and gas gangrene. Leg ulcerations, lymphedema, plantar hyperkeratosis, and striae are more common with obesity. Hormonal abnormalities and genetic syndromes (Prader-Willi) are related to obesity and its dermatoses; however, cellulite is not related to obesity.
OBJECTIVE: We sought to describe the clinical characteristics and complications of children with acquired lipodystrophy (LD). METHODS: We conducted a retrospective chart review at a tertiary, academic children's hospital of children clinically given a diagnosis of acquired LD between January 1997 and December 2004. RESULTS: During the study period, 23 patients were identified. Their mean age at diagnosis was 9.74 +/- 3.98 years. Of patients, 61% were girls. The length of the follow-up was 4.8 +/- 3.5 years from the time of LD diagnosis. Of patients, 30% had evidence of localized disease (7 of 23), 26% (6 of 23) had localized partial disease, and 44% (10 of 23) had generalized LD. The most common underlying diagnosis was dermatomyositis (78%), alone or in association with other autoimmune diseases (juvenile rheumatoid arthritis 17%). Panniculitis with autoimmunity was noted in 17% of the patients. More than half of the patients had at least one complication attributable to LD such as acanthosis nigricans (22%), hyperpigmentation (22%), hepatomegaly (13%), hypertension (13%), protuberant abdomen (9%), and hyperlipidemia (4%). The only predictor for development of complications was the age of diagnosis of LD, with younger age being associated with increased risk (7 vs 12 years, P = .04). LIMITATIONS: Limitations were inherent to the retrospective design. CONCLUSIONS: Childhood acquired LD is seen more frequently in the context of autoimmunity. Affected children should be monitored for the development of complications, particularly if given a diagnosis of LD at a younger age.
Here, we show that the energetics of transmembrane helix heterodimer formation can be characterized in liposomes using Förster resonance energy transfer (FRET). We present the theory and the protocol for measuring the free energy of heterodimerization, and the total (hetero and homo-dimeric) dimer fraction. We use the presented methodology to determine the propensity for heterodimer formation between wild-type fibroblast growth factor receptor 3 (FGFR3) transmembrane domain and the Ala391Glu mutant, linked to Crouzon syndrome with acanthosis nigricans.
PURPOSE: To report a case of systemic corticosteroid toxicity resulting from topical and periocular therapy. METHODS: Treatment and follow-up of an 11-year-old male with uveitis are illustrated. Initial presentation of the patient was bilateral iridocyclitis, for which he was treated with prednisolone acetate 1% every 2 hours for 6 months. Subsequently, posterior uveitis developed, necessitating posterior subtenon injections. RESULTS: After initial topical corticosteroid therapy, the patient developed a cushingoid habitus accompanied by increased lanugo hair, acanthosis nigricans, posterior subcapsular lens opacities, and increased intraocular pressure. Cushingoid stigmata worsened after administration of posterior subtenon injection of corticosteroids. The patient's truncal obesity worsened, and his linear growth stopped. CONCLUSIONS: Systemic toxic effects may develop as a result of topical and local use of ophthalmic corticosteroid preparations in susceptible patients.
We describe 8 patients affected with Costello syndrome including an affected sib pair and review the literature on 29 previously reported cases. We emphasize an association with advanced parental age, which is consistent with autosomal dominant inheritance with germline mosaicism. The pathogenesis appears to involve metabolic dysfunction, with growth disturbance, storage disorder appearance, acanthosis nigricans, hypertrophic cardiomyopathy, and occasional abnormalities of glucose metabolism. Although the cause is currently unknown, Costello syndrome is interesting because of a potential genetic-metabolic etiology.
Becker's nevus is an uncommon, unilateral, hyperpigmented, hairy cutaneous hamartoma which usually begins in adolescence. Its clinical features and its occurrence mainly in male individuals suggest that androgen stimulation may play a role in its pathogenesis. Androgen receptor assays were performed in a 16-year-old patient with a Becker's nevus. The patient coincidentally had acanthosis nigricans. Lesional tissue showed an androgen receptor level of 634.1 fm/mg protein. A specimen from the contralateral left pectoral area showed no dectectable androgen receptor activity (less than 2.0 fm/mg protein). These results suggest that exquisite androgen sensitivity and stimulation may explain the clinical manifestations of Becker's nevus.
This series describes some common and uncommon cutaneous findings in twelve patients with ataxia-telangiectasia (A-T). All patients had the characteristic telangiectasia as described previously. However, the telangiectases did not conform to a classic photodistribution . Our series did include one patient with a pathologic reaction to light-simulating hydroa aestivale or vacciniforme . In addition, there were three patients with acanthosis nigricans in two unrelated families. Vitiligo, impetigo, recurrent herpetic gingivostomatitis, hirsutism, lipoatrophy, gray hair, progeroid changes and hyper- and hypopigmented macules were noted in our patients. Many of our patients had one or more caf'e au lait like-lesions in a dermatomal distribution. In addition, several of the family members showed one or more café au lait-like lesions, suggesting the possibility that this finding may represent a phenotypic expression in the skin of carriers of this cancer-prone syndrome.
The sign of Leser-Trélat is rare. It is defined as the sudden eruption of multiple seborrheic keratoses caused by a malignancy. Because both seborrheic keratoses and cancer are common in the elderly, it is not always easy to tell from the literature or in any given patient if this sign is present. In fact, its validity has been questioned. Its association with malignant acanthosis nigricans is one of several of its features that support its legitimacy as a true paraneoplastic disorder.
This article concentrates on the major signs and syndromes that are associated with internal malignancies in the geriatric population. Included are cutaneous metastases, ectopic adrenocorticotropic hormone-producing syndromes, and disorders arising from APUD cell tumors. The major paraneoplastic disorders of dermatomyositis, generalized pruritus, Bazex's syndrome, and acanthosis nigricans also are discussed. Also included are Bowen's disease of skin; arsenical toxicity; and the Peutz-Jeghers', Gardner's, and Torre's syndromes, which are indicative of systemic or organ-related carcinogens.
Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome (BSCL), is a rare autosomal recessive disease characterized by a near-absence of adipose tissue from birth or early infancy and severe insulin resistance. Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia. A locus (BSCL1) has been mapped to 9q34 with evidence of heterogeneity. Here, we report a genome screen of nine BSCL families from two geographical clusters (in Lebanon and Norway). We identified a new disease locus, designated BSCL2, within the 2.5-Mb interval flanked by markers D11S4076 and D11S480 on chromosome 11q13. Analysis of 20 additional families of various ethnic origins led to the identification of 11 families in which the disease cosegregates with the 11q13 locus; the remaining families provide confirmation of linkage to 9q34. Sequence analysis of genes located in the 11q13 interval disclosed mutations in a gene homologous to the murine guanine nucleotide-binding protein (G protein), gamma3-linked gene (Gng3lg) in all BSCL2-linked families. BSCL2 is most highly expressed in brain and testis and encodes a protein (which we have called seipin) of unknown function. Most of the variants are null mutations and probably result in a severe disruption of the protein. These findings are of general importance for understanding the molecular mechanisms underlying regulation of body fat distribution and insulin resistance.
OBJECTIVES: To test the hypothesis that the triad of hyperandrogenism, insulin resistance and acanthosis nigricans (HAIRAN syndrome) in the presence of obesity, also known as type C insulin resistance, is caused by mutations in the gene for peroxisome proliferator activated receptor gamma (PPARgamma), a receptor for the thiazolidinedione drugs that enhance sensitivity to insulin. To investigate possible correlations between mutations in PPARgamma and the degree of insulin resistance. DESIGN: A candidate gene approach to study the molecular basis for a syndrome of obesity; a comparison of genotype with in vivo phenotype. PATIENTS: Fifteen unrelated patients with HAIRAN syndrome and obesity. Controls for the gene analysis: 25 unrelated non-diabetic non-obese individuals. Controls for the metabolic studies: six unrelated patients with type 2 diabetes mellitus and nine unrelated non-diabetic non-obese individuals. MEASUREMENTS: Analysis of polymerase chain reaction (PCR) products of the 7 exons that constitute the entire coding region of both PPARgamma isoforms (PPARgamma1 and PPARgamma2) for single-stranded conformational polymorphisms (SSCP); in exons with variant patterns: restriction fragment length polymorphism (RFLP) analysis; and, where relevant, direct sequencing. Evaluation of insulin resistance using the insulin euglycaemic clamp technique. RESULTS: A synonymous substitution in codon 477 (CACHis --> CATHis) was found in one patient. A missense mutation in codon 12 of PPARgamma2 (CCAPro --> GCAAla) was found in another patient, but not in any of 25 non-diabetic, non-obese control individuals. The patient with the Pro12Ala variant had the highest steady state glucose infusion rate (SSGIR) and most marked suppression of hepatic glucose production rate (HGPR) of all of the patients studied. CONCLUSIONS: Mutations in the PPARgamma gene are unlikely to be major contributors to HAIRAN syndrome with obesity. The Pro12Ala variant may correlate with a lesser degree of insulin resistance in these patients.
AIMS: Type 2 diabetes mellitus has never previously been described in UK children, although an increasing incidence in childhood is recognized in international studies. The prevalence of obesity in UK children is increasing and is a recognized risk factor for the development of diabetes. The aim of this study was to identify and characterize children with Type 2 diabetes in the West Midlands and Leicester. METHODS: Children were identified by contacting paediatricians responsible for diabetes in five hospitals. Details were collected on demographics, mode of presentation, investigations and treatment on a standard proforma. RESULTS: Eight girls were identified with Type 2 diabetes, aged 9-16 years and who were of Pakistani, Indian or Arabic origin. They were all overweight (percentage weight for height 141-209%) and had a family history of diabetes in at least two generations. They presented insidiously with hyperglycaemia and glycosuria without ketosis and five were asymptomatic. Islet cell antibodies measured in seven patients were negative. Four had acanthosis nigricans which is a cutaneous marker of insulin resistance and the other four had high plasma levels of insulin and/or C peptide. These patients are distinct from those with maturity-onset diabetes of the young (MODY). All were initially managed with dietary measures, seven have been treated with oral anti-diabetic agents of whom two have subsequently required insulin. CONCLUSIONS: These are the first UK case reports of Type 2 diabetes in children. Paediatricians need to be aware of the risk of Type 2 diabetes developing in childhood in high-risk ethnic groups, particularly in association with obesity and a positive family history.
We report two black adolescent subjects who presented with diabetic ketoacidosis, but who lacked autoimmune markers and demonstrated clinical and biochemical characteristics more typical of Type 2 diabetes, including obesity, acanthosis nigricans, positive family history for Type 2 diabetes, and Type 2 diabetic dyslipidaemia. Subsequent to acute presentation, insulin was discontinued in both subjects and excellent glycaemic control was achieved with metformin therapy alone. Four months following acute presentation, both had adequate C-peptide responses to intravenous glucagon. Type 2 diabetes can present as diabetic ketoacidosis in obese adolescent subjects.
AIM: To present the clinical features of Type 2 diabetes mellitus (T2DM) in overweight European Caucasian children and adolescents. METHODS: We report the clinical characteristics of 16 non-syndromal overweight European Caucasian adolescents with T2DM (10 boys, 6 girls, SDS-BMI in median +2.8, range +1.6 to +3.4) treated in 5 specialised centres for obesity and diabetes. RESULTS: None of the adolescents manifested with ketoacidosis. 13 were asymptomatic (3 adolescents with polyuria), 12 showed features of metabolic syndrome (dyslipidaemia or hypertension), 8 demonstrated acanthosis nigricans and 12 had relatives with T2DM. 11 adolescents were extremely obese and all patients were pubertal. Mean age at diagnosis was 14.2 years (range 11.0 - 16.9). Median insulin was 19 microU/ml, insulin resistance index (HOMA) 8.5, C-peptide 2.3 ng/ml, HbA1c 6.9 %, fasting blood glucose 176 mg/dl and blood glucose at 2 hours with the oGTT 229 mg/dl at manifestation. Fasting blood glucose and HBA1c were in the normal range in 4 and 6 adolescents respectively, while oGTT always fitted the diagnosis of T2DM. CONCLUSION: Since T2DM occurred in Caucasian overweight adolescents and is frequently asymptomatic, it is essential that clinicians perform diagnostic procedures to identify T2DM in high-risk groups of overweight Caucasian adolescents (extreme obesity, features of metabolic syndrome, relatives with T2DM).
This is what we believe to be the first report of the sign of Leser-Trélat in association with occult adenocarcinoma of the lung. The sign of Leser-Trélat is proposed as a sign of possible occult malignancy, despite various suggestions to the contrary. Also, it is suggested that a tumor-produced humoral factor (eg, transforming growth factor-alpha [TGF-alpha]) could be responsible for both the acute eruption of the monomorphous seborrheic keratoses and the nearly concomitant development of acanthosis nigricans, which occurred in our case. The possible distinction between a hyperplastic and a neoplastic origin of various types of seborrheic keratosis is discussed in relation to this hypothetical humoral factor. In addition, we suggest a refinement of the definition of the sign of Leser-Trélat and discuss the use of "sign of Leser-Trélat" and "syndrome of Leser-Trélat" in relation to physical findings. All patients with the sign of Leser-Trélat should undergo a thorough evaluation for occult malignancy.
The polycystic ovary syndrome is a common cause of anovulatory infertility. Women with severe insulin resistance are a unique subset of polycystic ovary syndrome. The syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN syndrome) is one presentation of the insulin-resistant subset of polycystic ovary syndrome. Insulin resistance and hyperandrogenism are caused by genetic and environmental factors. In women with anovulatory infertility caused by hyperandrogenism and insulin resistance, clomiphene citrate treatment often fails to result in pregnancy. For these women, weight loss and insulin sensitizers can be effective methods of inducing ovulation and pregnancy and may reduce the number of clomiphene-resistant women with polycystic ovary syndrome who are treated with gonadotropins, ovarian surgery, or in vitro fertilization-embryo transfer.
Several gain-of-function mutations in a receptor tyrosine kinase, fibroblast growth factor receptor 3 (FGFR3), cause dwarfism in humans. Two particularly severe dwarfisms, thanatophoric dysplasia type II (TDII) and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), are associated with glutamic acid (E) and methionine (M) substitutions at the K650 residue in the kinase domain. TDII is lethal at birth, whereas most of the SADDAN patients survive the perinatal period. However, FGFR3 with the SADDAN mutation is more activated than FGFR3 with the TDII mutation in vitro. To find out whether the K650M mutation also causes the SADDAN phenotype, we introduced the corresponding point mutation (K644M) into the mouse Fgfr3 gene. Heterozygous mutant mice show a phenotype similar to human SADDAN, e.g. the majority of the SADDAN mice survive the perinatal period. This suggests that the survival of SADDAN patients is indeed attributed to the K650M mutation in FGFR3. The long bone abnormalities in SADDAN mice are milder than the TDII model. In addition, overgrowth of the cartilaginous tissues is observed in the rib cartilage, trachea and nasal septum. The FGF ligand at the low concentration differentially activates Map kinase in primary chondrocyte cultures from wild-type and SADDAN mice. Comparisons of the molecular bases of the phenotypic differences in SADDAN and TDII mice may increase our understanding of the factors that influence the severity in these two related skeletal dysplasias.