آشنایی و درک بیماری نوروفیبروماتوز: راهنمایی برای بیماران و والدین

باید از کجا شروع کرد؟ این اطلاعات برای ان دسته از خانواده هایی است که اخیرا به انها گفته شده که یکی از اعضای خانواده به نوروفیبروماتوز مبتلا است. وقتی خود شما نخستین شخصی بودید که این موضوع به او گفته شد در ابتدای امر فقط این واژه را شنیده بودید، همین و بس. همانطور که شوک ناشی از این خبر کمتر میشد می خواستید بیشتر از این اختلال یا اختلالات بدانید. به این دلیل که نوروفیبروماتوز در حقیقت تنها به دلیل یک اختلال نیست این کتابچه به شرح نوروفیبروماتوز و چگونگی علت ان می پردازد و اینکه خانواده شما باید در مورد ان چه اقداماتی انجام دهد و چه کسی به شما کمک خواهد کرد

High incidence of Noonan syndrome features including short stature and pulmonic stenosis in patients carrying NF1 missense mutations affecting p.Arg1809: genotype-phenotype correlation

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype-phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple cafe-au-lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan-like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P<0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1-patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi-exon deletion, providing genetic evidence that p.Arg1809Cys is a loss-of-function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype-phenotype correlation will affect counseling and management of a significant number of patients

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS

Binding of Straight-Chain Saturated Dicarboxylic Acids to Albumin

Dicarboxylic acids are prominent features of several diseases, including Reye&apos;s syndrome. Long-chain dicarboxylic acids have profound effects on the function and structure of isolated mitochondria, suggesting that they could contribute to the mitochondrial dysfunction in Reye&apos;s syndrome. Binding of fatty acids to albumin and the intracellular fatty acid-binding proteins is important in regulating the transport and metabolism of fatty acids and protects against the toxic effects of unbound fatty acids. We studied the binding of dicarboxylic acids to defatted albumin using equilibrium dialysis to assess to what extent dicarboxylic acids are likely to be bound in the plasma of patients. Dicarboxylic acids bind weakly to albumin in a molar ratio of 3.8, 4.2, 1.6, 0.8, and 0.7 to 1 for octadecanedioic, hexadecanedioic, tetradecanedioic, dodecanedioic, and decanedioic acid, respectively. The dissociation constants for long-chain dicarboxylic acids are 100-1,000-fold larger than those of comparable monocarboxylic acids. Oleate competes with dicarboxylic acid and reduces the moles of dicarboxylic acid bound per mol of albumin to &lt; 1. Octanoate inhibits dicarboxylic acid binding. Our observations indicate that in Reye&apos;s syndrome, substantial concentrations of dicarboxylic acids of patients may be free and potentially toxic to mitochondria and other cellular processes

Bone mineral density in children and young adults with neurofibromatosis type 1

Concern for impaired bone health in children with neurofibromatosis type 1 (NF-1) has led to increased interest in bone densitometry in this population. Our study assessed bone mineral apparent density (BMAD) and whole-body bone mineral content (BMC)/height in pediatric patients with NF-1 with a high plexiform neurofibroma burden. Sixty-nine patients with NF-1 (age range 5.2–24.8; mean 13.7±4.8 years) were studied. Hologic dual-energy X-ray absorptiometry scans (Hologic, Inc., Bedford, MA, USA) were performed on all patients. BMD was normalized to derive a reference volume by correcting for height through the use of the BMAD, as well as the BMC. BMAD of the lumbar spine (LS 2–4), femoral neck (FN), and total body BMC/height were measured and Z-scores were calculated. Impaired bone mineral density was defined as a Z-score ≤−2. Forty-seven percent of patients exhibited impaired bone mineral density at any bone site, with 36% at the LS, 18% at the FN, and 20% total BMC/height. BMAD Z-scores of the LS (−1.60±1.26) were more impaired compared with both the FN (−0.54±1.58; P=0.0003) and the whole-body BMC/height Z-scores (−1.16±0.90; P=0.036). Plexiform neurofibroma burden was negatively correlated with LS BMAD (r(s)=−0.36, P=0.01). In pediatric and young adult patients with NF-1, LS BMAD was more severely affected than the FN BMAD or whole-body BMC/height