Annual review of children with neurofibromatosis type 1

Dunning-Davies, B M; Parker, Alasdair

doi:10.1136/archdischild-2014-308084

Cited by 35 publications

(31 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CALMs are usually the first clinical indication for suspected NF1. Typically, the characteristic CALMs in individuals with NF1 are ovoid in shape, with well-defined borders, uniform in color, and about 1–3 cm in size [13]. Genetically confirmed NF1 children presented with typical CALMs in this study and in our previous study [5].…”

Section: Discussionsupporting

confidence: 69%

Clinical Presentation and Novel Pathogenic Variants among 68 Chinese Neurofibromatosis 1 Children

Yao

et al. 2019

Genes

View full text Add to dashboard Cite

Background: Neurofibromatosis 1 (NF1) is one of the most common dominantly inherited genetic disorders worldwide, with an age-dependent phenotypic expression. Exploring the mutational spectrum and clinical presentation of NF1 patients at different ages from a diverse population will aid the understanding of genotype–phenotype correlations. Methods: In this study, 95 Chinese children with clinical suspicion of NF1 mainly due to the presence of multiple café-au-lait macules (CALMs) were subjected to medical exome-sequencing analysis and Sanger confirmation of pathogenic variants. Clinical presentations were evaluated regarding dermatological, ocular, neurological, and behavioral features. Results: Pathogenic or likely pathogenic NF1 variants were detected in 71.6% (68/95) of patients; 20 pathogenic variants were not previously reported, indicating that Chinese NF1 patients are still understudied. Parental Sanger sequencing confirmation revealed 77.9% of de novo variants, a percentage that was much higher than expected. The presence of a higher number of NF1-related features at young ages was correlated with positive diagnostic findings. In addition to CALMs, neurological and behavioral features had a high expression among Chinese NF1 children. We attempted to correlate short stature with the locations of the pathogenic variants across the NF1 gene. It is interesting to notice that variants detected in the C-terminal region of the NF1 gene were less likely to be associated with short stature among the NF1 patients, whereas variants at the N-terminal were highly penetrant for the short stature phenotype. Conclusion: Novel NF1 pathogenic variants are yet to be uncovered in under-studied NF1 patient populations; their identification will help to reveal novel genotype–phenotype correlations.

show abstract

Section: Discussionsupporting

confidence: 69%

Clinical Presentation and Novel Pathogenic Variants among 68 Chinese Neurofibromatosis 1 Children

Yao

et al. 2019

Genes

View full text Add to dashboard Cite

show abstract

“…Especially, altered RAS-MAPK signaling has been identified as a key pathway in regulation of growth plate chondrogenesis and is affected in several disorders, referred to as RASopathies [33]. These conditions include Coffin-Lowry syndrome [9–10], Costello (faciocutaneoskeletal syndrome) [11], multiple lentigines syndrome (LEOPARD syndrome) [12–16], neurofibromatosis type 1 [17–18], and Noonan Syndrome or Noonan-like syndrome [11, 19–20]. Patients with these disorders have overlapping phenotypes of short stature, skin manifestation, cardiovascular abnormalities, and variable degree of learning disability/cognitive dysfunction and/or predisposition to cancers.…”

Section: Genetics Of Short Staturementioning

confidence: 99%

Genetics of Short Stature

Jee¹,

Andrade

Baron³

et al. 2017

Endocrinology and Metabolism Clinics of North America

View full text Add to dashboard Cite

Synopsis Short stature is a common and heterogeneous condition which is often genetic in etiology. For most children with genetic short stature, the specific molecular causes remain unknown, but with advances in exome/genome sequencing and bioinformatics approaches, new genetic causes of growth disorders have been identified, contributing to the understanding of the underlying molecular mechanisms of longitudinal bone growth and growth failure. These genetic causes can involve not only hormonal deficiencies, including the growth hormone-IGF-1 axis, thyroid hormone or glucocorticoid and defects in hormonal receptors or subsequent signaling, but also defects in fundamental cellular processes (intracellular signaling pathways, transcriptional regulation, and DNA repair), extracellular matrix, or paracrine signaling. Especially, heterozygous and/or mild mutations in SHOX, NPR2, ACAN, IGF1, IGF1R, or FGFR3 have been associated with isolated short stature without other prominent or noticeable phenotype while homozygous and/or severe mutations in these genes cause severe short stature with bone malformation, that is, a chondrodysplasia. Identifying new genetic causes of growth disorders has the potential to improve diagnosis, prognostic accuracy, individualized management, and help avoid unnecessary testing for endocrine and other disorders.

show abstract

“…The pathoetiology of the multiple manifestations found in this disease across different organ systems is complex. 1 NF1 has an autosomal dominant pattern of inheritance, high clinical variability, complete penetrance, and age-dependent complications. 2 In addition to neurofibromas, there are numerous other clinical manifestations in NF1, such as gliomas, peripheral nerve sheath tumors, and other malignant tumors as well as nontumor effects that include skeletal dysplasia and learning disabilities.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of denosumab therapy for neurofibromatosis type I with osteoporosis and history of fractures: a case report

Uehara

Nakamura

Takahashi

et al. 2018

TCRM

View full text Add to dashboard Cite

BackgroundThe natural history and pathogenesis of the skeletal abnormalities found in neurofibromatosis type 1 (NF1) are poorly understood, and the therapeutic options for these manifestations remain limited. This report first describes the clinical outcomes of denosumab treatment for a patient with NF1 suffering from osteoporosis.MethodsWe enrolled a patient with NF1 under denosumab treatment for osteoporosis, prior fractures, and no improvement in bone mineral density (BMD) over 3 years of alendronate therapy. BMD was monitored by dual-energy X-ray absorptiometry. Tested laboratory data included bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, tartrate-resistant acid phosphatase 5b, 1-alpha, 25-dihydroxyvitamin D3, and parathyroid hormone. BMD and laboratory data were evaluated before, between 2 and 4 months, and at 6, 12, 18, and 24 months of treatment.Case presentationDuring 2 years of denosumab therapy for osteoporosis in a 58-year-old female NF1 patient with prior fractures, BMD increased by 6.5% in the lumbar spine and 10.6% in the total hips, and bone turnover markers were notably improved. No fractures occurred during the latter half of treatment.ConclusionDenosumab represents an effective treatment option for osteoporosis in NF1 patients.

show abstract

Annual review of children with neurofibromatosis type 1

Cited by 35 publications

References 18 publications

Clinical Presentation and Novel Pathogenic Variants among 68 Chinese Neurofibromatosis 1 Children

Clinical Presentation and Novel Pathogenic Variants among 68 Chinese Neurofibromatosis 1 Children

Genetics of Short Stature

Efficacy of denosumab therapy for neurofibromatosis type I with osteoporosis and history of fractures: a case report

Contact Info

Product

Resources

About