Neurofibromatosis in Children: The Role of the Orthopaedist

Crawford, Alvin H.; Schorry, Elizabeth K.

doi:10.5435/00124635-199907000-00002

Cited by 155 publications

(123 citation statements)

References 46 publications

Supporting

Mentioning

118

Contrasting

Unclassified

Order By: Relevance

“…People with NF1 are constitutionally heterozygous for an NF1 loss-of-function mutation, that is, they are haploinsufficient for NF1. The skeleton is frequently affected in patients with NF1 [Crawford and Schorry, 1999]. Manifestations include focal bony lesions associated with significant morbidity, mild shortness of stature and reduced bone mineral density (BMD).…”

Section: Introductionmentioning

confidence: 99%

Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options

Elefteriou

Kolanczyk

Schindeler

et al. 2009

American J of Med Genetics Pt A

Self Cite

138

114

View full text Add to dashboard Cite

The skeleton is frequently affected in individuals with neurofibromatosis type 1, and some of these bone manifestations can result in significant morbidity. The natural history and pathogenesis of the skeletal abnormalities of this disorder are poorly understood and consequently therapeutic options for these manifestations are currently limited. The Children's Tumor Foundation convened an International Neurofibromatosis Type 1 Bone Abnormalities Consortium to address future directions for clinical trials in skeletal abnormalities associated with this disorder. This report reviews the clinical skeletal manifestations and available preclinical mouse models and summarizes key issues that present barriers to optimal clinical management of skeletal abnormalities in neurofibromatosis type 1. These concepts should help advance optimal clinical management of the skeletal abnormalities in this disease and address major difficulties encountered for the design of clinical trials. © 2009 Wiley‐Liss, Inc.

show abstract

Section: Introductionmentioning

confidence: 99%

Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options

Elefteriou

Kolanczyk

Schindeler

et al. 2009

American J of Med Genetics Pt A

Self Cite

138

114

View full text Add to dashboard Cite

show abstract

“…4,5 Probably the most characteristic skeletal abnormality observed in young children with NF1 is long bone dysplasia. The usual clinical presentation in infancy or early childhood is anterolateral bowing of the tibia, with the apex near the junction of the middle and distal thirds of the tibia (Fig.…”

mentioning

confidence: 99%

The use of anterolateral bowing of the lower leg in the diagnostic criteria for neurofibromatosis type 1

Stevenson

Viskochil

Schorry³

et al. 2007

Genetics in Medicine

Self Cite

View full text Add to dashboard Cite

Neurofibromatosis type 1 is diagnosed clinically based on the presence of two of seven criteria developed by a panel of experts in 1987. The sixth criterion focuses on skeletal findings and is as follows: "A distinctive osseous lesion such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudarthrosis." The wording for this criterion is misleading. In particular, "thinning of long bone cortex" is not the characteristic radiographic presentation, and no mention of long bone bowing is included. The distinctive clinical feature of long bone dysplasia in neurofibromatosis type 1 is anterolateral bowing of the lower leg (portion of the body delimited by the knee and ankle). The usual radiographic findings of long bone dysplasia in neurofibromatosis type 1 at first presentation, prior to fracture, are anterolateral bowing with medullary canal narrowing and cortical thickening at the apex of the bowing. We suggest that anterolateral bowing of the lower leg, with or without fracture or pseudarthrosis, is a more appropriate description of the primary finding that a clinician will use to fulfill the sixth diagnostic criterion for neurofibromatosis type 1. Clarification of this diagnostic criterion is important for the clinician and for research protocols. Appropriate interpretation will improve understanding of the natural history and pathophysiology of neurofibromatosis type 1. Genet Med 2007:9(7):409-412.

show abstract

“…Other skeletal complications occur with a great deal of variability of expression; some such as tibial dysplasia/pseudarthrosis occur very rarely, with an incidence of only 3-5% of NF1 patients. Scoliosis occurs in between 15% and 30% of NF1 patients, depending on the type of population surveyed [Crawford and Schorry, 1999]. Pectus deformities of the chest wall appear quite common in NF1, particularly when one looks for subtle manifestations.…”

Section: Discussionmentioning

confidence: 99%

Variable expression of neurofibromatosis 1 in monozygotic twins

Rieley

Stevenson

Viskochil

et al. 2011

American J of Med Genetics Pt A

Self Cite

View full text Add to dashboard Cite

Neurofibromatosis 1 (NF1) is a common autosomal dominant disorder with high penetrance but extreme variability of expression. Monozygotic (MZ) twins with NF1 who have phenotypic discordances are a useful tool in evaluating which traits are influenced by non-hereditary influences such as second hit somatic events, environmental agents, epigenetic modification, or post-zygotic mutations. We evaluated nine sets of MZ twins and one set of MZ triplets, ages 4-18 years, for NF1 features and calculated probandwise concordance (P C ) for each feature. MZ twins were highly concordant in numbers of cafe-au-lait spots (P C ¼ 0.89) and cutaneous neurofibromas. IQ scores were within 10 points for all twin pairs tested, and similar patterns of learning disabilities and speech disorders were observed. Twin pairs showed significant discordance for tumors, particularly plexiform neurofibromas (P C ¼ 0.40) and malignant peripheral nerves sheath tumors (MPNST), as expected if post-natal second -hit events were contributing to these features. One set of twins was concordant for multiple, large paraspinal neurofibromas, suggesting that there may be more hereditary factors involved in production of paraspinal neurofibromas. Four sets were concordant for pectus deformities of the chest (P C ¼ 0.80). Three sets of twins were discordant for scoliosis (P C ¼ 0.40); an additional set was concordant for scoliosis but differed in presence of dystrophic features and need for surgery. Our data suggest there are additional non-hereditary factors modifying the NF1 phenotype and causing discordancies between MZ twins. Future studies may focus on differences in epigenetic changes or somatic mosaicism which have been documented for other disease genes in MZ twins.

show abstract

Neurofibromatosis in Children: The Role of the Orthopaedist

Cited by 155 publications

References 46 publications

Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options

Skeletal abnormalities in neurofibromatosis type 1: Approaches to therapeutic options

The use of anterolateral bowing of the lower leg in the diagnostic criteria for neurofibromatosis type 1

Variable expression of neurofibromatosis 1 in monozygotic twins

Contact Info

Product

Resources

About