Height Assessments in Children With Neurofibromatosis Type 1

Soucy, Elizabeth A.; Oppen, Dorothy van; Nejedly, Nicole; Gao, Feng; Gutmann, David H.; Hollander, Abby

doi:10.1177/0883073812446310

Cited by 30 publications

(22 citation statements)

References 23 publications

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“…The only exception was the presence of tumors (several types, see Table S2; excluding those present in the major NF1 criteria), with frequencies similar in index patients fulfilling and not fulfilling the NF1 criteria. Most minor features were found (in index patients fulfilling the NF1 criteria) in a frequency comparable with that described in literature (30,(35)(36)(37)(38). Speaking problems were observed in 16.7%, which is much lower than the 65% previously reported (39).…”

Section: Discussionsupporting

confidence: 79%

A clinical and genetic overview of 18 years neurofibromatosis type 1 molecular diagnostics in the Netherlands

et al. 2013

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NF1 mutations are the underlying cause of neurofibromatosis type 1 (NF1), a neuro-cardio-facio-cutaneous syndrome (NCFC). Because of the clinical overlap between NCFCs, genetic analysis of NF1 is necessary to confirm a clinical diagnosis NF1. This report describes the clinical and genetic findings of 18 years of NF1 molecular diagnostics in the Netherlands. A pathogenic mutation was found in 59.3% (1178/1985) of the index patients, mostly de novo (73.8%). The majority of the index patients (64.3%) fulfilled the National Institute of Health NF1 criteria, a pathogenic mutation was found in 80.9% of these patients. Seventy-four percent of the index patients with an NF1 pathogenic mutation and not fulfilling the NF1 criteria is <12 years, in agreement with the fact that some NF1 symptoms appear after puberty. Genotype-phenotype correlations were studied for 527 index patients. NF1 patients with a type 1 microdeletion have a sixfold higher risk of special education vs NF1 patients with an intragenic mutation. No evidently milder NF1 phenotype for patients with a missense mutation was observed. Forty-six prenatal analyses were performed in 28 (2.4%) families, of which 29 (63%) showed heterozygosity for the familial pathogenic mutation. This indicates that there is a need for prenatal NF1 testing.

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Section: Discussionsupporting

confidence: 79%

A clinical and genetic overview of 18 years neurofibromatosis type 1 molecular diagnostics in the Netherlands

et al. 2013

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“…Short stature, characterised by a height of more than two standard deviations below the predicted mean, is evident in 8–13% of children with NF1 (Szudek et al 2000; Sbidian et al. 2012; Soucy et al 2013) whilst a body height below the third percentile has been observed in 15% of children with NF1 (Clementi et al 1999). …”

Section: Genotype–phenotype Relationships In Patients With Nf1 Microdmentioning

confidence: 99%

Emerging genotype–phenotype relationships in patients with large NF1 deletions

2017

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The most frequent recurring mutations in neurofibromatosis type 1 (NF1) are large deletions encompassing the NF1 gene and its flanking regions (NF1 microdeletions). The majority of these deletions encompass 1.4-Mb and are associated with the loss of 14 protein-coding genes and four microRNA genes. Patients with germline type-1 NF1 microdeletions frequently exhibit dysmorphic facial features, overgrowth/tall-for-age stature, significant delay in cognitive development, large hands and feet, hyperflexibility of joints and muscular hypotonia. Such patients also display significantly more cardiovascular anomalies as compared with patients without large deletions and often exhibit increased numbers of subcutaneous, plexiform and spinal neurofibromas as compared with the general NF1 population. Further, an extremely high burden of internal neurofibromas, characterised by >3000 ml tumour volume, is encountered significantly, more frequently, in non-mosaic NF1 microdeletion patients than in NF1 patients lacking such deletions. NF1 microdeletion patients also have an increased risk of malignant peripheral nerve sheath tumours (MPNSTs); their lifetime MPNST risk is 16–26%, rather higher than that of NF1 patients with intragenic NF1 mutations (8–13%). NF1 microdeletion patients, therefore, represent a high-risk group for the development of MPNSTs, tumours which are very aggressive and difficult to treat. Co-deletion of the SUZ12 gene in addition to NF1 further increases the MPNST risk in NF1 microdeletion patients. Here, we summarise current knowledge about genotype–phenotype relationships in NF1 microdeletion patients and discuss the potential role of the genes located within the NF1 microdeletion interval whose haploinsufficiency may contribute to the more severe clinical phenotype.

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“…Prognosis is generally good, although most children will be below-average height 4 8. Up to 70% of children affected with NF1 will have some learning difficulties, and most will have IQs in the low-average range 9.…”

Section: Answers To the Questions On Pagementioning

confidence: 99%