Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Riccardi, Claudia; Perrone, Lorena; Napolitano, Filomena; Sampaolo, Simone; Melone, Mariarosa Anna Beatrice

doi:10.3390/cancers12102965

Cited by 16 publications

(19 citation statements)

References 450 publications

(586 reference statements)

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“…To quantify the dietary intake of calcium and vitamin D a FFQ (food frequency questionnaire) was administered to the patients and controls; we asked them if they assumed calcium-rich foods/vitamin D-rich foods and how often they did it, so we were able to quantify the amount of their daily calcium and vitamin D intake 24 , 25 .…”

Section: Methodsmentioning

confidence: 99%

Bone metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity

Ferrara

Tortora

Rosano

et al. 2022

Sci Rep

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Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and z-score data obtained at Dual-Energy X-ray Absorptiometry (DXA) during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced z-score at DXA (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z-score (p < 0.001). We speculated that a combination of different factors, including reduced sun exposure, possibly associated with reduced serum vitamin D levels, and poor physical activity, concur to the impaired bone status in NF1 patients. We also demonstrated that treatment with vitamin D can be effective in improving z-score value in NF1 patients, including children. In conclusion, the findings of the current study are expected to have important implications for the follow-up and prevention of osteopenia/osteoporosis in this common genetic disease.

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Section: Methodsmentioning

confidence: 99%

Bone metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity

Ferrara

Tortora

Rosano

et al. 2022

Sci Rep

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“…Moreover, the epigenetic regulator can also provide a potential target when dealing with different phenotypes (117). ( 2 120). Collectively, these observations confirmed the impact of critical epigenetic, mosaic, and environmental elements on the pathogenesis of neurofibromas or other features.…”

Section: Discussionmentioning

confidence: 64%

“…Appropriate genetic counseling is needed as gonadal mosaicism can lead to complete NF1 manifestations in offspring ( 119 ). (3) Environment, such as hormone and vitamin D ( 12 , 120 ). Collectively, these observations confirmed the impact of critical epigenetic, mosaic, and environmental elements on the pathogenesis of neurofibromas or other features.…”

Section: Discussionmentioning

confidence: 99%

Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1

et al. 2021

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Neurofibromatosis type 1 (NF1) is a tumor predisposition genetic disorder that directly affects more than 1 in 3,000 individuals worldwide. It results from mutations of the NF1 gene and shows almost complete penetrance. NF1 patients show high phenotypic variabilities, including cafe-au-lait macules, freckling, or other neoplastic or non-neoplastic features. Understanding the underlying mechanisms of the diversities of clinical symptoms might contribute to the development of personalized healthcare for NF1 patients. Currently, studies have shown that the different types of mutations in the NF1 gene might correlate with this phenomenon. In addition, genetic modifiers are responsible for the different clinical features. In this review, we summarize different genetic mutations of the NF1 gene and related genetic modifiers. More importantly, we focus on the genotype–phenotype correlation. This review suggests a novel aspect to explain the underlying mechanisms of phenotypic heterogeneity of NF1 and provides suggestions for possible novel therapeutic targets to prevent or delay the onset and development of different manifestations of NF1.

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“…The Food and Drug Administration approved selumetinib therapy for use in children patients with inoperable NF1-associated plexiform neurofibromas in 2019[ 25 ]. Diagnosis of NF1 in a parent may permit equivocal diagnosis of NF1 in a child, is essential for genetic counseling, and has important medical implications for the affected parent[ 26 ]. Vitamin D or its analogues have been used to treat both skin and bone lesions in NF1 patients, either alone or combined with other therapeutic agents[ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Familial left cervical neurofibromatosis 1 with scoliosis: A case report

Mu¹,

Zhang²,

Shen³

et al. 2021

WJCC

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BACKGROUND Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder affecting many parts of the body with café au lait spots, skeletal deformity, and scoliosis. A familial case of NF1 with scoliosis and a painless mass had not yet been reported. CASE SUMMARY We describe the case of a 15-year-old male patient with a painless lump on the left side of his neck for 10 years and scoliosis. His right shoulder was about 5 cm lower than the left, the left side of his face was deformed, and the left submandibular skin was relaxed. The folding and drooping were obvious and movement was poor. Computed tomography revealed the involvement of the neck, upper chest wall, and surrounding left shoulder, accompanied by bone changes and scoliosis. Histological evaluation showed subepidermal pale blue mucoid degeneration, fibrous fusiform cells in the dermis in a fascicular, woven arrangement. His mother had the same medical history. The diagnosis was neurofibromatosis of the left neck. Various parts of the tumor tissue were serially resected during several visits. Eight months after surgery, there was a slight tendency to regrow. CONCLUSION This case of slow-progressing NF1 highlights the importance of early diagnosis and treatment to reduce its impact on the patient’s growth and development.

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Understanding the Biological Activities of Vitamin D in Type 1 Neurofibromatosis: New Insights into Disease Pathogenesis and Therapeutic Design

Cited by 16 publications

References 450 publications

Bone metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity

Bone metabolism in patients with type 1 neurofibromatosis: key role of sun exposure and physical activity

Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1

Familial left cervical neurofibromatosis 1 with scoliosis: A case report

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