Diagnosis and management of neurofibromatosis type 1 in Arabian Gulf Cooperation Council Region: challenges and recommendations

Abstract

Neurofibromatosis type 1 (NF1) is a complex multisystem genetic disorder that requires long-term, age-specific monitoring and multidisciplinary care. NF1 symptom burden can significantly affect the quality of life and impose a substantial economic burden on patients and their families. The approval and widespread availability of mitogen-activated protein kinase (MEK) inhibitors such as selumetinib for NF1-related plexiform neurofibromas have revolutionized the standard of care for patients with NF1, however their effective utilization hinges on early recognition of NF1. We present a consensus manuscript describing the challenges observed in the Arabian Gulf Cooperation Council (GCC) for diagnosing and managing NF1. Experts from the GCC also present recommendations for the early recognition and management of NF1 and its complications. A referral pathway that can play a crucial role in helping primary healthcare providers refer their patients to experts is also proposed. Increasing the availability and accessibility of genetic testing at an affordable cost and optimizing personalized NF1 care are essential for NF1 management. Developing regional guidelines for NF1 management and establishing NF1 centers of excellence may facilitate better care and outcomes for patients with NF1 in the GCC region.

Keywords: Gulf Cooperation Council; children; management; neurofibromatosis type 1; referral.

Figure 1

Differential diagnosis of patients with CALM. [Source: Miller et al, 2019 (35)]. BS, Bloom syndrome; CALM, café-au-lait macules; FS, Fanconi syndrome; CMMRD, constitutional mismatch repair deficiency; OPG, optical pathway glioma; PTEN, phosphatase and tensin homolog; UV, ultraviolet.

Figure 2

Overview of frequency of clinical and developmental assessments in patients with NF1. [Source: Bergqvist et al, 2020 (1); Miller et al., 2019 (35)]. ADD, attention-deficit disorder; MRI, magnetic resonance imaging; NF1, neurofibromatosis type 1. * At the time of diagnosis in an infant (1 month to 1 year). **Indicates to be performed in infants and children (1 year to adolescent). ***Advise for more frequent visits as indicated in children (5 years to adolescent). ^#At least once in this time period in children (5 years to adolescent).

Figure 3

Overview of surveillance for tumor screening and recommendations for their management. Adapted from Carton et al., 2023 (75). CT, computed tomography; ¹⁸FDG PET MRI, ¹⁸F-fluorodeoxyglucose positron emission tomography magnetic resonance imaging; ¹⁸FDG PET-CT, ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography; MEK, mitogen-activated protein kinase; MPNST, Malignant peripheral nerve sheath tumor; MRI, magnetic resonance imaging; mTOR, mammalian target of rapamycin; NF1, neurofibromatosis type 1; OCT, optic coherence tomography; PN, plexiform neurofibromas. *For high-grade gliomas, a detailed family history and genetic testing (whole exome sequencing) need to be taken if not already done.

Figure 4

Management algorithm for NF1 associated with neurofibromas. NF1, neurofibromatosis type 1. *Treatment modality for unresectable plexiform neurofibroma and refractory tumor. Chemotherapy includes agents such as carboplatin-based therapy. Targeted therapy includes mitogen-activated protein kinase and mammalian target of rapamycin and MEK inhibitors.

Figure 5

Proposed referral algorithm for patients with NF1. *All asymptomatic patients should be referred to an ophthalmologist. ADD, attention-deficit disorder; ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; NF1, neurofibromatosis type 1; NIH, National Institutes of Health.

Figure 6

Overview of eligibility criteria for setting NF1 center of excellence. MDT, multidisciplinary team; MPNST, Malignant peripheral nerve sheath tumor; MRI, magnetic resonance imaging; NF1, neurofibromatosis type 1; PET, positron emission tomography.