An inherited condition that is rather frequent is neurofibromatosis type 1, a subtype of neurofibromatosis (NF). Patients are more susceptible to both benign and malignant tumor development in NF. Although the nervous system is impacted by various neurofibromatosis type 1 symptoms, other organs and tissues may also be affected. Patients may visit various medical and surgical specialists due to the disorder's variable characteristics and clinical heterogeneity, making it difficult to recognize the connection between the clinical symptoms and neurofibromatosis type 1. Therefore, clinicians must be familiar with the variety of clinical symptoms of this illness to make an accurate diagnosis and provide the best therapy for patients with neurofibromatosis type 1.
Multi-organ involvement in NF
Apart from the brain, spinal cord, skin, and nerves, many other organ systems are affected in neurofibromatosis type 1, which include:
Skeletal system : Anomalies include osteopenia, scoliosis, sphenoid wing dysplasia, congenital tibial dysplasia, and pseudarthrosis. Additionally, affected people generally have poor bone-mineral densities and are typically shorter than would be expected for their age.
Gastrointestinal system : These tumors are of mesenchymal origin and can grow anywhere along the gastrointestinal tract. Symptoms are abdominal pain, bleeding, intestinal perforation, and blockage are the most often reported symptoms. They may be discovered accidentally during imaging tests, discovered accidentally after surgery to remove another tumor, or discovered through the patient's symptoms.
Breast cancer : Neurofibromatosis type 1 has been linked to a fivefold increased risk for breast cancer, primarily affecting women under 50. Additionally, mortality rates for women with breast cancer and neurofibromatosis type 1 are greater than those for women with breast cancer in the general population.
Cardiovascular system : congenital heart disease, vasculopathy, and hypertension are seen.
Others : lymphomas, leukemias, phaeochromocytoma, duodenal carcinoids, and rhabdomyosarcoma[1].
A brief view on cardiac manifestations in NF
The NF1 gene is located on chromosome 17 and encodes the protein neurofibromin, which controls cell growth by preventing epidermal growth factor receptor activation. This neurofibromin has been found in the aorta's smooth muscle layer. Experimental investigations show that in the absence of this protein, the heart hyper proliferates and lacks appropriate functioning. These findings imply that the cardiovascular system is involved in NF1.
Congenital heart disease, vasculopathy, and hypertension are just a few of the cardiovascular problems that patients with neurofibromatosis type 1 might have. According to echocardiographic evidence, pulmonary artery stenosis may be the cause of up to 50% of the cardiovascular problems found in patients with neurofibromatosis type 1 (up to 27% of patients). Because abnormalities are typically only diagnosed after symptoms manifest, the prevalence of abnormalities is probably underestimated. All newborns with neurofibromatosis type 1 should therefore undergo a comprehensive heart examination, and any murmurs should be further explored by a qualified pediatric cardiologist[2].
Aortic coarctation, renal and cerebral artery stenosis and arteriovenous malformations are among the vasculopathies associated with neurofibromatosis type 1. Although the pathophysiology, clinical range, and natural history of these anomalies are still poorly understood, vascular endothelial cells with defective NF1 gene function proliferate and develop more quickly. Vasculopathy typically affects the arterial system, resulting in renal artery stenosis or cerebrovascular disease (such as congested or ectatic arteries, vascular stenosis, or aneurysm).
When a new neurological defect manifests in a patient with neurofibromatosis type 1, both cerebrovascular illness and brain tumor should be ruled out. Additionally, every patient with unexplained hypertension should be checked for any renal artery stenosis. It is crucial to perform the necessary imaging investigations, arteriography, and laboratory evaluations (including urinalysis, plasma renin, serum creatinine, and electrolytes), even with persistent essential hypertension.
The coarctation of the aorta and pheochromocytoma are the two other causes of elevated blood pressure in this population, however, essential hypertension still accounts for the majority of cases. Although it's unknown if vascular stenosis is genuinely present at birth, some of these anomalies are probably congenital. To clear up these doubts, more research is required[3].
Scope of treatment of cardiac problems in NF
For every 2 years, repeated follow-up cardiac examinations should be conducted which include an examination, an electrocardiogram, and ambulatory electrocardiographic monitoring. Renal artery angioplasty is the treatment of choice for aortic stenosis, but individuals with NF1 reported to have a poor success rate with renal artery angioplasty than patients without NF1. In these individuals, surgical revascularization or nephrectomy frequently lowers blood pressure; however, nephrectomy should only be performed in cases of parenchymal lesions or severe renal artery disease. Given that essential hypertension cannot be accurately detected on a prospective basis, the high incidence of essential hypertension among NF1 patients likely contributes to surgical treatment failures. If a congenital heart disease is discovered, the patient's age, the kind, and the degree of the lesion should all be taken into consideration when determining the next steps in follow-up and therapy[4].
Do your part, care for your heart
Identification of NF patients accurately and giving them prompt treatment as well as monitoring the suspected NF patients at regular intervals and arriving at early diagnosis will help in the remission of the symptoms and limitation of the disease without the involvement of multiple organs. Even if cardiac involvement occurs it can be minimized with early and prompt treatment.
References
A. C. Hirbe and D. H. Gutmann, “Neurofibromatosis type 1: a multidisciplinary approach to care,” Lancet Neurol, vol. 13, no. 8, pp. 834–843, Aug. 2014, doi: 10.1016/S1474-4422(14)70063-8.
A. E. Lin et al., “Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1,” Am J Med Genet, vol. 95, no. 2, pp. 108–117, Nov. 2000, doi: 10.1002/1096-8628(20001113)95:2<108::aid-ajmg4>3.0.co;2-0.
G. S. Oderich et al., “Vascular abnormalities in patients with neurofibromatosis syndrome type I: clinical spectrum, management, and results,” J Vasc Surg, vol. 46, no. 3, pp. 475–484, Sep. 2007, doi: 10.1016/j.jvs.2007.03.055.
J. M. Friedman et al., “Cardiovascular disease in neurofibromatosis 1: Report of the NF1 Cardiovascular Task Force,” Genet Med, vol. 4, no. 3, Art. no. 3, May 2002, doi: 10.1097/00125817-200205000-00002.
