Is neurofibromatosis type 1 diagnosed in every patient who presents with café au lait macules? A single-center experience

Year 2023, Volume: 36 Issue: 2, 192 - 196, 31.05.2023

Nursah Eker Ayse Gulnur Tokuc Burcu Tas Tufan Emel Senay

https://doi.org/10.5472/marumj.1302264

Abstract

Objective: Neurofibromatosis type 1 (NF1) is the most common hereditary neurocutaneous syndrome. The most crucial morbidity of
NF1 is tumors that may develop. Cases with café-au-lait macules (CALMs) which is the first clinical finding of NF1, due to the anxiety
of its associated morbidity, are referred to the pediatric oncology clinic. In this study, we aimed to examine the characteristics of the
patients who applied to our outpatient clinic with CALMs.
Patients and Methods: The data of 157 pediatric patients who applied to our institution with the diagnosis of CALMs between June
2010 and November 2020 were analyzed retrospectively.
Results: There were 157 pediatric cases referred to us for CALMs. According to the National Institutes of Health (NIH) diagnostic
criteria, 109 (69.4%) cases were diagnosed with NF1. The diagnosis of 22 cases with NF1 were supported by genetic examination.
Optic glioma was detected in 39 (24.8%) cases. In 15 (38.4%) of cases with optic glioma, visual functions were also affected. Second
diagnostic criterion did not develop during the follow-up period, except for macules, in 48 cases (30.5%).
Conclusion: In cases with multiple CALMs, the probability of NF1 diagnosis is high, and close and regular follow-up is of great
importance in catching the development of the second clinical criterion and minimizing its morbidity.

Keywords

Café-au-lait macule, Neurofibromatosis, Children, Tumor

References

• [1] Alper JC, Holmes LB. The incidence and significance of birthmarks in a cohort of 4,641 newborns. Pediatr Dermatol 1983;1:58-68. doi: 10.1111/j.1525-1470. 1983. tb01093.x
• [2] Whitehouse D. Diagnostic value of the cafe-au-lait spot in children. Arch Dis Child 1966; 41:316-9. doi: 10.1136/ adc.41.217.316
• [3] Friedman J M, Gutmann D H, MacCollin M, et al. Neurofibromatosis: phenotype,natural history, and pathogenesis . 3. Edition. Baltimore: Johns Hopkins University Press, 1999.
• [4] Rosenbaum T, Wimmer K. Neurofibromatosis Type 1 and associated tumors. Klin Paditr 2014; 226: 309-15 doi: 10.1055/ s-0034.138.2021
• [5] Ferner RE, Huson SM, Thomas N, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet 2007; 44: 81-8. doi: 10.1136/ jmg.2006.045906
• [6] National Institutes of Health Consensus Development Conference Statement: neurofibromatosis-Bethesda, MD, USA, July 13-15, 1987. Neurofibromatosis 1988; 1: 172-8.
• [7] Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a multidisciplinary approach to care. Lancet Neurol 2014; 13: 834-43. doi: 10.1016/S1474-4422(14)70063-8
• [8] Nunley KS, Gao F, Albers AC, Bayliss SJ, Gutmann DH. Predictive value of cafe au lait macules at initial consultation in the diagnosis of neurofibromatosis type 1. Arch Dermatol 2009; 145:883-7. doi: 10.1001/archdermatol.2009.169
• [9] Kim MJ, Cheon CK. Neurofibromatosis type 1: a single center’s experience in Korea. Korean J Pediatr 2014;57:410-5. doi: 10.3345/kjp.2014.57.9.410
• [10] Sevick RJ, Barkovich AJ, Edwards MSB, et al. Evolution of whitematter lesions in neurofibromatosis type 1: MR findings. AJR Am J Roentgenol 1992; 159: 171-5. doi: 10.2214/ ajr.159.1.1609692
• [11] Yao R, Wang L, Yu Y, Wang J, Shen Y. Diagnostic value of multiple cafe-au-lait macules for neurofibromatosis 1 in Chinese children. J Dermatol 2016; 43: 537-42. doi: 10.1111/1346-8138.13169
• [12] Falzon K, Drimtzias E, Picton S, Simmons I. Visual outcomes after chemotherapy for optic pathway glioma in children with or without neurofibromatosis type 1: results of the International Society of Paediatric Oncology (SIOP) Low- Grade Glioma 2004 trial UK cohort. Br J Ophthalmol 2018; 102: 1367-71. doi: 10.1136/bjophthalmol-2017-311305
• [13] Akbarnia BA, Gabriel KR, Beckman E, Chalk D. Prevalence of scoliosis in neurofi bromatosis. Spine 1992; 17: 244-48. doi: 10.1097/00007.632.199208001-00005
• [14] Kaçar AG, Oktay B, Özel S, et al. Neurofibromatosis type 1 in children: A single-center experience. Turk Arch Pediatr 2021; 56: 339-43. doi: 10.5152/TurkArchPediatr. 2021.20165
• [15] Cnossen MH, Stam EN, Cooiman LC, et al. Endocrinologic disordersand optic pathway gliomas in children with neurofibromatosis type 1. Pediatrics 1997; 100:667-70. doi: 10.1542/peds.100.4.667
• [16] Bruzzi P, Sani I, Albanese A. Reversible growth hormone excess in two girls with neurofibromatosis type 1 and optic pathway glioma. Horm Res Paediatr 2015; 84:414-422. doi: 10.1159/000440956
• [17] Sani I, Albanese A. Endocrine long-term follow-up of children with neurofibromatosis type 1 and optic pathway glioma. Horm Res Paediatr 2017; 87:179-88. doi: 10.1159/000458525
• [18] Santoro C, Perrotta S, Picariello S, et al. Pretreatment endocrine disorders due to optic pathway gliomas in pediatric neurofibromatosis type 1: Multicenter study. J Clin Endocrinol Metab 2020; 105: dgaa138. doi: 10.1210/clinem/dgaa138
• [19] Lin AE, Birch PH, Korf BR, et al. Cardiovascular malformations and other cardiovascular abnormalities in neurofibromatosis 1. Am J Med Genet 2000; 95:108-17. doi: 10.1002/1096- 8628(20001113)95:2<108 aid-ajmg4>3.0.co;2-0
• [20] Lama G, Graziano L, Calabrese E, et al. Blood pressure and cardiovascular involvement in children with neurofibromatosis type1. Pediatr Nephrol 2004; 19:413-8. doi: 10.1007/s00467.003.1397-5
• [21] İncecik F, Hergüner ÖM, Erdem SA, Altunbaşak Ş. Neurofibromatosis type 1 and cardiac manifestations. Turk Kardiyol Dern Ars 2015; 43: 714-6. doi: 10.5543/ tkda.2015.27557