Case report of neurofibromatosis type 1 combined with primary ciliary dyskinesia

Abstract

Neurofibromatosis (NF) is a genetic disease in which the lungs are rarely involved. However, in NF cases with lung involvement, chest computed tomography may show bilateral basal reticulations, apical bullae, and cysts without bronchiectasis. Herein, we report a patient diagnosed with NF on the basis of the results of genetic testing who presented with early-onset wet cough and bronchiectasis. Considering the differential diagnosis of bronchiectasis combined with his early-onset wet cough, sinusitis, and sperm quality decline, we considered the possibility of primary ciliary dyskinesia (PCD). Further electron microscopy analysis of cilia and identification of homozygous mutations in the RSPH4A gene confirmed the diagnosis of PCD. Therefore, for patients with NF, when an image change exists in the lungs that does not correspond to NF, the possibility of other diagnoses, including PCD, must be considered.

Keywords

primary ciliary dyskinesia / neurofibromatosis / bronchiectasis / transmission electron microscopy / genetic sequencing

References

[1] Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ. Neurofibromatosis type 1. Nat Rev Dis Primers 2017; 3(1): 17004

[2] Alves Júnior SF, Zanetti G, Alves de Melo AS, Souza AS Jr, Souza LS, de Souza Portes Meirelles G, Irion KL, Hochhegger B, Marchiori E. Neurofibromatosis type 1: state-of-the-art review with emphasis on pulmonary involvement. Respir Med 2019; 149: 9–15

[3] Cimino PJ, Gutmann DH. Neurofibromatosis type 1. Handb Clin Neurol 2018; 148: 799–811

[4] Zamora AC, Collard HR, Wolters PJ, Webb WR, King TE. Neurofibromatosis-associated lung disease: a case series and literature review. Eur Respir J 2007; 29(1): 210–214

[5] Mirra V, Werner C, Santamaria F. Primary ciliary dyskinesia: an update on clinical aspects, genetics, diagnosis, and future treatment strategies. Front Pediatr 2017; 5: 135

[6] Frommer A, Hjeij R, Loges NT, Edelbusch C, Jahnke C, Raidt J, Werner C, Wallmeier J, Große-Onnebrink J, Olbrich H, Cindrić S, Jaspers M, Boon M, Memari Y, Durbin R, Kolb-Kokocinski A, Sauer S, Marthin JK, Nielsen KG, Amirav I, Elias N, Kerem E, Shoseyov D, Haeffner K, Omran H. Immunofluorescence analysis and diagnosis of primary ciliary dyskinesia with radial spoke defects. Am J Respir Cell Mol Biol 2015; 53(4): 563–573

[7] Horani A, Ferkol TW. Advances in the genetics of primary ciliary dyskinesia: clinical implications. Chest 2018; 154(3): 645–652

[8] Knowles MR, Zariwala M, Leigh M. Primary ciliary dyskinesia. Clin Chest Med 2016; 37(3): 449–461

[9] Zariwala MAKM, Leigh MW. Primary Ciliary Dyskinesia. 2007 Jan 24 [Updated 2019 Dec 5]. In: Adam MP, Ardinger HH, Pagon RA, et al. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle. 1993–2021

[10] Lionetti E, Francavilla R, Ruggieri M, Di Stefano V, Principi MB, Pavone L. Recurrent peptic ulcer disease in a pediatric patient with type 1 neurofibromatosis and primary ciliary dyskinesia. Minerva Pediatr 2009; 61(5): 557–559

[11] Castleman VH, Romio L, Chodhari R, Hirst RA, de Castro SC, Parker KA, Ybot-Gonzalez P, Emes RD, Wilson SW, Wallis C, Johnson CA, Herrera RJ, Rutman A, Dixon M, Shoemark A, Bush A, Hogg C, Gardiner RM, Reish O, Greene ND, O’Callaghan C, Purton S, Chung EM, Mitchison HM. Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities. Am J Hum Genet 2009; 84(2): 197–209

[12] Daniels ML, Leigh MW, Davis SD, Armstrong MC, Carson JL, Hazucha M, Dell SD, Eriksson M, Collins FS, Knowles MR, Zariwala MA. Founder mutation in RSPH4A identified in patients of Hispanic descent with primary ciliary dyskinesia. Hum Mutat 2013; 34(10): 1352–1356

[13] Roth J, Constantini S, Cinalli G.Neurofibromatosis type 1-related hydrocephalus: causes and treatment considerations. Childs Nerv Syst 2020; 36(10): 2385–2390PMID: 32504175 2020.

Conclusions

In this case, an extremely rare case of combined PCD and NF1 was described. Although the diagnosis of NF was clear, lung changes inconsistent with NF led us to consider the differential diagnosis of bronchiectasis. Finally, the diagnosis of PCD combined with NF was made by observing relevant clinical manifestations, transmission electron microscopy changes, and related gene (i.e., RSPH4A) mutations.

Acknowledgements

This research was supported by the National Key Research and Development Program of China (No. 2016YFC0901502) and CAMS Innovation Fund for Medical Sciences (Nos. CIFMS-2018-I2M-1-003, CIFMS-2017-12M-2-001, CIFMS-2020-I2M-C&T-B-002, and CIFMS-2016-I2M-1-002).

Compliance with ethics guidelines

Chun Bian, Xinyue Zhao, Yaping Liu, Minjiang Chen, Shuying Zheng, Xinlun Tian, and Kai-Feng Xu declare that they have no conflict of interest. Informed consent was obtained from the patient for publication of all related materials.

RIGHTS & PERMISSIONS

2021 Higher Education Press