Dados do Trabalho

Título

NEUROFIBROMATOSIS-NOONAN SYNDROME: CLINICAL AND GENETIC ASPECTS

Apresentação do caso único

Male patient, 5 years old, Caucasian, born full-term to non-consanguineous parents. He had bilateral cryptorchidism, pectus carinatum, and significant delays in speech development despite good comprehension. During bronchiolitis hospitalization, echocardiography found congenital heart defects. Physical exam revealed facial dysmorphisms and café-au-lait spots. Genetic testing confirmed NFNS with NF1 gene variant (c.2375T>A p.(Leu792His)).

Discussão

Neurofibromatosis-Noonan Syndrome (NFNS) is characterized by a blend of Neurofibromatosis Type 1 (NF1) and Noonan syndrome features, stemming from mutations in the RAS-MAPK pathway. NF1, or Von Recklinghausen disease, is an autosomal dominant neurocutaneous disorder with café-au-lait spots, neurofibromas, Lisch nodules, and systemic involvement due to NF1 gene haploinsufficiency on chromosome 17q11.2. Neurofibromin, its protein product, regulates cell proliferation in various tissues, predisposing to tumor formation. Therapeutic strategies focus on tumor suppression and include laser therapy. Noonan syndrome, characterized by facial dysmorphisms, congenital heart disease, and short stature, is caused by mutations in RAS/MAPK pathway genes like PTPN11, impacting cellular growth and differentiation. NFNS, sharing pathophysiological mechanisms and clinical features with NF1 and Noonan syndrome, manifests variably due to mutations in genes like PTPN11 and NF1, influencing clinical presentation. Studies highlight genotype-phenotype correlations revealing symptoms such as short stature, learning difficulties, café-au-lait spots, and cardiac anomalies related to NF1 mutations.

Comentários finais

This case highlights the intricate clinical and genetic diversity of Neurofibromatosis-Noonan Syndrome, underscoring the need for continuous research and patient monitoring despite subtle symptoms. Diagnosis poses challenges and typically involves genetic testing but can also be considered based on clinical signs alone. This report aims to enhance understanding of the syndrome, supporting early detection through clinical features and advocating for multidisciplinary care and innovative treatment approaches.

Referências

1. Nyström, A. M., Ekvall, S., Allanson, J., Edeby, C., Elinder, M., Holmström, G., Bondeson, M. L., & Annerén, G. (2009). Noonan syndrome and neurofibromatosis type I in a family with a novel mutation in NF1. Clinical Genetics, 76(6), 524-534. https://doi.org/10.1111/j.1399-0004.2009.01233.x

2. Falahat, B., & Khosravi, M. (2023). Neurofibromatosis-Noonan syndrome and growth deficiency in an Iranian girl due to a pathogenic variant in the NF1 gene. American Journal of Medical Genetics Part A, 191(10), 2389-2395. https://doi.org/10.1002/ajmg.a.36313

3. Saleh, M., Dib, A., Beaini, S., Saad, C., Faraj, S., El Joueid, Y., Kotob, Y., Saoudi, L., & Emmanuel, N. (2023). Neurofibromatosis type 1 system-based manifestations and treatments: A review. Journal of Neurology, 270(7), 3081-3090. https://doi.org/10.1007/s10072-023-06680-5

4. Trovo-Marqui AB, Tajara EH. Neurofibromin: an overview. Clin Genet 2006: 70: 1-13.

5. Ullrich, N. J., Prabhu, S. P., Reddy, A. T., et al. (2020). A phase II study of the oral continuous mTOR inhibitor everolimus for progressive recurrent radiographic low-grade pediatric glioma associated with neurofibromatosis type 1: A neurofibromatosis clinical trials consortium study. Neuro-Oncology, 22(10), 1527–1535. https://doi.org/10.1093/neuonc/noaa071

6. Carcavilla, A., Suárez-Ortega, L., Rodríguez Sánchez, A., Gonzalez-Casado, I., Ramón-Krauel, M., Labarta, J. I., Quinteiro Gonzalez, S., Riaño Galán, I., Ezquieta Zubicaray, B., & López-Siguero, J. P. (2020). Noonan syndrome: Genetic, clinical, and therapeutic updates. Anales de Pediatría, 93(1), 61.e1-61.e14. https://doi.org/10.1016/j.anpedi.2020.04.008

7. Roberts AE, Allanson JE, Tartaglia M, et al. Noonan syndrome. Lancet 2013; 381: 333-42. doi:10.1016/S0140-6736(12)61023-X http://www.ncbi.nlm.nih.gov/pubmed/23312968

8. Perrino F, Licchelli S, Serra G, et al. Psychopathological features in Noonan syndrome. Eur J Paediatr Neurol 2018; 22: 170-7. doi:10.1016/j.ejpn.2017.09.009 http://www.ncbi.nlm.nih.gov/pubmed/29037749

9. Mohapatra I, Samantaray SR (July 18, 2023) Neurofibromatosis-Noonan Syndrome With Primary Amenorrhoea: A Case Report. Cureus 15(7): e42098. doi:10.7759/cureus.42098

10. Kehrer-Sawatzki H, Mautner VF, Cooper DN. Emerging genotype-phenotype relationships in patients with large deletions of NF1. Hum Genet. 2017;136(4):349-76.

Palavras Chave

Neurofibromatosis-Noonan Syndrome (NFNS); Neurofibromatosis Type 1 (NF1); Noonan syndrome (NS)