Abordaje clínico de variantes fenotípicas en neurofibromatosis de tipo 1
Palabras clave:
neurofibromatosis 1, neurofibromina, mutación, agenesia, diagnóstico y consejería genéticaResumen
La neurofibromatosis de tipo 1 es una enfermedad genética de herencia autosómica dominante, de afectación multisistémica y gran variabilidad fenotípica, causada por una mutación del gen NF1 localizada en el cromosoma 17 q11.2 que afecta la codificación de la neurofibromina.
La prevalencia mundial se estima en 1 de cada 4.000 a 5.000 individuos. En Colombia se desconoce su prevalencia. Los criterios diagnósticos establecidos por los National Institutes of Health incrementaron la sensibilidad diagnóstica para pacientes con neurofibromatosis de tipo 1, quienes presentan manifestaciones clínicas cutáneas y extracutáneas, para las cuales se propone una clasificación en siete grupos, según el sistema u órgano afectado, y en tres tipos de variantes clínicas: tumores, alteraciones esqueléticas y alteraciones oftalmológicas. Se describe la disponibilidad de pruebas diagnósticas y asesoría genética.
Biografía del autor/a
Dora Lucía Vallejo
Laboratorio de Genética Humana, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga. Colombia.
Jairo Enrique López
Laboratorio de Genética Humana, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga. Colombia.
Referencias bibliográficas
1. Tonsgard JH. Clinical manifestations and management of neurofibromatosis type 1. Semin Pediatr Neurol. 2006;13:2-7.
2. Cawthon RM, Weiss R, Xu G, Viskochil D, Culver M, Stevens J, et al. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990;62:193-201.
3. Yohay KH. The genetic and molecular pathogenesis of NF1 and NF2. Semin Pediatr Neurol. 2006;13:21-6.
4. Li Y, O’Connell P, Breidenbach HH, Cawthon R, Stevens J, Xu G, et al. Genomic organization of the neurofibromatosis 1 gene (NF1). Genomics. 1995;25:9-18.
5. Fang LJ, Simard MJ, Vidaud D, Assouline B, Lemieux B, Vidaud M, et al. A novel mutation in the neurofibromatosis type 1 (NF1) gene promotes skipping of two exons by preventing exon definition. J Mol Biol. 2001;307:1261-70.
6. Ferner RE. Neurofibromatosis 1. Eur J Hum Genet. 2007;15:131-8.
7. North KN. Neurofibromatosis 1 in childhood. Semin Pediatr Neurol. 1998;5:231-42.
8. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44:81-8.
9. North KN. Clinical aspects of neurofibromatosis 1. Eur J Paediatr Neurol. 1998;2:223-31.
10. Sørensen SA, Mulvihill JJ, Nielsen A. Long-term follow-up of von Recklinghausen neurofibromatosis. N Engl J Med. 1986;314:1010-5.
11. Friedman JM. Epidemiology of neurofibromatosis type 1. Am J Med Genet (Sem Med Genet) 1999;89:1-6.
12. Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL. Neurofibromatosis type 1 revisited. Pediatrics. 2009;123:124-33.
13. Zhu H, Hinman MN, Hasman RA, Mehta P, Lou H. Regulation of neuron-specific alternative splicing of neurofibromatosis type 1 pre-mRNA. Mol Cell Biol. 2008;28:1240-51.
14. Yang FC, Chen S, Robling AG, Yu X, Nebesio TD, Yan J, et al. Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions. J Clin Invest. 2006;116:2880-91.
15. Shen MH, Harper PS, Upadhyaya M. Molecular genetics of neurofibromatosis type 1 (NF1). J Med Genet. 1996;33:2-17.
16. von Deimling A, Krone W, Menon AG. Neurofibromatosis type 1: Pathology, clinical features and molecular genetics. Brain Pathol. 1995;5:153-62.
17. Levy P, Bieche I, Leroy K, Parfait B, Wechsler J, Laurendeau I, et al. Molecular profiles of neurofibromatosis type 1-associated plexiform neurofibromas: Identification of a gene expression signature of poor prognosis. Clin Cancer Res. 2004;10:3763-71.
18. Mulvihill JJ. Neurofibromatosis. Ann NY Acad Sci. 1986;486:38-44.
19. Riccardi VM, Lewis RA. Penetrance of von Recklinghausen neurofibromatosis: A distinction between predecessors and descendants. Am J Hum Genet. 1988;42:284-9.
20. Boyd KP, Gao L, Feng R, Beasley M, Messiaen L, Korf BR, et al. Phenotypic variability among café-au-lait macules in neurofibromatosis type 1. J Am Acad Dermatol. 2010;63:440-7.
21. Knudson AG, Jr. Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971;68:820-3.
22. Lee MJ, Stephenson DA. Recent developments in neurofibromatosis type 1. Curr Opin Neurol. 2007;20:135-41.
23. Carey JC, Viskochil DH. Neurofibromatosis type 1: A model condition for the study of the molecular basis of variable expressivity in human disorders. Am J Med Genet. 1999;89:7-13.
24. Eichenfield LF, Levy ML, Paller AS, Riccardi VM. Guidelines of care for neurofibromatosis type 1. J Am Acad Dermatol. 1997;37:625-30.
25. Diwakar G, Hornyak TJ. Cafe-au-lait patches and senile plaques: How APPt the connection? J Invest Dermatol. 2006;126:547-50.
26. Boyd KP, Korf BR, Theos A. Neurofibromatosis type 1. J Am Acad Dermatol. 2009;61:1-14.
27. Ilyas AM, Nourissat G, Jupiter JB. Segmental neurofibromatosis of the hand and upper extremity: A case report. J Hand Surg. 2007;32:1538-42.
28. Raygada M, Arthur DC, Wayne AS, Rennert OM, Toretsky JA, Stratakis CA. Juvenile xanthogranuloma in a child with previously unsuspected neurofibromatosis type 1 and juvenile myelomonocytic leukemia. Pediatr Blood Cancer. 2010;54:173-5.
29. Orozco J, Besson A, Pulido M, Ruiz J, Linares E, Sáez MR. Neurofibromatosis tipo 1 (NF1) revisión y presentación de un caso clínico con manifestaciones bucofaciales. Avances en Odontoestomatología. 2005;21:231-9.
30. Holt GR. ENT manifestations of von Recklinghausen’s disease. Laryngoscope. 1978;88:1617-32.
31. Friedman JM, Birch PH. Type 1 neurofibromatosis: A descriptive analysis of the disorder in 1.728 patients. Am J Med Genet. 1997;70:138-43.
32. Kissil JL, Blakeley JO, Ferner RE, Huson SM, Kalamarides M, Mautner VF, et al. What’s new in neurofibromatosis? Am J Med Genet A. 2010;152A:269-83.
33. Mumoli N, Cei M, Bartolomei C, Pirillo V. A patient with loss of vision in the right eye and neurofibromatosis type 1. CMAJ. 2009;180:203-6.
34. Hope DG, Mulvihill JJ. Malignancy in neurofibromatosis. Adv Neurol. 1981;29:33-56.
35. Topsakal C, Akdemir I, Tiftikci M, Ozercan I, Aydin Y. Malignant schwannoma of the sciatic nerve originating in a spinal plexiform neurofibroma associated with neurofibromatosis type 1 -case report. Neurol Med Chir (Tokyo). 2001;41:551-5.
36. Friedrich RE, Mautner VF, Scheuer HA. Loss of heterozygosity in tumor cells of a recurrent mandibular giant cell granuloma in neurofibromatosis type 1. Anticancer Res. 2007;27:2079-83.
37. Hefti F, Bollini G, Dungl P, Fixsen J, Grill F, Ippolito E, et al. Congenital pseudarthrosis of the tibia: History, etiology, classification, and epidemiologic data. J Pediatr Orthop B. 2000;9:11-5.
38. Crawford A, Schorry E. Neurofibromatosis in children: The role of the orthopaedist. J Am Acad Orthop Surg. 1999;7:217-30.
39. Vallejo D, Lopéz J, Contreras G.Neurofibromatosis tipo 1, agenesia de peroné bilateral con acortamiento de tibia en forma triangular y mutación en el exón 24 p. K 1423E: reporte de caso y revisión de la literatura. IATREIA. 2010;23:s110.
40. McFarland B. Pseudarthrosis of the tibia in childhood. J Bone Joint Surg Br. 1951;33:36-46.
41. Cheema JI, Grissom LE, Harcke HT. Radiographic characteristics of lower-extremity bowing in children. Radiographics. 2003;23:871-80.
42. Tuncay IC, Johnston CE, 2nd, Birch JG. Spontaneous resolution of congenital anterolateral bowing of the tibia. J Pediatr Orthop. 1994;14:599-602.
43. Karol LA, Haideri NF, Halliday SE, Smitherman TB, Johnston CE, 2nd. Gait analysis and muscle strength in children with congenital pseudarthrosis of the tibia: The effect of treatment. J Pediatr Orthop. 1998;18:381-6.
44. Fixsen JA. Major congenital shortening of the lower limb and congenital pseudarthrosis of the tibia. J Pediatr Orthop B. 1995;4:142-4.
45. Lehman WB, Abdelgawad AA, Sala DA. Congenital tibial dysplasia (congenital pseudoarthrosis of the tibia): An atypical variation. J Pediatr Orthop B. 2009;18:211-3.
46. Boyd HB. Pathology and natural history of congenital pseudarthrosis of the tibia. Clin Orthop Relat Res. 1982;166:5-13.
47. Traub JA, O’Connor W, Masso PD. Congenital pseudarthrosis of the tibia: A retrospective review. J Pediatr Orthop. 1999;19:735-8.
48. Grill F, Bollini G, Dungl P, Fixsen J, Hefti F, Ippolito E, et al. Treatment approaches for congenital pseudarthrosis of tibia: Results of the EPOS multicenter study. J Pediatr Orthop B. 2000;9:75-89.
49. Erni D, De Kerviler S, Hertel R, Slongo T. Vascularised fibula grafts for early tibia reconstruction in infants with congenital pseudarthrosis. J Plast Reconstr Aesthet Surg. 2010;63:1699-704.
50. Akbarnia BA, Gabriel KR, Beckman E, Chalk D. Prevalence of scoliosis in neurofibromatosis. Spine. 1992;17(Suppl.8):S244-8.
51. Pérez LM, Marrero LO, Rochè HE, Calzado R, González C. Diagnóstico clinicoimagenológico de la neurofibromatosis tipo 1. Revista Cubana de Ortopedia y Traumatología. 2005;19 (1):47-50.
52. Mahnken AH, Staatz G, Hermanns B, Gunther RW, Weber M. Congenital pseudarthrosis of the tibia in pediatric patients: MR imaging. Am J Roentgenol. 2001;177:1025-9.
53. Lovell AT, Alexander R, Grundy EM. Silent, unstable, cervical spine injury in multiple neurofibromatosis. Anaesthesia. 1994;49:453-4.
54. Rocchietti M, De Palma C, L’Angiocola PD, Aliberti G. Neurofibromatosis type I and hypertension: A case report. Recenti Prog Med. 2008;99:602-5.
55. Prave F, Hach-Wunderle V, Hach W. Vascular manifestation of von Recklinghausen neurofibromatosis: Case report of venous dysplasia. Vasa. 2003;32:36-9.
56. Virdis R, Sigorini M, Laiolo A, Lorenzetti E, Street ME, Villani AR, et al. Neurofibromatosis type 1 and precocious puberty. J Pediatr Endocrinol Metab. 2000;13(Suppl.1):841-4.
57. Zografos GN, Vasiliadis GK, Zagouri F, Aggeli C, Korkolis D, Vogiaki S, et al. Pheochromocytoma associated with neurofibromatosis type 1: Concepts and current trends. World J Surg Oncol. 2010;8:14.
58. Yantiss RK, Rosenberg AE, Sarran L, Besmer P, Antonescu CR. Multiple gastrointestinal stromal tumors in type I neurofibromatosis: A pathologic and molecular study. Mod Pathol. 2005;18:475-84.
59. North K. Neurofibromatosis type 1. Am J Med Genet. 2000;97:119-27.
60. Hyman SL, Shores A, North KN. The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology. 2005;65:1037-44.
61. North K, Joy P, Yuille D, Cocks N, Mobbs E, Hutchins P, et al. Specific learning disability in children with neurofibromatosis type 1: Significance of MRI abnormalities. Neurology. 1994;44:878-83.
62. Maertens O, De Schepper S, Vandesompele J, Brems H, Heyns I, Janssens S, et al. Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1. Am J Hum Genet. 2007;81:243-51.
2. Cawthon RM, Weiss R, Xu G, Viskochil D, Culver M, Stevens J, et al. A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations. Cell. 1990;62:193-201.
3. Yohay KH. The genetic and molecular pathogenesis of NF1 and NF2. Semin Pediatr Neurol. 2006;13:21-6.
4. Li Y, O’Connell P, Breidenbach HH, Cawthon R, Stevens J, Xu G, et al. Genomic organization of the neurofibromatosis 1 gene (NF1). Genomics. 1995;25:9-18.
5. Fang LJ, Simard MJ, Vidaud D, Assouline B, Lemieux B, Vidaud M, et al. A novel mutation in the neurofibromatosis type 1 (NF1) gene promotes skipping of two exons by preventing exon definition. J Mol Biol. 2001;307:1261-70.
6. Ferner RE. Neurofibromatosis 1. Eur J Hum Genet. 2007;15:131-8.
7. North KN. Neurofibromatosis 1 in childhood. Semin Pediatr Neurol. 1998;5:231-42.
8. Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, et al. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. J Med Genet. 2007;44:81-8.
9. North KN. Clinical aspects of neurofibromatosis 1. Eur J Paediatr Neurol. 1998;2:223-31.
10. Sørensen SA, Mulvihill JJ, Nielsen A. Long-term follow-up of von Recklinghausen neurofibromatosis. N Engl J Med. 1986;314:1010-5.
11. Friedman JM. Epidemiology of neurofibromatosis type 1. Am J Med Genet (Sem Med Genet) 1999;89:1-6.
12. Williams VC, Lucas J, Babcock MA, Gutmann DH, Korf B, Maria BL. Neurofibromatosis type 1 revisited. Pediatrics. 2009;123:124-33.
13. Zhu H, Hinman MN, Hasman RA, Mehta P, Lou H. Regulation of neuron-specific alternative splicing of neurofibromatosis type 1 pre-mRNA. Mol Cell Biol. 2008;28:1240-51.
14. Yang FC, Chen S, Robling AG, Yu X, Nebesio TD, Yan J, et al. Hyperactivation of p21ras and PI3K cooperate to alter murine and human neurofibromatosis type 1-haploinsufficient osteoclast functions. J Clin Invest. 2006;116:2880-91.
15. Shen MH, Harper PS, Upadhyaya M. Molecular genetics of neurofibromatosis type 1 (NF1). J Med Genet. 1996;33:2-17.
16. von Deimling A, Krone W, Menon AG. Neurofibromatosis type 1: Pathology, clinical features and molecular genetics. Brain Pathol. 1995;5:153-62.
17. Levy P, Bieche I, Leroy K, Parfait B, Wechsler J, Laurendeau I, et al. Molecular profiles of neurofibromatosis type 1-associated plexiform neurofibromas: Identification of a gene expression signature of poor prognosis. Clin Cancer Res. 2004;10:3763-71.
18. Mulvihill JJ. Neurofibromatosis. Ann NY Acad Sci. 1986;486:38-44.
19. Riccardi VM, Lewis RA. Penetrance of von Recklinghausen neurofibromatosis: A distinction between predecessors and descendants. Am J Hum Genet. 1988;42:284-9.
20. Boyd KP, Gao L, Feng R, Beasley M, Messiaen L, Korf BR, et al. Phenotypic variability among café-au-lait macules in neurofibromatosis type 1. J Am Acad Dermatol. 2010;63:440-7.
21. Knudson AG, Jr. Mutation and cancer: Statistical study of retinoblastoma. Proc Natl Acad Sci USA. 1971;68:820-3.
22. Lee MJ, Stephenson DA. Recent developments in neurofibromatosis type 1. Curr Opin Neurol. 2007;20:135-41.
23. Carey JC, Viskochil DH. Neurofibromatosis type 1: A model condition for the study of the molecular basis of variable expressivity in human disorders. Am J Med Genet. 1999;89:7-13.
24. Eichenfield LF, Levy ML, Paller AS, Riccardi VM. Guidelines of care for neurofibromatosis type 1. J Am Acad Dermatol. 1997;37:625-30.
25. Diwakar G, Hornyak TJ. Cafe-au-lait patches and senile plaques: How APPt the connection? J Invest Dermatol. 2006;126:547-50.
26. Boyd KP, Korf BR, Theos A. Neurofibromatosis type 1. J Am Acad Dermatol. 2009;61:1-14.
27. Ilyas AM, Nourissat G, Jupiter JB. Segmental neurofibromatosis of the hand and upper extremity: A case report. J Hand Surg. 2007;32:1538-42.
28. Raygada M, Arthur DC, Wayne AS, Rennert OM, Toretsky JA, Stratakis CA. Juvenile xanthogranuloma in a child with previously unsuspected neurofibromatosis type 1 and juvenile myelomonocytic leukemia. Pediatr Blood Cancer. 2010;54:173-5.
29. Orozco J, Besson A, Pulido M, Ruiz J, Linares E, Sáez MR. Neurofibromatosis tipo 1 (NF1) revisión y presentación de un caso clínico con manifestaciones bucofaciales. Avances en Odontoestomatología. 2005;21:231-9.
30. Holt GR. ENT manifestations of von Recklinghausen’s disease. Laryngoscope. 1978;88:1617-32.
31. Friedman JM, Birch PH. Type 1 neurofibromatosis: A descriptive analysis of the disorder in 1.728 patients. Am J Med Genet. 1997;70:138-43.
32. Kissil JL, Blakeley JO, Ferner RE, Huson SM, Kalamarides M, Mautner VF, et al. What’s new in neurofibromatosis? Am J Med Genet A. 2010;152A:269-83.
33. Mumoli N, Cei M, Bartolomei C, Pirillo V. A patient with loss of vision in the right eye and neurofibromatosis type 1. CMAJ. 2009;180:203-6.
34. Hope DG, Mulvihill JJ. Malignancy in neurofibromatosis. Adv Neurol. 1981;29:33-56.
35. Topsakal C, Akdemir I, Tiftikci M, Ozercan I, Aydin Y. Malignant schwannoma of the sciatic nerve originating in a spinal plexiform neurofibroma associated with neurofibromatosis type 1 -case report. Neurol Med Chir (Tokyo). 2001;41:551-5.
36. Friedrich RE, Mautner VF, Scheuer HA. Loss of heterozygosity in tumor cells of a recurrent mandibular giant cell granuloma in neurofibromatosis type 1. Anticancer Res. 2007;27:2079-83.
37. Hefti F, Bollini G, Dungl P, Fixsen J, Grill F, Ippolito E, et al. Congenital pseudarthrosis of the tibia: History, etiology, classification, and epidemiologic data. J Pediatr Orthop B. 2000;9:11-5.
38. Crawford A, Schorry E. Neurofibromatosis in children: The role of the orthopaedist. J Am Acad Orthop Surg. 1999;7:217-30.
39. Vallejo D, Lopéz J, Contreras G.Neurofibromatosis tipo 1, agenesia de peroné bilateral con acortamiento de tibia en forma triangular y mutación en el exón 24 p. K 1423E: reporte de caso y revisión de la literatura. IATREIA. 2010;23:s110.
40. McFarland B. Pseudarthrosis of the tibia in childhood. J Bone Joint Surg Br. 1951;33:36-46.
41. Cheema JI, Grissom LE, Harcke HT. Radiographic characteristics of lower-extremity bowing in children. Radiographics. 2003;23:871-80.
42. Tuncay IC, Johnston CE, 2nd, Birch JG. Spontaneous resolution of congenital anterolateral bowing of the tibia. J Pediatr Orthop. 1994;14:599-602.
43. Karol LA, Haideri NF, Halliday SE, Smitherman TB, Johnston CE, 2nd. Gait analysis and muscle strength in children with congenital pseudarthrosis of the tibia: The effect of treatment. J Pediatr Orthop. 1998;18:381-6.
44. Fixsen JA. Major congenital shortening of the lower limb and congenital pseudarthrosis of the tibia. J Pediatr Orthop B. 1995;4:142-4.
45. Lehman WB, Abdelgawad AA, Sala DA. Congenital tibial dysplasia (congenital pseudoarthrosis of the tibia): An atypical variation. J Pediatr Orthop B. 2009;18:211-3.
46. Boyd HB. Pathology and natural history of congenital pseudarthrosis of the tibia. Clin Orthop Relat Res. 1982;166:5-13.
47. Traub JA, O’Connor W, Masso PD. Congenital pseudarthrosis of the tibia: A retrospective review. J Pediatr Orthop. 1999;19:735-8.
48. Grill F, Bollini G, Dungl P, Fixsen J, Hefti F, Ippolito E, et al. Treatment approaches for congenital pseudarthrosis of tibia: Results of the EPOS multicenter study. J Pediatr Orthop B. 2000;9:75-89.
49. Erni D, De Kerviler S, Hertel R, Slongo T. Vascularised fibula grafts for early tibia reconstruction in infants with congenital pseudarthrosis. J Plast Reconstr Aesthet Surg. 2010;63:1699-704.
50. Akbarnia BA, Gabriel KR, Beckman E, Chalk D. Prevalence of scoliosis in neurofibromatosis. Spine. 1992;17(Suppl.8):S244-8.
51. Pérez LM, Marrero LO, Rochè HE, Calzado R, González C. Diagnóstico clinicoimagenológico de la neurofibromatosis tipo 1. Revista Cubana de Ortopedia y Traumatología. 2005;19 (1):47-50.
52. Mahnken AH, Staatz G, Hermanns B, Gunther RW, Weber M. Congenital pseudarthrosis of the tibia in pediatric patients: MR imaging. Am J Roentgenol. 2001;177:1025-9.
53. Lovell AT, Alexander R, Grundy EM. Silent, unstable, cervical spine injury in multiple neurofibromatosis. Anaesthesia. 1994;49:453-4.
54. Rocchietti M, De Palma C, L’Angiocola PD, Aliberti G. Neurofibromatosis type I and hypertension: A case report. Recenti Prog Med. 2008;99:602-5.
55. Prave F, Hach-Wunderle V, Hach W. Vascular manifestation of von Recklinghausen neurofibromatosis: Case report of venous dysplasia. Vasa. 2003;32:36-9.
56. Virdis R, Sigorini M, Laiolo A, Lorenzetti E, Street ME, Villani AR, et al. Neurofibromatosis type 1 and precocious puberty. J Pediatr Endocrinol Metab. 2000;13(Suppl.1):841-4.
57. Zografos GN, Vasiliadis GK, Zagouri F, Aggeli C, Korkolis D, Vogiaki S, et al. Pheochromocytoma associated with neurofibromatosis type 1: Concepts and current trends. World J Surg Oncol. 2010;8:14.
58. Yantiss RK, Rosenberg AE, Sarran L, Besmer P, Antonescu CR. Multiple gastrointestinal stromal tumors in type I neurofibromatosis: A pathologic and molecular study. Mod Pathol. 2005;18:475-84.
59. North K. Neurofibromatosis type 1. Am J Med Genet. 2000;97:119-27.
60. Hyman SL, Shores A, North KN. The nature and frequency of cognitive deficits in children with neurofibromatosis type 1. Neurology. 2005;65:1037-44.
61. North K, Joy P, Yuille D, Cocks N, Mobbs E, Hutchins P, et al. Specific learning disability in children with neurofibromatosis type 1: Significance of MRI abnormalities. Neurology. 1994;44:878-83.
62. Maertens O, De Schepper S, Vandesompele J, Brems H, Heyns I, Janssens S, et al. Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1. Am J Hum Genet. 2007;81:243-51.
Cómo citar
1.
Vallejo DL, López JE. Abordaje clínico de variantes fenotípicas en neurofibromatosis de tipo 1. rev. asoc. colomb. dermatol. cir. dematol. [Internet]. 18 de febrero de 2019 [citado 18 de abril de 2024];20(1):29-38. Disponible en: https://revista.asocolderma.org.co/index.php/asocolderma/article/view/208
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2019-02-18
Cómo citar
1.
Vallejo DL, López JE. Abordaje clínico de variantes fenotípicas en neurofibromatosis de tipo 1. rev. asoc. colomb. dermatol. cir. dematol. [Internet]. 18 de febrero de 2019 [citado 18 de abril de 2024];20(1):29-38. Disponible en: https://revista.asocolderma.org.co/index.php/asocolderma/article/view/208
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