Neurofibromatosis type 1 physical examination
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo M.D.
Overview
Overview
Neurofibromatosis type 1 physical examination may vary widely among patients. The most common features are the presence of neurofibromas, plexiform neurofibromas, Lisch nodules, cafe au lait macules (CALM), delayed puberty features, and cognitive impairment. Neurofibromatosis type 1 may be diagnosed clinically with great specificity and sensitivity by the presence of 2 characteristic features on physical examination, although many children with the NF1 gene mutation may not meet the criteria at age 1, but will do so at 8 years old in 97% of the cases.
Physical Examination
Physical Examination
- Physical examination of patients with neurofibromatosis type 1 is remarkable for the presence of neurofibromas, plexiform neurofibromas, Lisch nodules, cafe au lait macules, delayed puberty features, and cognitive impairment.[1]
- Neurofibromatosis type 1 has a great variability among the patients, while some individuals may have few small neurofibromas, others may have multiple large masses.[1]
- Neurofibromas may appear in any part of the body, although they are much more common in the skin.[1]
- The presence of 2 of the following features on physical examination is sufficient for clinical diagnosis of neurofibromatosis type 1:[2][3]
- ≥2 neurofibromas
- ≥1 plexiform neurofibromas
- ≥6 cafe-au-lait macules (>0.5 cm before puberty; >1.5 cm after puberty)
- Skinfold freckling
- ≥2 Lisch nodules
- Tibial pseudoarthrosis or bone dysplasias
- Optic pathway glioma
- First-degree family relative with neurofibromatosis type 1 clinically diagnosed
- Approximately 46% of the children with a NF1 gene mutation may not meet clinical criteria for diagnosis at age 1, but will do so at 8 years old in 97% of the cases, while they all completly fullfill diagnostic criteria by age 20.[4][5]
- Tumors may already be present at the time of birth, but often begin to appear at puberty.[1]
Appearance of the Patient
- Delayed puberty features (present in 80 to 99% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Cognitive impairment (present in 80 to 99% of the individuals)[8][9][7]
- Ataxic (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Genu valgum (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Speech impairment (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- High stature (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Short stature (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Abnormal hair quantity (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Precocious puberty features (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
Vital Signs
- High blood pressure with normal pulse pressure (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
Skin
- Neurofibromas are the most common type of tumor in neurofibromatosis type 1 (present in 80–99% of the individuals). Skin neurofibromas can be classified as pedunculated, subcutaneous, or sessile._Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][10][11][12][13][7]
- Plexiform neurofibromas are potentialy malignant.They have been described as “a bag of worms” (present in 80 to 99% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][14][11][13][15]
- Generalized hyperpigmentation (present in 80 to 99% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][16]
- Cafe au lait spots (present in 80 to 99% of the individuals)[13][7][17]
- Lipomas (present in 80 to 99% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Macules (present in 80 to 99% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Melanocytic nevus (present in 80 to 99% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Hypopigmented skin patches (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Hypertrophy of fungiform papillae (present in 5 to 29% of the individuals)[18]
- Bruises (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Skin freckling (present in 5 to 29% of the individuals)[13][19]
HEENT
- Lisch nodules (present in 80 to 99% of the individuals)[13][7][20]
- Hearing impairment (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Heterochromia iridis (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Proptosis (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Hydrocephalus (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Macrocephaly (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Abnormal electroretinogram (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Abnormal eyelid morphology (present in 5 to 29% of the individuals)[13]
- Abnormality of retinal pigmentation (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Cataract (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Chorioretinal coloboma (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Corneal opacity (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Glaucoma (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Myopia (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Hypertelorism (present in 1 to 4% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Optic nerve glioma (present in 1 to 4% of the individuals)[13]
Neck
- Parathyroid adenoma (present in 1 to 4% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
Chest
- Respiratory system anomalies (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Pectus excavatum (present in 1 to 4% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Breast cancer (present in 1 to 4% of the individuals)[13]
Cardiovascular
- Arterial stenosis (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
Abdomen
- Neoplasm of the gastrointestinal tract (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Pheochromocytoma (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
Back
- Scoliosis (present in 5 to 29% of the individuals)[13][7]
- Kyphosis (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Spina bifida (present in 1 to 4% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6] [7]
Genitourinary
- Cryptorchidism (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Abnormality of the upper urinary tract (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Urinary tract neoplasm (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Renal artery stenosis (present in 1 to 4% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
Neuromuscular
- Paresthesias (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
Extremities
- Genu valgum (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Slender long bones (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7]
- Skeletal dysplasia (present in 30 to 79% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6][7][18][21]
- Joint stiffness (present in 5 to 29% of the individuals)_Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program-6|[6]
- Tibial pseudarthrosis (present in 1 to 4% of the individuals)[13]
References
References
- ↑ 1.0 1.1 1.2 1.3 “scielo.isciii.es” (PDF).
- ↑ Cimino PJ, Gutmann DH (2018). “Neurofibromatosis type 1”. Handb Clin Neurol. 148: 799–811. doi:10.1016/B978-0-444-64076-5.00051-X. PMID 29478615.
- ↑ Boyd KP, Korf BR, Theos A (July 2009). “Neurofibromatosis type 1”. J. Am. Acad. Dermatol. 61 (1): 1–14, quiz 15–6. doi:10.1016/j.jaad.2008.12.051. PMID 19539839.
- ↑ DeBella K, Szudek J, Friedman JM (March 2000). “Use of the national institutes of health criteria for diagnosis of neurofibromatosis 1 in children”. Pediatrics. 105 (3 Pt 1): 608–14. doi:10.1542/peds.105.3.608. PMID 10699117.
- ↑ Boyd KP, Korf BR, Theos A (July 2009). “Neurofibromatosis type 1”. J. Am. Acad. Dermatol. 61 (1): 1–14, quiz 15–6. doi:10.1016/j.jaad.2008.12.051. PMC 2716546. PMID 19539839.
- ↑ _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-0|6.00 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-1|6.01 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-2|6.02 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-3|6.03 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-4|6.04 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-5|6.05 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-6|6.06 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-7|6.07 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-8|6.08 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-9|6.09 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-10|6.10 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-11|6.11 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-12|6.12 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-13|6.13 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-14|6.14 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-15|6.15 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-16|6.16 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-17|6.17 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-18|6.18 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-19|6.19 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-20|6.20 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-21|6.21 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-22|6.22 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-23|6.23 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-24|6.24 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-25|6.25 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-26|6.26 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-27|6.27 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-28|6.28 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-29|6.29 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-30|6.30 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-31|6.31 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-32|6.32 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-33|6.33 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-34|6.34 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-35|6.35 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-36|6.36 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-37|6.37 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-38|6.38 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-39|6.39 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-40|6.40 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-41|6.41 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-42|6.42 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-43|6.43 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-44|6.44 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-45|6.45 _Genetic_and_Rare_Diseases_Information_Center_(GARD)_–_an_NCATS_Program_6-46|6.46 “Neurofibromatosis type 1 | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program”.
- ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 7.16 Radtke HB, Sebold CD, Allison C, Haidle JL, Schneider G (August 2007). “Neurofibromatosis type 1 in genetic counseling practice: recommendations of the National Society of Genetic Counselors”. J Genet Couns. 16 (4): 387–407. doi:10.1007/s10897-007-9101-8. PMC 6338721. PMID 17636453.
- ↑ Hyman, SL. et al.(2005). The Nature and Frequency of Cognitive Deficits in Children with Neurofibromatosis Type 1. Neurology, 65, 1037-1044.
- ↑ Hyman, S.L. et al. (2003). Natural History of Neuropsychological Ability and T2-Hyperintensities in Patients with Neurofibromatosis Type 1. Neurology, 60(7), 1139-1145.
- ↑ Friedman JM, Birch PH (May 1997). “Type 1 neurofibromatosis: a descriptive analysis of the disorder in 1,728 patients”. Am. J. Med. Genet. 70 (2): 138–43. doi:10.1002/(sici)1096-8628(19970516)70:2<138::aid-ajmg7>3.0.co;2-u. PMID 9128932.
- ↑ 11.0 11.1 Anderson JL, Gutmann DH (2015). “Neurofibromatosis type 1”. Handb Clin Neurol. 132: 75–86. doi:10.1016/B978-0-444-62702-5.00004-4. PMID 26564071.
- ↑ . doi:10.1002/(SICI)1096-8628(19990326)89:1<23::AID-AJMG6>3.0.CO;2-%23. Missing or empty
|title=(help) - ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 Gutmann DH, Ferner RE, Listernick RH, Korf BR, Wolters PL, Johnson KJ (February 2017). “Neurofibromatosis type 1”. Nat Rev Dis Primers. 3: 17004. doi:10.1038/nrdp.2017.4. PMID 28230061.
- ↑ Mautner VF, Asuagbor FA, Dombi E, Fünsterer C, Kluwe L, Wenzel R, Widemann BC, Friedman JM (August 2008). “Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1”. Neuro-oncology. 10 (4): 593–8. doi:10.1215/15228517-2008-011. PMC 2666233. PMID 18559970.
- ↑ Evans DG, Baser ME, McGaughran J, Sharif S, Howard E, Moran A (May 2002). “Malignant peripheral nerve sheath tumours in neurofibromatosis 1”. J. Med. Genet. 39 (5): 311–4. doi:10.1136/jmg.39.5.311. PMID 12011145.
- ↑ Maertens O, De Schepper S, Vandesompele J, Brems H, Heyns I, Janssens S, Speleman F, Legius E, Messiaen L (August 2007). “Molecular dissection of isolated disease features in mosaic neurofibromatosis type 1”. Am. J. Hum. Genet. 81 (2): 243–51. doi:10.1086/519562. PMID 17668375.
- ↑ Landau M, Krafchik BR (June 1999). “The diagnostic value of café-au-lait macules”. J. Am. Acad. Dermatol. 40 (6 Pt 1): 877–90, quiz 891–2. doi:10.1016/s0190-9622(99)70075-7. PMID 10365918.
- ↑ 18.0 18.1 “scielo.isciii.es” (PDF).
- ↑ Huson SM, Harper PS, Compston DA (December 1988). “Von Recklinghausen neurofibromatosis. A clinical and population study in south-east Wales”. Brain. 111 ( Pt 6): 1355–81. doi:10.1093/brain/111.6.1355. PMID 3145091.
- ↑ Huson S, Jones D, Beck L (March 1987). “Ophthalmic manifestations of neurofibromatosis”. Br J Ophthalmol. 71 (3): 235–8. doi:10.1136/bjo.71.3.235. PMID 3103673.
- ↑ Lammert M, Kappler M, Mautner VF, Lammert K, Störkel S, Friedman JM, Atkins D (September 2005). “Decreased bone mineral density in patients with neurofibromatosis 1”. Osteoporos Int. 16 (9): 1161–6. doi:10.1007/s00198-005-1940-2. PMID 15988556.
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