Neurofibromatosis type 1 differential diagnosis

Template:Atherosclerosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Moises Romo M.D.

Overview

Neurofibromatosis type 1 should be differentiated from other genetic disorders who present with overlapping features, such as Von Hippel-Lindau syndrome, Carney complex, Li-Fraumeni syndrome, Gardner’s syndrome, Multiple endocrine neoplasia type 2, Cowden syndrome, Acromegaly/gigantism, Pituitary adenoma, Hyperparathyroidism, Pheochromocytoma/paraganglioma, Adrenocortical carcinoma.

Differentiating neurofibromatosis type 1 from other Diseases

Neurofibromatosis type 1 can be differentitated from other genetic disorders by the following characteristics:^[1]^[2]^[3]^[4]^[5]^[6]^[7]^[8]^[9]^[10]^[11]


Disease	Gene	Chromosome	Differentiating Features	Components of MEN			Diagnosis
Disease	Gene	Chromosome	Differentiating Features	Parathyroid	Pitutary	Pancreas	Diagnosis
Von Hippel-Lindau syndrome^[1]	Von Hippel–Lindau tumor suppressor^[1]	3p25.3^[1]	Angiomatosis,^[1] Hemangioblastomas,^[1] Pheochromocytoma,^[1] Renal cell carcinoma,^[1] Pancreatic cysts (pancreatic serous cystadenoma)^[1] Endolymphatic sac tumor,^[1] Bilateral papillary cystadenomas of the epididymis (men) or broad ligament of the uterus (women)^[1]	–	–	+	Clinical diagnosis^[1] In hereditary VHL, disease techniques such as Southern blotting and gene sequencing can be used to analyse DNA and identify mutations.^[1]
Carney complex^[2]	PRKAR1A^[2]	17q23-q24^[2]	Myxomas of the heart^[2] Hyperpigmentation of the skin (lentiginosis)^[2] Endocrine (ACTH-independent Cushing’s syndrome due to primary pigmented nodular adrenocortical disease)^[2]	–	–	–	Clinical diagnosis^[2]
Neurofibromatosis type 1^[12]	NF1^[12]	17^[12]	Scoliosis^[12] Learning disabilities^[12] Vision disorders^[12] Cutaneous lesions^[12] Epilepsy.^[12]	–	–	–	Prenatal Chorionic villus sampling or amniocentesis can be used to detect NF-1 in the fetus.^[12] Postnatal Cardinal Clinical Features” are required for positive diagnosis.^[12] Six or more café-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals.^[12] Two or more neurofibromas of any type or 1 plexiform neurofibroma^[12] Freckling in the axillary (Crowe sign) or inguinal regions^[12] Optic glioma^[12] Two or more Lisch nodules (pigmented iris hamartomas)^[12] A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis.^[12]
Li-Fraumeni syndrome^[3]	TP53^[3]	17^[3]	Early onset of diverse amount of cancers such as Sarcoma Cancers of Breast Brain Adrenal glands^[3]	–	–	–	Criteria Sarcoma at a young age (below 45)^[3] A first-degree relative diagnosed with any cancer at a young age (below 45)^[3] A first or second degree relative with any cancer diagnosed before age 60.^[3]
Gardner’s syndrome^[4]	APC^[4]	5q21^[4]	Multiple polyps in the colon^[4] Osteomas of the skull^[4] Thyroid cancer,^[4] Epidermoid cysts,^[4] Fibromas^[4] Desmoid tumors^[4]	–	–	–	Clinical diagnosis^[4] Colonoscopy^[4]
Multiple endocrine neoplasia type 2^[5]	RET^[5]	–	Medullary thyroid carcinoma (MTC)^[5] Pheochromocytoma^[5] Primary ^[5]hyperparathyroidism^[5]	+	–	–	Hypercalcemia^[5] Hypophosphatemia,^[5] Elevated parathyroid hormone,^[5] Elevated norepinephrine^[5] Criteria Two or more specific endocrine tumors Medullary thyroid carcinoma Pheochromocytoma Parathyroid hyperplasia^[5]
Cowden syndrome^[6]	PTEN^[6]	–	Hamartomas^[6]	–	–	–	PTEN mutation probability risk calculator^[6]
Acromegaly/gigantism^[7]	GNAS1^[7]	20^[7]	Enlargement of the hands, feet, nose, lips and ears, and a general thickening of the skin^[7] Hypertrichosis^[7] Hyperpigmentation^[7] Hyperhidrosis^[7] Carpal tunnel syndrome.^[7]	–	+	–	An elevated concentration of serum growth hormone (GH) and insulin-like growth factor 1(IGF-1) levels is diagnostic of acromegaly.^[7]
Pituitary adenoma^[8]	–	–	Visual field defects classically bitemporal hemianopsia^[8] Increased intracranial pressure^[8] Migraine^[8] Lateral rectus palsy^[8]	–	+	–	Elevated serum level of prolactin^[8] Elevated or decreased serum level of adrenocorticotropic hormone (ACTH)^[8] Elevated or decreased serum level of growth hormone (GH)^[8] Elevated or decreased serum level of thyroid-stimulating hormone (TSH)^[8] Elevated or decreased serum level of follicle-stimulating hormone (FSH)^[8] Elevated or decreased serum level of luteinizing hormone (LH)^[8]
Hyperparathyroidism^[9]	–	–	– Kidney stones^[9] Hypercalcemia,^[9] Constipation^[9] Peptic ulcers^[9] Depression^[9]	+	–	–	An elevated concentration of serum calcium with elevated parathyroid hormone level is diagnostic of primary hyperparathyroidism.^[9] Most consistent laboratory findings associated with the diagnosis of secondary hyperparathyroidism include elevated serum parathyroid hormone level and low to normal serum calcium.^[9] An elevated concentration of serum calcium with elevated parathyroid hormone level in post renal transplant patients is diagnostic of tertiary hyperparathyoidism.^[9]
Pheochromocytoma/paraganglioma^[10]	VHL RET NF1 SDHB SDHD^[10]	–	Characterized by Episodic hypertension^[10] Palpitations^[10] Anxiety^[10] Diaphoresis^[10] Weight loss^[10]	–	–	–	Increased catecholamines and metanephrines in plasma (blood) or through a 24-hour urine collection.^[10]
Adrenocortical carcinoma^[11]	p53^[11] Retinoblastoma h19^[11] Insulin-like growth factor II (IGF-II)^[11] p57^{kip2^[11]}	17p, 13q^[11]	Cushing syndrome (cortisol hypersecretion)^[11] Conn syndrome (aldosterone hypersecretion)^[11] virilization (testosterone hypersecretion)^[11]	–	–	–	Increased serum glucose^[11] Increased urine cortisol^[11] Serum androstenedione and dehydroepiandrosterone^[11] Low serum potassium^[11] Low plasma renin activity^[11] High serum aldosterone.^[11] Excess serum estrogen.^[11]
Adapted from Toledo SP, Lourenço DM, Toledo RA. A differential diagnosis of inherited endocrine tumors and their tumor counterparts, journal=Clinics (Sao Paulo), volume= 68, issue= 7, 07/24/2013^[13]

References

↑ ^1.00 ^1.01 ^1.02 ^1.03 ^1.04 ^1.05 ^1.06 ^1.07 ^1.08 ^1.09 ^1.10 ^1.11 ^1.12 Varshney N, Kebede AA, Owusu-Dapaah H, Lather J, Kaushik M, Bhullar JS (2017). “A Review of Von Hippel-Lindau Syndrome”. J Kidney Cancer VHL. 4 (3): 20–29. doi:10.15586/jkcvhl.2017.88. PMC 5541202. PMID 28785532.
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 Correa R, Salpea P, Stratakis CA (October 2015). “Carney complex: an update”. Eur. J. Endocrinol. 173 (4): M85–97. doi:10.1530/EJE-15-0209. PMC 4553126. PMID 26130139.
↑ ^3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 Correa H (June 2016). “Li-Fraumeni Syndrome”. J Pediatr Genet. 5 (2): 84–8. doi:10.1055/s-0036-1579759. PMC 4918696. PMID 27617148.
↑ ^4.00 ^4.01 ^4.02 ^4.03 ^4.04 ^4.05 ^4.06 ^4.07 ^4.08 ^4.09 ^4.10 ^4.11 Füredi G, Varga I, Máj C, Szilágyi A, Madácsy L, Paál Z, Altorjay Á (September 2019). “[Gardner’s syndrome, a rare disease]”. Magy Seb (in Hungarian). 72 (3): 107–111. doi:10.1556/1046.72.2019.3.4. PMID 31544480.
↑ ^5.00 ^5.01 ^5.02 ^5.03 ^5.04 ^5.05 ^5.06 ^5.07 ^5.08 ^5.09 ^5.10 ^5.11 Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Eng C. PMID 20301434. Vancouver style error: initials (help); Missing or empty |title= (help)
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 Taghavi A, Mirfazaelian H, Shirian S, Aledavood A, Akhgar A (June 2018). “Cowden syndrome”. Br J Hosp Med (Lond). 79 (6): 352–353. doi:10.12968/hmed.2018.79.6.352. PMID 29894252.
↑ ^7.00 ^7.01 ^7.02 ^7.03 ^7.04 ^7.05 ^7.06 ^7.07 ^7.08 ^7.09 Colao A, Grasso L, Giustina A, Melmed S, Chanson P, Pereira AM, Pivonello R (March 2019). “Acromegaly”. Nat Rev Dis Primers. 5 (1): 20. doi:10.1038/s41572-019-0071-6. PMID 30899019. Vancouver style error: initials (help)
↑ ^8.00 ^8.01 ^8.02 ^8.03 ^8.04 ^8.05 ^8.06 ^8.07 ^8.08 ^8.09 ^8.10 ^8.11 Møller MW, Andersen MS, Glintborg D, Pedersen CB, Halle B, Kristensen BW, Poulsen FR (May 2019). “[Pituitary adenoma]”. Ugeskr. Laeg. (in Danish). 181 (20). PMID 31124446.
↑ ^9.00 ^9.01 ^9.02 ^9.03 ^9.04 ^9.05 ^9.06 ^9.07 ^9.08 ^9.09 Bilezikian JP, Bandeira L, Khan A, Cusano NE (January 2018). “Hyperparathyroidism”. Lancet. 391 (10116): 168–178. doi:10.1016/S0140-6736(17)31430-7. PMID 28923463.
↑ ^10.0 ^10.1 ^10.2 ^10.3 ^10.4 ^10.5 ^10.6 ^10.7 ^10.8 Farrugia FA, Charalampopoulos A (July 2019). “Pheochromocytoma”. Endocr Regul. 53 (3): 191–212. doi:10.2478/enr-2019-0020. PMID 31517632.
↑ ^11.00 ^11.01 ^11.02 ^11.03 ^11.04 ^11.05 ^11.06 ^11.07 ^11.08 ^11.09 ^11.10 ^11.11 ^11.12 ^11.13 ^11.14 ^11.15 ^11.16 Kranjčević K (December 2016). “[ADRENOCORTICAL CARCINOMA]”. Acta Med Croatica. 70 (4–5): 315–8. PMID 29087170.
↑ ^12.00 ^12.01 ^12.02 ^12.03 ^12.04 ^12.05 ^12.06 ^12.07 ^12.08 ^12.09 ^12.10 ^12.11 ^12.12 ^12.13 ^12.14 ^12.15 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.
↑ Toledo SP, Lourenço DM, Toledo RA (July 2013). “A differential diagnosis of inherited endocrine tumors and their tumor counterparts”. Clinics (Sao Paulo). 68 (7): 1039–56. doi:10.6061/clinics/2013(07)24. PMC 3715026. PMID 23917672.

Template:WH Template:WS

[pmid28785532-1] 1.00 ^1.01 ^1.02 ^1.03 ^1.04 ^1.05 ^1.06 ^1.07 ^1.08 ^1.09 ^1.10 ^1.11 ^1.12 Varshney N, Kebede AA, Owusu-Dapaah H, Lather J, Kaushik M, Bhullar JS (2017). “A Review of Von Hippel-Lindau Syndrome”. J Kidney Cancer VHL. 4 (3): 20–29. doi:10.15586/jkcvhl.2017.88. PMC 5541202. PMID 28785532.

[pmid26130139-2] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 ^2.5 ^2.6 ^2.7 Correa R, Salpea P, Stratakis CA (October 2015). “Carney complex: an update”. Eur. J. Endocrinol. 173 (4): M85–97. doi:10.1530/EJE-15-0209. PMC 4553126. PMID 26130139.

[pmid27617148-3] 3.0 ^3.1 ^3.2 ^3.3 ^3.4 ^3.5 ^3.6 ^3.7 Correa H (June 2016). “Li-Fraumeni Syndrome”. J Pediatr Genet. 5 (2): 84–8. doi:10.1055/s-0036-1579759. PMC 4918696. PMID 27617148.

[pmid31544480-4] 4.00 ^4.01 ^4.02 ^4.03 ^4.04 ^4.05 ^4.06 ^4.07 ^4.08 ^4.09 ^4.10 ^4.11 Füredi G, Varga I, Máj C, Szilágyi A, Madácsy L, Paál Z, Altorjay Á (September 2019). “[Gardner’s syndrome, a rare disease]”. Magy Seb (in Hungarian). 72 (3): 107–111. doi:10.1556/1046.72.2019.3.4. PMID 31544480.

[pmid20301434-5] 5.00 ^5.01 ^5.02 ^5.03 ^5.04 ^5.05 ^5.06 ^5.07 ^5.08 ^5.09 ^5.10 ^5.11 Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Eng C. PMID 20301434. Vancouver style error: initials (help); Missing or empty |title= (help)

[pmid29894252-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 Taghavi A, Mirfazaelian H, Shirian S, Aledavood A, Akhgar A (June 2018). “Cowden syndrome”. Br J Hosp Med (Lond). 79 (6): 352–353. doi:10.12968/hmed.2018.79.6.352. PMID 29894252.

[pmid30899019-7] 7.00 ^7.01 ^7.02 ^7.03 ^7.04 ^7.05 ^7.06 ^7.07 ^7.08 ^7.09 Colao A, Grasso L, Giustina A, Melmed S, Chanson P, Pereira AM, Pivonello R (March 2019). “Acromegaly”. Nat Rev Dis Primers. 5 (1): 20. doi:10.1038/s41572-019-0071-6. PMID 30899019. Vancouver style error: initials (help)

[pmid31124446-8] 8.00 ^8.01 ^8.02 ^8.03 ^8.04 ^8.05 ^8.06 ^8.07 ^8.08 ^8.09 ^8.10 ^8.11 Møller MW, Andersen MS, Glintborg D, Pedersen CB, Halle B, Kristensen BW, Poulsen FR (May 2019). “[Pituitary adenoma]”. Ugeskr. Laeg. (in Danish). 181 (20). PMID 31124446.

[pmid28923463-9] 9.00 ^9.01 ^9.02 ^9.03 ^9.04 ^9.05 ^9.06 ^9.07 ^9.08 ^9.09 Bilezikian JP, Bandeira L, Khan A, Cusano NE (January 2018). “Hyperparathyroidism”. Lancet. 391 (10116): 168–178. doi:10.1016/S0140-6736(17)31430-7. PMID 28923463.

[pmid31517632-10] 10.0 ^10.1 ^10.2 ^10.3 ^10.4 ^10.5 ^10.6 ^10.7 ^10.8 Farrugia FA, Charalampopoulos A (July 2019). “Pheochromocytoma”. Endocr Regul. 53 (3): 191–212. doi:10.2478/enr-2019-0020. PMID 31517632.

[pmid29087170-11] 11.00 ^11.01 ^11.02 ^11.03 ^11.04 ^11.05 ^11.06 ^11.07 ^11.08 ^11.09 ^11.10 ^11.11 ^11.12 ^11.13 ^11.14 ^11.15 ^11.16 Kranjčević K (December 2016). “[ADRENOCORTICAL CARCINOMA]”. Acta Med Croatica. 70 (4–5): 315–8. PMID 29087170.

[pmid29478615-12] 12.00 ^12.01 ^12.02 ^12.03 ^12.04 ^12.05 ^12.06 ^12.07 ^12.08 ^12.09 ^12.10 ^12.11 ^12.12 ^12.13 ^12.14 ^12.15 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.

[pmid239176722-13] Toledo SP, Lourenço DM, Toledo RA (July 2013). “A differential diagnosis of inherited endocrine tumors and their tumor counterparts”. Clinics (Sao Paulo). 68 (7): 1039–56. doi:10.6061/clinics/2013(07)24. PMC 3715026. PMID 23917672.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

Neurofibromatosis type 1 differential diagnosis

Overview

Differentiating neurofibromatosis type 1 from other Diseases

References

Looking for the patient version?