U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Neuroblastoma, susceptibility to, 2(NBLST2)

MedGen UID:
416607
Concept ID:
C2751682
Finding
Synonym: Neuroblastoma 2
 
Gene (location): PHOX2B (4p13)
 
Monarch Initiative: MONDO:0700041
OMIM®: 613013

Definition

Neuroblastoma occurs most often in children before age 5 and rarely occurs in adults.

In addition, neuroblastoma tumors can release hormones that may cause other signs and symptoms such as high blood pressure, rapid heartbeat, flushing of the skin, and sweating. In rare instances, individuals with neuroblastoma may develop opsoclonus myoclonus syndrome, which causes rapid eye movements and jerky muscle motions. This condition occurs when the immune system malfunctions and attacks nerve tissue.

Individuals with neuroblastoma may develop general signs and symptoms such as irritability, fever, tiredness (fatigue), pain, loss of appetite, weight loss, or diarrhea. More specific signs and symptoms depend on the location of the tumor and where it has spread. A tumor in the abdomen can cause abdominal swelling. A tumor in the chest may lead to difficulty breathing. A tumor in the neck can cause nerve damage known as Horner syndrome, which leads to drooping eyelids, small pupils, decreased sweating, and red skin. Tumor metastasis to the bone can cause bone pain, bruises, pale skin, or dark circles around the eyes. Tumors in the backbone can press on the spinal cord and cause weakness, numbness, or paralysis in the arms or legs. A rash of bluish or purplish bumps that look like blueberries indicates that the neuroblastoma has spread to the skin.

Neuroblastoma is a type of cancer that most often affects children. Neuroblastoma occurs when immature nerve cells called neuroblasts become abnormal and multiply uncontrollably to form a tumor. Most commonly, the tumor originates in the nerve tissue of the adrenal gland located above each kidney. Other common sites for tumors to form include the nerve tissue in the abdomen, chest, neck, or pelvis. Neuroblastoma can spread (metastasize) to other parts of the body such as the bones, liver, or skin. [from MedlinePlus Genetics]

Clinical features

From HPO
Neuroblastoma
MedGen UID:
18012
Concept ID:
C0027819
Neoplastic Process
ALK-related neuroblastic tumor susceptibility is characterized by increased risk for neuroblastic tumors including neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. Neuroblastoma is a more malignant tumor and ganglioneuroma a more benign tumor. Depending on the histologic findings, ganglioneuroblastoma can behave in a more aggressive fashion, like neuroblastoma, or in a benign fashion, like ganglioneuroma. Preliminary data from the ten reported families with ALK-related neuroblastic tumor susceptibility suggest an overall penetrance of approximately 57% with the risk for neuroblastic tumor development highest in infancy and decreasing by late childhood.
Ganglioneuroblastoma
MedGen UID:
60218
Concept ID:
C0206718
Neoplastic Process
Ganglioneuroblastoma is a rare type of primitive neuroectodermal tumor (PNET; see this term), affecting almost exclusively infants and young children under the age of 10, usually occurring in the posterior mediastinum, adrenal medulla and extra-adrenal retroperitoneum (but sometimes in the neck and pelvis), with metastasis most often presenting in the bones, and characterized clinically by pain, stridor, shortness of breath, peripheral neurological signs, superior vena cava syndrome and congenital Horner syndrome (see this term), depending on the location of the tumor.
Ganglioneuroma
MedGen UID:
6545
Concept ID:
C0017075
Neoplastic Process
A benign neoplasm that usually arises from the sympathetic trunk in the mediastinum, representing a tumor of the sympathetic nerve fibers arising from neural crest cells.
Aganglionic megacolon
MedGen UID:
5559
Concept ID:
C0019569
Disease or Syndrome
The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid (Amiel et al., 2008). Total colonic aganglionosis and total intestinal HSCR also occur. Genetic Heterogeneity of Hirschsprung Disease Several additional loci for isolated Hirschsprung disease have been mapped. HSCR2 (600155) is associated with variation in the EDNRB gene (131244) on 13q22; HSCR3 (613711) is associated with variation in the GDNF gene (600837) on 5p13; HSCR4 (613712) is associated with variation in the EDN3 gene (131242) on 20q13; HSCR5 (600156) maps to 9q31; HSCR6 (606874) maps to 3p21; HSCR7 (606875) maps to 19q12; HSCR8 (608462) maps to 16q23; and HSCR9 (611644) maps to 4q31-q32. HSCR also occurs as a feature of several syndromes including the Waardenburg-Shah syndrome (277580), Mowat-Wilson syndrome (235730), Goldberg-Shprintzen syndrome (609460), and congenital central hypoventilation syndrome (CCHS; 209880). Whereas mendelian modes of inheritance have been described for syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance. The development of surgical procedures decreased mortality and morbidity, which allowed the emergence of familial cases. HSCR occurs as an isolated trait in 70% of patients, is associated with chromosomal anomaly in 12% of cases, and occurs with additional congenital anomalies in 18% of cases (summary by Amiel et al., 2008).

Professional guidelines

PubMed

Kafoud A, Salahuddin Z, Ibrahim RS, Al-Janahi R, Mazurakova A, Kubatka P, Büsselberg D
Biomolecules 2023 Mar 20;13(3) doi: 10.3390/biom13030563. PMID: 36979499Free PMC Article
Hashemi M, Sarabandi S, Karami S, Śmieja J, Moazeni-Roodi A, Ghavami S, Łos MJ
J Cell Mol Med 2020 Jan;24(2):1160-1168. Epub 2019 Dec 12 doi: 10.1111/jcmm.14836. PMID: 31830377Free PMC Article
Hungate EA, Applebaum MA, Skol AD, Vaksman Z, Diamond M, McDaniel L, Volchenboum SL, Stranger BE, Maris JM, Diskin SJ, Onel K, Cohn SL
J Natl Cancer Inst 2017 Oct 1;109(10) doi: 10.1093/jnci/djx093. PMID: 29117357Free PMC Article

Recent clinical studies

Etiology

Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article
Ritenour LE, Randall MP, Bosse KR, Diskin SJ
Cell Tissue Res 2018 May;372(2):287-307. Epub 2018 Mar 27 doi: 10.1007/s00441-018-2820-3. PMID: 29589100Free PMC Article
Kamihara J, Bourdeaut F, Foulkes WD, Molenaar JJ, Mossé YP, Nakagawara A, Parareda A, Scollon SR, Schneider KW, Skalet AH, States LJ, Walsh MF, Diller LR, Brodeur GM
Clin Cancer Res 2017 Jul 1;23(13):e98-e106. doi: 10.1158/1078-0432.CCR-17-0652. PMID: 28674118Free PMC Article
Telomeres Mendelian Randomization Collaboration, Haycock PC, Burgess S, Nounu A, Zheng J, Okoli GN, Bowden J, Wade KH, Timpson NJ, Evans DM, Willeit P, Aviv A, Gaunt TR, Hemani G, Mangino M, Ellis HP, Kurian KM, Pooley KA, Eeles RA, Lee JE, Fang S, Chen WV, Law MH, Bowdler LM, Iles MM, Yang Q, Worrall BB, Markus HS, Hung RJ, Amos CI, Spurdle AB, Thompson DJ, O'Mara TA, Wolpin B, Amundadottir L, Stolzenberg-Solomon R, Trichopoulou A, Onland-Moret NC, Lund E, Duell EJ, Canzian F, Severi G, Overvad K, Gunter MJ, Tumino R, Svenson U, van Rij A, Baas AF, Bown MJ, Samani NJ, van t'Hof FNG, Tromp G, Jones GT, Kuivaniemi H, Elmore JR, Johansson M, Mckay J, Scelo G, Carreras-Torres R, Gaborieau V, Brennan P, Bracci PM, Neale RE, Olson SH, Gallinger S, Li D, Petersen GM, Risch HA, Klein AP, Han J, Abnet CC, Freedman ND, Taylor PR, Maris JM, Aben KK, Kiemeney LA, Vermeulen SH, Wiencke JK, Walsh KM, Wrensch M, Rice T, Turnbull C, Litchfield K, Paternoster L, Standl M, Abecasis GR, SanGiovanni JP, Li Y, Mijatovic V, Sapkota Y, Low SK, Zondervan KT, Montgomery GW, Nyholt DR, van Heel DA, Hunt K, Arking DE, Ashar FN, Sotoodehnia N, Woo D, Rosand J, Comeau ME, Brown WM, Silverman EK, Hokanson JE, Cho MH, Hui J, Ferreira MA, Thompson PJ, Morrison AC, Felix JF, Smith NL, Christiano AM, Petukhova L, Betz RC, Fan X, Zhang X, Zhu C, Langefeld CD, Thompson SD, Wang F, Lin X, Schwartz DA, Fingerlin T, Rotter JI, Cotch MF, Jensen RA, Munz M, Dommisch H, Schaefer AS, Han F, Ollila HM, Hillary RP, Albagha O, Ralston SH, Zeng C, Zheng W, Shu XO, Reis A, Uebe S, Hüffmeier U, Kawamura Y, Otowa T, Sasaki T, Hibberd ML, Davila S, Xie G, Siminovitch K, Bei JX, Zeng YX, Försti A, Chen B, Landi S, Franke A, Fischer A, Ellinghaus D, Flores C, Noth I, Ma SF, Foo JN, Liu J, Kim JW, Cox DG, Delattre O, Mirabeau O, Skibola CF, Tang CS, Garcia-Barcelo M, Chang KP, Su WH, Chang YS, Martin NG, Gordon S, Wade TD, Lee C, Kubo M, Cha PC, Nakamura Y, Levy D, Kimura M, Hwang SJ, Hunt S, Spector T, Soranzo N, Manichaikul AW, Barr RG, Kahali B, Speliotes E, Yerges-Armstrong LM, Cheng CY, Jonas JB, Wong TY, Fogh I, Lin K, Powell JF, Rice K, Relton CL, Martin RM, Davey Smith G
JAMA Oncol 2017 May 1;3(5):636-651. doi: 10.1001/jamaoncol.2016.5945. PMID: 28241208Free PMC Article
Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei JS, Auclair D, Carter SL, Cibulskis K, Hanna M, Kiezun A, Kim J, Lawrence MS, Lichenstein L, McKenna A, Pedamallu CS, Ramos AH, Shefler E, Sivachenko A, Sougnez C, Stewart C, Ally A, Birol I, Chiu R, Corbett RD, Hirst M, Jackman SD, Kamoh B, Khodabakshi AH, Krzywinski M, Lo A, Moore RA, Mungall KL, Qian J, Tam A, Thiessen N, Zhao Y, Cole KA, Diamond M, Diskin SJ, Mosse YP, Wood AC, Ji L, Sposto R, Badgett T, London WB, Moyer Y, Gastier-Foster JM, Smith MA, Guidry Auvil JM, Gerhard DS, Hogarty MD, Jones SJ, Lander ES, Gabriel SB, Getz G, Seeger RC, Khan J, Marra MA, Meyerson M, Maris JM
Nat Genet 2013 Mar;45(3):279-84. Epub 2013 Jan 20 doi: 10.1038/ng.2529. PMID: 23334666Free PMC Article

Diagnosis

Weichert-Leahey N, Shi H, Tao T, Oldridge DA, Durbin AD, Abraham BJ, Zimmerman MW, Zhu S, Wood AC, Reyon D, Joung JK, Young RA, Diskin SJ, Maris JM, Look AT
J Clin Invest 2023 May 15;133(10) doi: 10.1172/JCI166919. PMID: 37183825Free PMC Article
Shimazaki K, Kurokawa R, Franson A, Kurokawa M, Baba A, Bou-Maroun L, Kim J, Moritani T
J Neuroimaging 2023 May-Jun;33(3):359-367. Epub 2023 Feb 20 doi: 10.1111/jon.13095. PMID: 36806312
Egolf LE, Vaksman Z, Lopez G, Rokita JL, Modi A, Basta PV, Hakonarson H, Olshan AF, Diskin SJ
Am J Hum Genet 2019 Sep 5;105(3):658-668. Epub 2019 Aug 29 doi: 10.1016/j.ajhg.2019.07.020. PMID: 31474320Free PMC Article
Kamihara J, Bourdeaut F, Foulkes WD, Molenaar JJ, Mossé YP, Nakagawara A, Parareda A, Scollon SR, Schneider KW, Skalet AH, States LJ, Walsh MF, Diller LR, Brodeur GM
Clin Cancer Res 2017 Jul 1;23(13):e98-e106. doi: 10.1158/1078-0432.CCR-17-0652. PMID: 28674118Free PMC Article
Halperin EC
Int J Radiat Oncol Biol Phys 2000 Apr 1;47(1):171-8. doi: 10.1016/s0360-3016(00)00424-7. PMID: 10758320

Therapy

Kafoud A, Salahuddin Z, Ibrahim RS, Al-Janahi R, Mazurakova A, Kubatka P, Büsselberg D
Biomolecules 2023 Mar 20;13(3) doi: 10.3390/biom13030563. PMID: 36979499Free PMC Article
Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article
Liu Y, Eaton ED, Wills TE, McCann SK, Antonic A, Howells DW
Transl Stroke Res 2018 Dec;9(6):564-574. Epub 2018 Mar 23 doi: 10.1007/s12975-018-0620-4. PMID: 29572690Free PMC Article
Moulik NR, Kumar A, Agrawal S
Indian J Med Res 2017 Aug;146(2):163-174. doi: 10.4103/ijmr.IJMR_275_15. PMID: 29265017Free PMC Article
Telomeres Mendelian Randomization Collaboration, Haycock PC, Burgess S, Nounu A, Zheng J, Okoli GN, Bowden J, Wade KH, Timpson NJ, Evans DM, Willeit P, Aviv A, Gaunt TR, Hemani G, Mangino M, Ellis HP, Kurian KM, Pooley KA, Eeles RA, Lee JE, Fang S, Chen WV, Law MH, Bowdler LM, Iles MM, Yang Q, Worrall BB, Markus HS, Hung RJ, Amos CI, Spurdle AB, Thompson DJ, O'Mara TA, Wolpin B, Amundadottir L, Stolzenberg-Solomon R, Trichopoulou A, Onland-Moret NC, Lund E, Duell EJ, Canzian F, Severi G, Overvad K, Gunter MJ, Tumino R, Svenson U, van Rij A, Baas AF, Bown MJ, Samani NJ, van t'Hof FNG, Tromp G, Jones GT, Kuivaniemi H, Elmore JR, Johansson M, Mckay J, Scelo G, Carreras-Torres R, Gaborieau V, Brennan P, Bracci PM, Neale RE, Olson SH, Gallinger S, Li D, Petersen GM, Risch HA, Klein AP, Han J, Abnet CC, Freedman ND, Taylor PR, Maris JM, Aben KK, Kiemeney LA, Vermeulen SH, Wiencke JK, Walsh KM, Wrensch M, Rice T, Turnbull C, Litchfield K, Paternoster L, Standl M, Abecasis GR, SanGiovanni JP, Li Y, Mijatovic V, Sapkota Y, Low SK, Zondervan KT, Montgomery GW, Nyholt DR, van Heel DA, Hunt K, Arking DE, Ashar FN, Sotoodehnia N, Woo D, Rosand J, Comeau ME, Brown WM, Silverman EK, Hokanson JE, Cho MH, Hui J, Ferreira MA, Thompson PJ, Morrison AC, Felix JF, Smith NL, Christiano AM, Petukhova L, Betz RC, Fan X, Zhang X, Zhu C, Langefeld CD, Thompson SD, Wang F, Lin X, Schwartz DA, Fingerlin T, Rotter JI, Cotch MF, Jensen RA, Munz M, Dommisch H, Schaefer AS, Han F, Ollila HM, Hillary RP, Albagha O, Ralston SH, Zeng C, Zheng W, Shu XO, Reis A, Uebe S, Hüffmeier U, Kawamura Y, Otowa T, Sasaki T, Hibberd ML, Davila S, Xie G, Siminovitch K, Bei JX, Zeng YX, Försti A, Chen B, Landi S, Franke A, Fischer A, Ellinghaus D, Flores C, Noth I, Ma SF, Foo JN, Liu J, Kim JW, Cox DG, Delattre O, Mirabeau O, Skibola CF, Tang CS, Garcia-Barcelo M, Chang KP, Su WH, Chang YS, Martin NG, Gordon S, Wade TD, Lee C, Kubo M, Cha PC, Nakamura Y, Levy D, Kimura M, Hwang SJ, Hunt S, Spector T, Soranzo N, Manichaikul AW, Barr RG, Kahali B, Speliotes E, Yerges-Armstrong LM, Cheng CY, Jonas JB, Wong TY, Fogh I, Lin K, Powell JF, Rice K, Relton CL, Martin RM, Davey Smith G
JAMA Oncol 2017 May 1;3(5):636-651. doi: 10.1001/jamaoncol.2016.5945. PMID: 28241208Free PMC Article

Prognosis

Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV
Nat Rev Endocrinol 2018 Dec;15(1):33-51. doi: 10.1038/s41574-018-0115-0. PMID: 30443043Free PMC Article
Ritenour LE, Randall MP, Bosse KR, Diskin SJ
Cell Tissue Res 2018 May;372(2):287-307. Epub 2018 Mar 27 doi: 10.1007/s00441-018-2820-3. PMID: 29589100Free PMC Article
Rickman DS, Schulte JH, Eilers M
Cancer Discov 2018 Feb;8(2):150-163. Epub 2018 Jan 22 doi: 10.1158/2159-8290.CD-17-0273. PMID: 29358508
Sridhar S, Al-Moallem B, Kamal H, Terrile M, Stallings RL
Mol Diagn Ther 2013 Apr;17(2):63-9. doi: 10.1007/s40291-013-0019-6. PMID: 23329364
Halperin EC
Int J Radiat Oncol Biol Phys 2000 Apr 1;47(1):171-8. doi: 10.1016/s0360-3016(00)00424-7. PMID: 10758320

Clinical prediction guides

Shimazaki K, Kurokawa R, Franson A, Kurokawa M, Baba A, Bou-Maroun L, Kim J, Moritani T
J Neuroimaging 2023 May-Jun;33(3):359-367. Epub 2023 Feb 20 doi: 10.1111/jon.13095. PMID: 36806312
Li Y, Lu T, Wang J, Zhuo Z, Miao L, Yang Z, Zhang J, Cheng J, Zhou H, Li S, Li L, He J, Li A
Aging (Albany NY) 2021 Dec 12;13(23):25426-25439. doi: 10.18632/aging.203760. PMID: 34897032Free PMC Article
Bielarz V, Willemart K, Avalosse N, De Swert K, Lotfi R, Lejeune N, Poulain F, Ninanne N, Gilloteaux J, Gillet N, Nicaise C
Brain Res 2021 May 1;1758:147344. Epub 2021 Feb 5 doi: 10.1016/j.brainres.2021.147344. PMID: 33556379Free PMC Article
Ritenour LE, Randall MP, Bosse KR, Diskin SJ
Cell Tissue Res 2018 May;372(2):287-307. Epub 2018 Mar 27 doi: 10.1007/s00441-018-2820-3. PMID: 29589100Free PMC Article
Telomeres Mendelian Randomization Collaboration, Haycock PC, Burgess S, Nounu A, Zheng J, Okoli GN, Bowden J, Wade KH, Timpson NJ, Evans DM, Willeit P, Aviv A, Gaunt TR, Hemani G, Mangino M, Ellis HP, Kurian KM, Pooley KA, Eeles RA, Lee JE, Fang S, Chen WV, Law MH, Bowdler LM, Iles MM, Yang Q, Worrall BB, Markus HS, Hung RJ, Amos CI, Spurdle AB, Thompson DJ, O'Mara TA, Wolpin B, Amundadottir L, Stolzenberg-Solomon R, Trichopoulou A, Onland-Moret NC, Lund E, Duell EJ, Canzian F, Severi G, Overvad K, Gunter MJ, Tumino R, Svenson U, van Rij A, Baas AF, Bown MJ, Samani NJ, van t'Hof FNG, Tromp G, Jones GT, Kuivaniemi H, Elmore JR, Johansson M, Mckay J, Scelo G, Carreras-Torres R, Gaborieau V, Brennan P, Bracci PM, Neale RE, Olson SH, Gallinger S, Li D, Petersen GM, Risch HA, Klein AP, Han J, Abnet CC, Freedman ND, Taylor PR, Maris JM, Aben KK, Kiemeney LA, Vermeulen SH, Wiencke JK, Walsh KM, Wrensch M, Rice T, Turnbull C, Litchfield K, Paternoster L, Standl M, Abecasis GR, SanGiovanni JP, Li Y, Mijatovic V, Sapkota Y, Low SK, Zondervan KT, Montgomery GW, Nyholt DR, van Heel DA, Hunt K, Arking DE, Ashar FN, Sotoodehnia N, Woo D, Rosand J, Comeau ME, Brown WM, Silverman EK, Hokanson JE, Cho MH, Hui J, Ferreira MA, Thompson PJ, Morrison AC, Felix JF, Smith NL, Christiano AM, Petukhova L, Betz RC, Fan X, Zhang X, Zhu C, Langefeld CD, Thompson SD, Wang F, Lin X, Schwartz DA, Fingerlin T, Rotter JI, Cotch MF, Jensen RA, Munz M, Dommisch H, Schaefer AS, Han F, Ollila HM, Hillary RP, Albagha O, Ralston SH, Zeng C, Zheng W, Shu XO, Reis A, Uebe S, Hüffmeier U, Kawamura Y, Otowa T, Sasaki T, Hibberd ML, Davila S, Xie G, Siminovitch K, Bei JX, Zeng YX, Försti A, Chen B, Landi S, Franke A, Fischer A, Ellinghaus D, Flores C, Noth I, Ma SF, Foo JN, Liu J, Kim JW, Cox DG, Delattre O, Mirabeau O, Skibola CF, Tang CS, Garcia-Barcelo M, Chang KP, Su WH, Chang YS, Martin NG, Gordon S, Wade TD, Lee C, Kubo M, Cha PC, Nakamura Y, Levy D, Kimura M, Hwang SJ, Hunt S, Spector T, Soranzo N, Manichaikul AW, Barr RG, Kahali B, Speliotes E, Yerges-Armstrong LM, Cheng CY, Jonas JB, Wong TY, Fogh I, Lin K, Powell JF, Rice K, Relton CL, Martin RM, Davey Smith G
JAMA Oncol 2017 May 1;3(5):636-651. doi: 10.1001/jamaoncol.2016.5945. PMID: 28241208Free PMC Article

Recent systematic reviews

Shimazaki K, Kurokawa R, Franson A, Kurokawa M, Baba A, Bou-Maroun L, Kim J, Moritani T
J Neuroimaging 2023 May-Jun;33(3):359-367. Epub 2023 Feb 20 doi: 10.1111/jon.13095. PMID: 36806312
Liu Y, Eaton ED, Wills TE, McCann SK, Antonic A, Howells DW
Transl Stroke Res 2018 Dec;9(6):564-574. Epub 2018 Mar 23 doi: 10.1007/s12975-018-0620-4. PMID: 29572690Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...