Neural Crest System - Abnormalities
|Embryology - 27 Feb 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Neuroblastoma
- 4 DiGeorge syndrome
- 5 Neurofibromatosis Type 1 (NF1)
- 6 Intestinal Aganglionosis
- 7 Tetralogy of Fallot
- 8 Treacher Collins syndrome
- 9 Melanoma
- 10 Self Assessment Questions
- 11 OMIM Database
- 12 References
- 13 Additional Images
- 14 External Links
- 15 Glossary Links
While the cells originate from the ectoderm layer, unlike the neural tube which "pinches off" from the surface ectoderm, the neural crest cells head off on migrations throughout the embryo forming a diverse range of cell types and contributions to different tissues.
This behaviour also means that failure of correct migration or differentiation can lead to a number of different abnormalities.
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Shi-Yu Yang, Michelle Beavan, Kai-Yin Chau, Jan-Willem Taanman, Anthony H V Schapira A Human Neural Crest Stem Cell-Derived Dopaminergic Neuronal Model Recapitulates Biochemical Abnormalities in GBA1 Mutation Carriers. Stem Cell Reports: 2017; PubMed 28216145
Linlea Armstrong, Maja Tarailo-Graovac, Graham Sinclair, Kimberly I Seath, Wyeth W Wasserman, Colin J Ross, Clara D M van Karnebeek A girl with developmental delay, ataxia, cranial nerve palsies, severe respiratory problems in infancy-Expanding NDST1 syndrome. Am. J. Med. Genet. A: 2017, 173(3);712-715 PubMed 28211985
C Seinturier, S Blaise, F Thony, J L Magne, G Pernod A femoral common vein aneurysm in a patient with neurofibromatosis syndrome type 1. Ann Vasc Surg: 2017; PubMed 28163183
A Hudson, M Macdonald, J N Friedman, K Blake CHARGE syndrome gastrointestinal involvement: from mouth to anus. Clin. Genet.: 2016; PubMed 28155231
A smaller recent infant cancer study (Tiwan, Medical Center Cancer Registry, 1995 - 2001) of 82 infants (40 males and 42 females, 12 neonates) showed neuroblastoma as the third most common infant cancer (12 infants 14.6%).
Changes in Chilhood Survival Rates - Neuroblastoma
|Cancer||Infant number (percentage)|
|acute leukemia||21 infants (25.6%; acute myeloid leukemia in 12, and acute lymphoblastic leukemia in 9)|
|brain tumor||9 (11.0%)|
|germ cell tumor||8 (9.8%)|
|soft tissue sarcoma||5 (rhabdomyosarcoma 1, fibrosarcoma 3, other sarcoma 1)|
Childhood Cancer Survival Rates table modified from: Childhood Cancer Survivor Study
See data from and another Italian study showed: "Age of less than 1 year at time of diagnosis was a favorable prognostic factor for neuroblastoma and ganglioneuroblastoma. The extent of disease at diagnosis was related to prognosis for neuroblastoma and ganglioneuroblastoma and other selected solid tumors."
Database Search: OMIM- Neuroblastoma (2006 - 242 search results)
Links: OMIM - Neuroblastoma
DiGeorge syndrome is the most frequent microdeletion syndrome in humans caused by a hemizygous deletion (1.5 to 3.0-Mb) of chromosome 22q11.2.
Velo-cardio-facial syndrome, Hypoplasia of thymus and parathyroids, third and fourth pharyngeal pouch syndrome.
Abnormalities: cardiovascular, thymic and parathyroid, craniofacial anomalies, renal anomalies, hypocalcemia and immunodeficiency.
Links: OMIM - Digeorge Syndrome |
References: Wurdak H, Ittner LM, Sommer L. DiGeorge syndrome and pharyngeal apparatus development. Bioessays. 2006 Nov;28(11):1078-86.
Neurofibromatosis Type 1 (NF1)
- Neurofibromatosis Type 1 (von Recklinghausen) occurs in 1 in 3,000 to 4,000 people with characteristic skin blemishes forming in early childhood.
- Multiple café-au-lait spots (flat skin patches darker than the surrounding area) appear in early childhood which increase in both size and number with age.
- tumors can develop along nerves in the skin, brain, and other parts of the body. In the iris of the eye, Lisch nodules (benign growths) also appear
- (French, café-au-lait = coffee with milk)
Links: OMIM - Neurofibromatosis Type 1 | Genetics Home Reference - Neurofibromatosis Type 1 | Nemours Foundation - Neurofibromatosis | Neurofibromatosis, Inc. (USA) | Atlas of Genetics and Cytogenetics in Oncology- Neurofibroma
Intestinal Aganglionosis, also known as Hirschsprung's Disease or Megacolon, is a lack of enteric nervous system (neural ganglia) in the intestinal tract responsible for gastric motility (peristalsis).
In general, its severity is dependent upon the amount of the GIT that lacks intrinsic ganglia, due to developmental lack of neural crest migration into those segments. (More? Gastrointestinal Tract - Abnormalities)
- Intestinal Aganglionosis, Hirschsprung's Disease or Megacolon
- lack of enteric nervous system (neural ganglia) in the intestinal tract responsible for gastric motility (peristalsis).
- severity is dependent upon the amount of the GIT that lacks intrinsic ganglia, due to developmental lack of neural crest migration into those segments.
- first indication in newborns is an absence of the first bowel movement, other symptoms include throwing up and intestinal infections.
- Clinically this is detected by one or more tests (barium enema and x ray, manometry or biopsy) and can currently only be treated by surgery. A temoporary ostomy (Colostomy or Ileostomy) with a stoma is carried out prior to a more permanent pull-through surgery.
|Short section of the colon without smooth muscle neural ganglia||Longer section without ganglia|
The first indication in newborns is an absence of the first bowel movement, other symptoms include throwing up and intestinal infections. Clinically this is detected by one or more tests (barium enema and x ray, manometry or biopsy) and can currently only be treated by surgery. A temoporary ostomy (Colostomy or Ileostomy) with a stoma is carried out prior to a more permanent pull-through surgery.
Congenital failure of autonomic control describes the occasional association with congenital central hypoventilation syndrome (CCHS, Ondine's curse or Haddad Syndrome) perhaps correlating with a failure of neural crest associated with the respiratory system. This condition is a decrease in respiration (hypoventilation) usually during sleep and an insensitivity to stimuli which should increase respiration (hypercarbia and hypoxia). Recent CCHS research has also identified Paired-like Homeobox 2B (PHOX2B) gene mutations associated with this disorder.
Search PubMed: hirschprung's+disease
Tetralogy of Fallot
Cardiac abnormality possibly stemming from abnormal neural crest migration. Named after Etienne-Louis Arthur Fallot (1888) who described it as "la maladie blue".
Treacher Collins syndrome
(TCS) A genetic developmental abnormality results from autosomal dominant mutations of the gene TCOF1 encoding the protein Treacle, identified in 2006. The syndrome is characterized by hypoplasia of the facial bones, cleft palate, and middle and external ear defects. These defects may relate to the effects on neural crest migration.
In Australia each year 8,800 people are diagnosed with melanoma, and almost 1000 people die (Data, Cancer Council Australia).
Two different findings on the reprogramming of melanoma cells, which have a neural crest origin, when transplanted between species into embryos.
Kulesa PM, Kasemeier-Kulesa JC, Teddy JM, Margaryan NV, Seftor EA, Seftor RE, Hendrix MJ. Reprogramming metastatic melanoma cells to assume a neural crest cell-like phenotype in an embryonic microenvironment. Proc Natl Acad Sci U S A. 2006 Feb 27; [Epub ahead of print]
Lee LM, Seftor EA, Bonde G, Cornell RA, Hendrix MJ. The fate of human malignant melanoma cells transplanted into zebrafish embryos: assessment of migration and cell division in the absence of tumor formation. Dev Dyn. 2005 Aug;233(4):1560-70.
Self Assessment Questions
Online Mendelian Inheritence in Man Database. OMIM
Internet Search OMIM database with the keyword "neural crest" or the above abnormality names.
OMIM Sample Entries
Neural Crest disease entries from 74 entries found (1999 search), using "neural crest"
*193500 WAARDENBURG SYNDROME, TYPE I; WS1
*162200 NEUROFIBROMATOSIS, TYPE I; NF1
*188400 DIGEORGE SYNDROME; DGS
#171400 MULTIPLE ENDOCRINE NEOPLASIA, TYPE II; MEN2#277580 WAARDENBURG-SHAH SYNDROME600501 ABCD SYNDROME*256700 NEUROBLASTOMA#142623 HIRSCHSPRUNG DISEASE#162300 MULTIPLE ENDOCRINE NEOPLASIA, TYPE IIB; MEN2B#130650 BECKWITH-WIEDEMANN SYNDROME; BWS164210 OCULOAURICULOVERTEBRAL DYSPLASIA#171300 PHEOCHROMOCYTOMA#176270 PRADER-WILLI SYNDROME; PWS#193510 WAARDENBURG SYNDROME, TYPE IIA; WS2A214800 CHOANAL ATRESIA, POSTERIOR; PCA*600594 DIGEORGE CRITICAL REGION GENE 2249400 MELANOSIS, NEUROCUTANEOUS*155735 MELANOMA ADHESION MOLECULE; MCAM217100 CONSTRICTING BANDS, CONGENITAL#146150 HYPOMELANOSIS OF ITO; HMI#137600 IRIDOGONIODYSGENESIS, TYPE 2; IRID2#188550 THYROID CARCINOMA, PAPILLARY*601499 RIEGER SYNDROME, TYPE 2; RIEG2#601631 IRIDOGONIODYSGENESIS, TYPE 1; IRID1*601654 EYES ABSENT 2; EYA2#118200 CHARCOT-MARIE-TOOTH DISEASE, TYPE 1B; CMT1B#106200 ANIRIDIA; AN1*602942 NEUROBLASTOMA STAGE 4S GENE603807 PETERS ANOMALY WITH CATARACT
- Elly Sau-Wai Ngan, Maria-Mercè Garcia-Barceló, Benjamin Hon-Kei Yip, Hiu-Ching Poon, Sin-Ting Lau, Carmen Ka-Man Kwok, Eric Sat, Mai-Har Sham, Kenneth Kak-Yuen Wong, Brandon J Wainwright, Stacey S Cherny, Chi-Chung Hui, Pak Chung Sham, Vincent Chi-Hang Lui, Paul Kwong-Hang Tam Hedgehog/Notch-induced premature gliogenesis represents a new disease mechanism for Hirschsprung disease in mice and humans. J. Clin. Invest.: 2011, 121(9);3467-78 PubMed 21841314
- Frances A High, Maozhen Zhang, Aaron Proweller, Lili Tu, Michael S Parmacek, Warren S Pear, Jonathan A Epstein An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J. Clin. Invest.: 2007, 117(2);353-63 PubMed 17273555
- Thomas J Hornyak The developmental biology of melanocytes and its application to understanding human congenital disorders of pigmentation. Adv Dermatol: 2006, 22;201-18 PubMed 17249303
- Elisa Dama, Guido Pastore, Maria Luisa Mosso, Milena Maria Maule, Luisa Zuccolo, Corrado Magnani, Franco Merletti Time trends and prognostic factors for survival from childhood cancer: a report from the Childhood Cancer Registry of Piedmont (Italy). Eur. J. Pediatr.: 2006, 165(4);240-9 PubMed 16411094
- Chao-Ping Yang, Iou-Jih Hung, Tang-Her Jaing, Lee-Yung Shih, Wan-Hui Chang Cancer in infants: a review of 82 cases. Pediatr Hematol Oncol: 2005, 22(6);463-81 PubMed 16169813
- Sofie De Schepper, Joachim Boucneau, Jo Lambert, Ludwine Messiaen, Jean-Marie Naeyaert Pigment cell-related manifestations in neurofibromatosis type 1: an overview. Pigment Cell Res.: 2005, 18(1);13-24 PubMed 15649148
- G D Croaker, E Shi, E Simpson, T Cartmill, D T Cass Congenital central hypoventilation syndrome and Hirschsprung's disease. Arch. Dis. Child.: 1998, 78(4);316-22 PubMed 9623393
Dwight R Cordero, Samantha Brugmann, Yvonne Chu, Ruchi Bajpai, Maryam Jame, Jill A Helms Cranial neural crest cells on the move: their roles in craniofacial development. Am. J. Med. Genet. A: 2011, 155A(2);270-9 PubMed 21271641
Yifei Liu, Andrew Xiao Epigenetic regulation in neural crest development. Birth Defects Res. Part A Clin. Mol. Teratol.: 2011, 91(8);788-96 PubMed 21618405
Paul A Trainor Craniofacial birth defects: The role of neural crest cells in the etiology and pathogenesis of Treacher Collins syndrome and the potential for prevention. Am. J. Med. Genet. A: 2010, 152A(12);2984-94 PubMed 20734335
Sunghoon Kim, Dai H Chung Pediatric solid malignancies: neuroblastoma and Wilms' tumor. Surg. Clin. North Am.: 2006, 86(2);469-87, xi PubMed 16580935
Chao-Ping Yang, Iou-Jih Hung, Tang-Her Jaing, Lee-Yung Shih, Wan-Hui Chang Cancer in infants: a review of 82 cases. Pediatr Hematol Oncol: 2005, 22(6);463-81 PubMed 16169813
G D Croaker, E Shi, E Simpson, T Cartmill, D T Cass Congenital central hypoventilation syndrome and Hirschsprung's disease. Arch. Dis. Child.: 1998, 78(4);316-22 PubMed 9623393
Raquel M Fernández, Marta Bleda, Berta Luzón-Toro, Luz García-Alonso, Stacey Arnold, Yunia Sribudiani, Claude Besmond, Francesca Lantieri, Betty Doan, Isabella Ceccherini, Stanislas Lyonnet, Robert Mw Hofstra, Aravinda Chakravarti, Guillermo Antiñolo, Joaquín Dopazo, Salud Borrego Pathways systematically associated to Hirschsprung's disease. Orphanet J Rare Dis: 2013, 8;187 PubMed 24289864
Elisa Dama, Guido Pastore, Maria Luisa Mosso, Milena Maria Maule, Luisa Zuccolo, Corrado Magnani, Franco Merletti Time trends and prognostic factors for survival from childhood cancer: a report from the Childhood Cancer Registry of Piedmont (Italy). Eur. J. Pediatr.: 2006, 165(4);240-9 PubMed 16411094
Ramesh Bajaj, Janine Smith, Delphine Trochet, John Pitkin, Robert Ouvrier, Nicole Graf, David Sillence, Martin Kluckow Congenital central hypoventilation syndrome and Hirschsprung's disease in an extremely preterm infant. Pediatrics: 2005, 115(6);e737-8 PubMed 15930201
Search April 2010 "Neural Crest Development" - All (4354) Review (843) Free Full Text (1621)
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Cite this page: Hill, M.A. 2017 Embryology Neural Crest System - Abnormalities. Retrieved February 27, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Neural_Crest_System_-_Abnormalities
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