Contiguous Gene Syndromes

1. Elaine Pereira, MD 2. Robert Marion, MD 1. Children’s Hospital at Montefiore, Bronx, NY 1. American Academy of Pediatrics: Health Care Supervision for Children with Williams Syndrome. Committee on Genetics. Pediatrics. 2001;107(5):1192–1204 [OpenUrl][1][Abstract/FREE Full Text][2] 2. 1. McCandless SE Clinical Report-Health Supervision for Children with Prader-Willi Syndrome. McCandless SE, Committee on Genetics. Pediatrics. 2011;127(1):195–204 [OpenUrl][3][Abstract/FREE Full Text][4] 3. 1. Cassidy SB, 2. Schwartz S, 3. Miller JL, 4. et al Prader-Willi Syndrome. Cassidy SB, Schwartz S, Miller JL, et al. Genet Med. 2012;14(1):10–26 [OpenUrl][5][CrossRef][6][PubMed][7] 4. 1. Kalsner L, 2. Chamberlain SJ Prader-Willi, Angelman, and 15q11-q13 Duplication Syndromes. Kalsner L, Chamberlain SJ. Pediatr Clin North Am. 2015;62(3):587–606 [OpenUrl][8][CrossRef][9][PubMed][10] The term contiguous gene syndromes describes a group of disorders in which a small deletion or duplication of genetic material that contains multiple genes causes a recognizable phenotype. Because microarrays capable of identifying microdeletions and microduplications have become a first-tier genetic test for patients with multiple congenital anomalies, intellectual disabilities, and autism spectrum disorder, more contiguous gene syndromes have been identified. Among the more common of these disorders are Prader-Willi syndrome (PWS), Angelman syndrome (AS), and Williams syndrome (WS). Another disorder, 22q11.2 deletion syndrome, was discussed in a recent In Brief. The accompanying Table is a compilation of known contiguous gene syndromes. View this table: Table. Clinically Recognizable Contiguous Gene Syndromes Although markedly different in phenotype, PWS and AS are both associated with chromosome 15 microdeletions. Prader-Willi syndrome has a prevalence of 1 in 10,000 to 30,000. In infancy, children with PWS have severe hypotonia, which leads to difficulty with feeding, failure to gain weight, and often the need for nasogastric or gastrostomy tube feeding. By 9 to 18 months, muscle tone begins to improve, and affected children are able to eat without assistance; in fact, they develop insatiable appetites. If untreated, this hyperphagia leads to multiple medical complications: obesity, type 2 diabetes mellitus, and obstructive sleep apnea. With age, facial features characteristic of PWS become more evident, including almond-shaped eyes, thin upper lip, downturned mouth, and narrow bifrontal head diameter. Generalized hypothalamic-hypopituitary axis insufficiency commonly occurs, affecting growth hormone secretion, thermoregulation, thyroid function, and respiratory control. Hypogonadism affects most patients, manifesting as cryptorchidism in males, incomplete pubertal development, and infertility. Behavioral and developmental problems include perseverant speech and obsessive compulsive behavior, with temper … [1]: {openurl}?query=rft.jtitle%253DPediatrics%26rft.stitle%253DPediatrics%26rft.aulast%253DCommittee%2Bon%2BGenetics%26rft.auinit1%253D%2B%26rft.volume%253D107%26rft.issue%253D5%26rft.spage%253D1192%26rft.epage%253D1204%26rft.atitle%253DHealth%2BCare%2BSupervision%2Bfor%2BChildren%2BWith%2BWilliams%2BSyndrome%26rft_id%253Dinfo%253Apmid%252F11331709%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=pediatrics&resid=107/5/1192&atom=%2Fpedsinreview%2F39%2F1%2F46.atom [3]: {openurl}?query=rft.jtitle%253DPediatrics%26rft_id%253Dinfo%253Adoi%252F10.1542%252Fpeds.2010-2820%26rft_id%253Dinfo%253Apmid%252F21187304%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [4]: /lookup/ijlink?linkType=ABST&journalCode=pediatrics&resid=127/1/195&atom=%2Fpedsinreview%2F39%2F1%2F46.atom [5]: {openurl}?query=rft.jtitle%253DGenetics%2Bin%2Bmedicine%2B%253A%2B%2Bofficial%2Bjournal%2Bof%2Bthe%2BAmerican%2BCollege%2Bof%2BMedical%2BGenetics%26rft.stitle%253DGenet%2BMed%26rft.aulast%253DCassidy%26rft.auinit1%253DS.%2BB.%26rft.volume%253D14%26rft.issue%253D1%26rft.spage%253D10%26rft.epage%253D26%26rft.atitle%253DPrader-Willi%2Bsyndrome.%26rft_id%253Dinfo%253Adoi%252F10.1038%252Fgim.0b013e31822bead0%26rft_id%253Dinfo%253Apmid%252F22237428%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [6]: /lookup/external-ref?access_num=10.1038/gim.0b013e31822bead0&link_type=DOI [7]: /lookup/external-ref?access_num=22237428&link_type=MED&atom=%2Fpedsinreview%2F39%2F1%2F46.atom [8]: {openurl}?query=rft.jtitle%253DPediatr%2BClin%2BNorth%2BAm%26rft.volume%253D62%26rft.spage%253D587%26rft_id%253Dinfo%253Adoi%252F10.1016%252Fj.pcl.2015.03.004%26rft_id%253Dinfo%253Apmid%252F26022164%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [9]: /lookup/external-ref?access_num=10.1016/j.pcl.2015.03.004&link_type=DOI [10]: /lookup/external-ref?access_num=26022164&link_type=MED&atom=%2Fpedsinreview%2F39%2F1%2F46.atom