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International Journal of Pediatric Endocrinology

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Open Access 01-12-2011 | Case report

Unique phenotype in a patient with CHARGE syndrome

Authors: Shobhit Jain, Hyung-Goo Kim, Felicitas Lacbawan, Irene Meliciani, Wolfgang Wenzel, Ingo Kurth, Josefina Sharma, Morris Schoeneman, Svetlana Ten, Lawrence C Layman, Elka Jacobson-Dickman

Published in: International Journal of Pediatric Endocrinology | Issue 1/2011

Abstract

CHARGE is a phenotypically heterogeneous autosomal dominant disorder recognized as a cohesive syndrome since the identification of CHD7 as a genetic etiology. Classic features include: Coloboma, Heart defects, Atresia choanae, Retarded growth and development, Genitourinary abnormalities, and Ear anomalies and/or deafness. With greater accessibility to genetic analysis, a wider spectrum of features are emerging, and overlap with disorders such as DiGeorge syndrome, Kallmann syndrome, and Hypoparathyroidism Sensorineural Deafness and Renal Disease syndrome, is increasingly evident. We present a patient with a unique manifestation of CHARGE syndrome, including primary hypoparathyroidism and a limb anomaly; to our knowledge, he is also the first CHARGE subject reported with bilateral multicystic dysplastic kidneys. Furthermore, with structural modeling and murine expression studies, we characterize a putative CHD7 G744S missense mutation. Our report continues to expand the CHARGE phenotype and highlights that stringent fulfillment of conventional criteria should not strictly guide genetic analysis.

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Jongmans MC, Admiraal RJ, van der Donk KP, Vissers LE, Baas AF, Kapusta L, van Hagen JM, Donnai D, de Ravel TJ, Veltman JA, Geurts van Kessel A, De Vries BB, Brunner HG, Hoefsloot LH, van Ravenswaaij CM: CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. Journal of medical genetics. 2006, 43 (4): 306-14.PubMedCentralCrossRefPubMed

Lalani SR, Safiullah AM, Fernbach SD, Harutyunyan KG, Thaller C, Peterson LE, McPherson JD, Gibbs RA, White LD, Hefner M, Davenport SL, Graham JM, Bacino CA, Glass NL, Towbin JA, Craigen WJ, Neish SR, Lin AE, Belmont JW: Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. American journal of human genetics. 2006, 78 (2): 303-14. 10.1086/500273.PubMedCentralCrossRefPubMed

Jongmans MC, Hoefsloot LH, van der Donk KP, Admiraal RJ, Magee A, van de Laar I, Hendriks Y, Verheij JB, Walpole I, Brunner HG, van Ravenswaaij CM: Familial CHARGE syndrome and the CHD7 gene: a recurrent missense mutation, intrafamilial recurrence and variability. American journal of medical genetics. 2008, 146A (1): 43-50. 10.1002/ajmg.a.31921.CrossRefPubMed

Hall BD: Choanal atresia and associated multiple anomalies. The Journal of pediatrics. 1979, 95 (3): 395-8. 10.1016/S0022-3476(79)80513-2.CrossRefPubMed

Hittner HM, Hirsch NJ, Kreh GM, Rudolph AJ: Colobomatous microphthalmia, heart disease, hearing loss, and mental retardation--a syndrome. Journal of pediatric ophthalmology and strabismus. 1979, 16 (2): 122-8.PubMed

Pagon RA, Graham JM, Zonana J, Yong SL: Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. The Journal of pediatrics. 1981, 99 (2): 223-7. 10.1016/S0022-3476(81)80454-4.CrossRefPubMed

Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, van der Vliet WA, Huys EH, de Jong PJ, Hamel BC, Schoenmakers EF, Brunner HG, Veltman JA, van Kessel AG: Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nature genetics. 2004, 36 (9): 955-7. 10.1038/ng1407.CrossRefPubMed

Sanka M, Tangsinmankong N, Loscalzo M, Sleasman JW, Dorsey MJ: Complete DiGeorge syndrome associated with CHD7 mutation. The Journal of allergy and clinical immunology. 2007, 120 (4): 952-4. 10.1016/j.jaci.2007.08.013.CrossRefPubMed

Wincent J, Holmberg E, Stromland K, Soller M, Mirzaei L, Djureinovic T, Robinson K, Anderlid B, Schoumans J: CHD7 mutation spectrum in 28 Swedish patients diagnosed with CHARGE syndrome. Clinical genetics. 2008, 74 (1): 31-8. 10.1111/j.1399-0004.2008.01014.x.CrossRefPubMed

10.

Zentner GE, Layman WS, Martin DM, Scacheri PC: Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome. American journal of medical genetics. 2010, 152A (3): 674-86. 10.1002/ajmg.a.33323.PubMedCentralCrossRefPubMed

11.

Sullivan KE: Chromosome 22q11.2 deletion syndrome: DiGeorge syndrome/velocardiofacial Syndrome. Immunology and allergy clinics of North America. 2008, 28 (2): 353-66. 10.1016/j.iac.2008.01.003.CrossRefPubMed

12.

Hasegawa T, Hasegawa Y, Aso T, Koto S, Nagai T, Tsuchiya Y: HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia) associated with del(10)(p13). American journal of medical genetics. 1997, 73 (4): 416-8. 10.1002/(SICI)1096-8628(19971231)73:4<416::AID-AJMG9>3.0.CO;2-L.CrossRefPubMed

13.

Van Esch H, Groenen P, Nesbit MA, Schuffenhauer S, Lichtner P, Vanderlinden G, Harding B, Beetz R, Bilous RW, Holdaway I, Shaw NJ, Fryns JP, Van de Ven W, Thakker RV, Devriendt K: GATA3 haplo-insufficiency causes human HDR syndrome. Nature. 2000, 406 (6794): 419-22. 10.1038/35019088.CrossRefPubMed

14.

Yonekura K, Maki-Yonekura S, Namba K: Complete atomic model of the bacterial flagellar filament by electron cryomicroscopy. Nature. 2003, 424 (6949): 643-50. 10.1038/nature01830.CrossRefPubMed

15.

Porollo A, Meller J: Prediction-based fingerprints of protein-protein interactions. Proteins. 2007, 66 (3): 630-45.CrossRefPubMed

16.

Ramensky V, Bork P, Sunyaev S: Human non-synonymous SNPs: server and survey. Nucleic acids research. 2002, 30 (17): 3894-900. 10.1093/nar/gkf493.PubMedCentralCrossRefPubMed

17.

Delmas V, Stokes DG, Perry RP: A mammalian DNA-binding protein that contains a chromodomain and an SNF2/SWI2-like helicase domain. Proceedings of the National Academy of Sciences of the United States of America. 1993, 90 (6): 2414-8. 10.1073/pnas.90.6.2414.PubMedCentralCrossRefPubMed

18.

Woodage T, Basrai MA, Baxevanis AD, Hieter P, Collins FS: Characterization of the CHD family of proteins. Proceedings of the National Academy of Sciences of the United States of America. 1997, 94 (21): 11472-7. 10.1073/pnas.94.21.11472.PubMedCentralCrossRefPubMed

19.

Eissenberg JC: Molecular biology of the chromo domain: an ancient chromatin module comes of age. Gene. 2001, 275 (1): 19-29. 10.1016/S0378-1119(01)00628-X.CrossRefPubMed

20.

Sanlaville D, Etchevers HC, Gonzales M, Martinovic J, Clement-Ziza M, Delezoide AL, Aubry MC, Pelet A, Chemouny S, Cruaud C, Audollent S, Esculpavit C, Goudefroye G, Ozilou C, Fredouille C, Joye N, Morichon-Delvallez N, Dumez Y, Weissenbach J, Munnich A, Amiel J, Encha-Razavi F, Lyonnet S, Vekemans M, Attié-Bitach T: Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development. Journal of medical genetics. 2006, 43 (3): 211-17.PubMedCentralCrossRefPubMed

21.

Layman WS, McEwen DP, Beyer LA, Lalani SR, Fernbach SD, Oh E, Swaroop A, Hegg CC, Raphael Y, Martens JR, Martin DM: Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome. Human molecular genetics. 2009, 18 (11): 1909-23. 10.1093/hmg/ddp112.PubMedCentralCrossRefPubMed

22.

Vuorela P, Ala-Mello S, Saloranta C, Penttinen M, Poyhonen M, Huoponen K, Borozdin W, Bausch B, Botzenhart EM, Wilhelm C, Kääriäinen H, Kohlhase J: Molecular analysis of the CHD7 gene in CHARGE syndrome: identification of 22 novel mutations and evidence for a low contribution of large CHD7 deletions. Genet Med. 2007, 9 (10): 690-4. 10.1097/GIM.0b013e318156e68e.CrossRefPubMed

23.

Mitchell AL, Dwyer A, Pitteloud N, Quinton R: Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory. Trends Endocrinol Metab. 2011

24.

Sykiotis GP, Plummer L, Hughes VA, Au M, Durrani S, Nayak-Young S, Dwyer AA, Quinton R, Hall JE, Gusella JF, Seminara SB, Crowley WF, Pitteloud N: Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. Proc Natl Acad Sci USA. 2010, 107 (34): 15140-4. 10.1073/pnas.1009622107.PubMedCentralCrossRefPubMed

25.

Pitteloud N, Quinton R, Pearce S, Raivio T, Acierno J, Dwyer A, Plummer L, Hughes V, Seminara S, Cheng YZ, Li WP, Maccoll G, Eliseenkova AV, Olsen SK, Ibrahimi OA, Hayes FJ, Boepple P, Hall JE, Bouloux P, Mohammadi M, Crowley W: Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic hypogonadism. J Clin Invest. 2007, 117 (2): 457-63. 10.1172/JCI29884.PubMedCentralCrossRefPubMed

26.

Kim HG, Kurth I, Lan F, Meliciani I, Wenzel W, Eom SH, Kang GB, Rosenberger G, Tekin M, Ozata M, Bick DP, Sherins RJ, Walker SL, Shi Y, Gusella JF, Layman LC: Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. American journal of human genetics. 2008, 83 (4): 511-9. 10.1016/j.ajhg.2008.09.005.PubMedCentralCrossRefPubMed

27.

Jongmans MC, van Ravenswaaij-Arts CM, Pitteloud N, Ogata T, Sato N, Claahsen-van der Grinten HL, van der Donk K, Seminara S, Bergman JE, Brunner HG, Crowley WF, Hoefsloot LH: CHD7 mutations in patients initially diagnosed with Kallmann syndrome--the clinical overlap with CHARGE syndrome. Clinical genetics. 2009, 75 (1): 65-71. 10.1111/j.1399-0004.2008.01107.x.PubMedCentralCrossRefPubMed

28.

Brock KE, Mathiason MA, Rooney BL, Williams MS: Quantitative analysis of limb anomalies in CHARGE syndrome: correlation with diagnosis and characteristic CHARGE anomalies. American journal of medical genetics. 2003, 123A (1): 111-21.CrossRefPubMed

29.

Prasad C, Quackenbush EJ, Whiteman D, Korf B: Limb anomalies in DiGeorge and CHARGE syndromes. American journal of medical genetics. 1997, 68 (2): 179-81. 10.1002/(SICI)1096-8628(19970120)68:2<179::AID-AJMG11>3.0.CO;2-R.CrossRefPubMed

30.

Van de Laar I, Dooijes D, Hoefsloot L, Simon M, Hoogeboom J, Devriendt K: Limb anomalies in patients with CHARGE syndrome: an expansion of the phenotype. American journal of medical genetics. 2007, 143A (22): 2712-5. 10.1002/ajmg.a.32008.CrossRefPubMed

31.

Alazami AM, Alzahrani F, Alkuraya FS: Expanding the "E" in CHARGE. American journal of medical genetics. 2008, 146A (14): 1890-2. 10.1002/ajmg.a.32376.CrossRefPubMed

32.

Sanlaville D, Verloes A: CHARGE syndrome: an update. Eur J Hum Genet. 2007, 15 (4): 389-99. 10.1038/sj.ejhg.5201778.CrossRefPubMed

33.

Ragan DC, Casale AJ, Rink RC, Cain MP, Weaver DD: Genitourinary anomalies in the CHARGE association. The Journal of urology. 1999, 161 (2): 622-5. 10.1016/S0022-5347(01)61984-0.CrossRefPubMed

34.

Arena S, Fazzari C, Scuderi MG, Implatini A, Villari D, Torre S, Arena F, Di Benedetto V: Molecular events involved in the morphogenesis of multicystic dysplastic kidney. Urologia internationalis. 2010, 85 (1): 106-11. 10.1159/000296285.CrossRefPubMed

35.

Prontera P, Sensi A, Pilu G, Baldi M, Baffico M, Bonasoni R: FGFR3 mutation in thanatophoric dysplasia type 1 with bilateral cystic renal dysplasia: coincidence or a new association?. Genetic counseling (Geneva, Switzerland). 2006, 17 (4): 407-12.

36.

Fletcher J, Hu M, Berman Y, Collins F, Grigg J, McIver M, Jüppner H, Alexander SI: Multicystic dysplastic kidney and variable phenotype in a family with a novel deletion mutation of PAX2. J Am Soc Nephrol. 2005, 16 (9): 2754-61. 10.1681/ASN.2005030239.CrossRefPubMed

37.

Tellier AL, Amiel J, Delezoide AL, Audollent S, Auge J, Esnault D, Encha-Razavi F, Munnich A, Lyonnet S, Vekemans M, Attié-Bitach T: Expression of the PAX2 gene in human embryos and exclusion in the CHARGE syndrome. American journal of medical genetics. 2000, 93 (2): 85-8. 10.1002/1096-8628(20000717)93:2<85::AID-AJMG1>3.0.CO;2-B.CrossRefPubMed

38.

39.

40.

Jyonouchi S, McDonald-McGinn DM, Bale S, Zackai EH, Sullivan KE: CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic features. Pediatrics. 2009, 123 (5): e871-7. 10.1542/peds.2008-3400.PubMedCentralCrossRefPubMed

41.

McDonald-McGinn DM, Tonnesen MK, Laufer-Cahana A, Finucane B, Driscoll DA, Emanuel BS: Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: cast a wide FISHing net!. Genet Med. 2001, 3 (1): 23-9. 10.1097/00125817-200101000-00006.CrossRefPubMed

Title: Unique phenotype in a patient with CHARGE syndrome
Authors: Shobhit Jain
Hyung-Goo Kim
Felicitas Lacbawan
Irene Meliciani
Wolfgang Wenzel
Ingo Kurth
Josefina Sharma
Morris Schoeneman
Svetlana Ten
Lawrence C Layman
Elka Jacobson-Dickman
Publication date: 01-12-2011
Publisher: BioMed Central
Published in: International Journal of Pediatric Endocrinology / Issue 1/2011
Electronic ISSN: 1687-9856
DOI: https://doi.org/10.1186/1687-9856-2011-11

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Unique phenotype in a patient with CHARGE syndrome

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