CHARGE syndrome: report of 47 cases and review.

The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.

[1]  R. Pauli,et al.  Cranial nerve abnormalities in CHARGE association. , 1993, American journal of medical genetics.

[2]  L. Kaplan.  Choanal atresia and its associated anomalies. Further support for the CHARGE Association. , 1985, International journal of pediatric otorhinolaryngology.

[3]  S. Podos,et al.  Ocular colobomata, cardiac defect, and other anomalies: a study of seven cases including two sibs. , 1975, Journal of medical genetics.

[4]  L. Heitlinger,et al.  Nutritional assessment of children with short-bowel syndrome receiving home parenteral nutrition. , 1987, American journal of diseases of children.

[5]  R. Poland.  Bilirubin toxicity model questioned. , 1982, Pediatrics.

[6]  R. Wyse,et al.  CHARGE and esophageal atresia. , 1992, Journal of pediatric surgery.

[7]  M. Kirby,et al.  Role of Neural Crest in Congenital Heart Disease , 1990, Circulation.

[8]  S. Daniels,et al.  Spectrum of congenital heart disease in CHARGE association. , 1987, The Journal of pediatrics.

[9]  T. France,et al.  Ocular findings in CHARGE syndrome. Six case reports and a review. , 1988, Ophthalmology.

[10]  J. Wiley,et al.  Agonadism in a 46,XY patient with CHARGE association. , 1992, American journal of medical genetics.

[11]  J. Thelin,et al.  CHARGE syndrome. Part II. Hearing loss. , 1986, International journal of pediatric otorhinolaryngology.

[12]  R. Pagon,et al.  Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. , 1981, The Journal of pediatrics.

[13]  A. Munnich,et al.  Increased paternal age in CHARGE association , 1996, Clinical genetics.

[14]  M. Kliewer,et al.  Antenatal ultrasonographic findings in the CHARGE association. , 1994, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[15]  B. Korf,et al.  CHARGE association in a child with de novo inverted duplication (14)(q22-->q24.3). , 1995, American journal of medical genetics.

[16]  M. Warburg.  Ocular coloboma and multiple congenital anomalies: The CHARGE association , 1983 .

[17]  D. Friendly,et al.  Hypopituitarism and the CHARGE association. , 1983, The Journal of pediatrics.

[18]  B. Hall.  Choanal atresia and associated multiple anomalies. , 1979, The Journal of pediatrics.

[19]  R. Erickson,et al.  Re-evaluation of new X-linked syndrome for evidence of CHARGE syndrome or association. , 1989, American journal of medical genetics.

[20]  J A Hurst,et al.  Unknown syndrome: congenital heart disease, choanal stenosis, short stature, developmental delay, and dysmorphic facial features in a brother and sister. , 1989, Journal of Medical Genetics.

[21]  D. Taylor,et al.  The eye in the CHARGE association. , 1990, The British journal of ophthalmology.

[22]  R. Wyse,et al.  Ear-nose-throat abnormalities in the CHARGE association. , 1993, Archives of otolaryngology--head & neck surgery.

[23]  J. Hurst,et al.  Balanced t(6;8)(6p8p;6q8q) and the CHARGE association. , 1991, Journal of medical genetics.

[24]  M. Miller,et al.  Familial CHARGE syndrome: clinical report with autopsy findings. , 1987, American journal of medical genetics.

[25]  J. Guyot,et al.  The temporal bone anomaly in CHARGE association. , 1987, Archives of otolaryngology--head & neck surgery.

[26]  S. Balcı,et al.  Familial short rib syndrome, type Beemer, with pyloric stenosis and short intestine, one case diagnosed prenatally , 1991, Clinical genetics.

[27]  E. Zackai,et al.  The pattern of cardiovascular malformation in the CHARGE association. , 1987, American journal of diseases of children.

[28]  N. L. Le Douarin,et al.  Head morphogenesis in embryonic avian chimeras: evidence for a segmental pattern in the ectoderm corresponding to the neuromeres. , 1990, Development.

[29]  R. Wyse,et al.  Who's in CHARGE? Multidisciplinary management of patients with CHARGE association. , 1990, Archives of disease in childhood.

[30]  J. Manzione,et al.  Anatomic Findings and Management of Choanal Atresia and the Charge Association , 1988, The Annals of otology, rhinology, and laryngology.

[31]  C. G. Wright,et al.  Auditory and Temporal Bone Abnormalities in Charge Association , 1986, The Annals of otology, rhinology, and laryngology.

[32]  D. Lacombe.  Facial palsy and cranial nerve abnormalities in CHARGE association. , 1994, American journal of medical genetics.

[33]  L. Bergstrom,et al.  Posterior choanal atresia: A syndromal disorder , 1984, The Laryngoscope.

[34]  A. Munnich,et al.  Features of DiGeorge syndrome and CHARGE association in five patients. , 1997, Journal of medical genetics.

[35]  M. Baraitser,et al.  A reappraisal of the CHARGE association. , 1988, Journal of medical genetics.

[36]  R. Barrio,et al.  The CHARGE association and athyreosis. , 1991, Journal of medical genetics.

[37]  R. Tenconi,et al.  Apparent CHARGE association and chromosome anomaly: chance or contiguous gene syndrome. , 1991, American journal of medical genetics.

[38]  E. Goldson,et al.  The CHARGE association. How well can they do? , 1986, American journal of diseases of children.

[39]  J. Graham,et al.  Pathologic features of the CHARGE association: support for involvement of the neural crest. , 1985, Teratology.

[40]  P. Meinecke,et al.  Limb anomalies in the CHARGE association. , 1989, Journal of medical genetics.

[41]  J. Thelin,et al.  CHARGE syndrome. Part I. External ear anomalies. , 1986, International journal of pediatric otorhinolaryngology.

[42]  J W Thelin,et al.  Dominant CHARGE association. , 1985, Ophthalmic paediatrics and genetics.

[43]  J. Graham,et al.  Central nervous system malformations in the CHARGE association. , 1990, American journal of medical genetics.

[44]  G. Healy,et al.  Airway complications in CHARGE association. , 1990, Archives of otolaryngology--head & neck surgery.

[45]  K. Grundfast,et al.  Otorhinolaryngic Manifestations of CHARGE Association , 1985, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[46]  M. Lubinsky.  Properties of associations: identity, nature, and clinical criteria, with a commentary on why CHARGE and Goldenhar are not associations. , 1994, American journal of medical genetics.