Quantitative Analysis of Limb Anomalies in CHARGE Syndrome: Correlation With Diagnosis and Characteristic CHARGE Anomalies

Katharine E. Brock, Michelle A. Mathiason, Brenda L. Rooney, Marc S. Williams

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9 Scopus citations


CHARGE syndrome was initially not thought to involve the limb. Several subsequent reports have shown that limb anomalies are not uncommon. To date, there have been no quantitative studies of limb anomalies in CHARGE syndrome. This study was designed to answer several questions: Do CHARGE patients with limb anomalies represent a subgroup within CHARGE syndrome? Are there correlations between certain CHARGE syndrome anomalies and limb anomalies? Are there differences between the two genders and associated limb anomalies? Are certain types of limb anomalies seen with increased frequency in CHARGE syndrome? All described patients were categorized utilizing the AI/GEN Model 2 Criteria proposed by Mitchell [1985a: J Med Syst 9:425-435]. Patients with chromosomal anomalies or familial CHARGE were excluded, as were patients with inadequate clinical descriptions, and patients in large series where individual characteristics could not be ascertained. Multivariate analysis was performed. One hundred seventy two patients with definite or probable CHARGE syndrome were analyzed. Sixty-four (37.2%) of these patients have at least one limb anomaly. Significant positive associations were seen between limb anomalies and ocular coloboma, urinary tract malformations, and genital anomalies. These associations were not significant when the definite or probable patients were analyzed separately, with the exception of genital anomalies in definite CHARGE. Gender differences were also identified. Females with tracheoesophageal fistula/esophageal atresia, or genital anomalies were more likely to have limb anomalies, while some female subgroups had positive associations between urinary tract malformations, or choanal atresia and limb anomalies. Negative associations were also seen with sensorineural hearing loss and facial paralysis. In contrast, males showed a positive association between coloboma and limb anomalies, while subgroup analysis identified positive associations with DiGeorge sequence or genital anomalies and limb anomalies. Limb anomalies are present in just over one-third of CHARGE syndrome patients. Limb anomalies are seen more frequently in association with certain CHARGE anomalies, and these associations show gender differences. There is not a common limb anomaly seen in CHARGE syndrome.

Original languageEnglish (US)
Pages (from-to)111-121
Number of pages11
JournalAmerican Journal of Medical Genetics
Volume123 A
Issue number1
StatePublished - Nov 15 2003
Externally publishedYes


  • CHARGE syndrome
  • Limb anomalies
  • Multiple congenital anomalies


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