Neonatal Presentations of CHARGE Syndrome and VATER

geneticsCHARGE and VATER/VACTERLis usually sporadic. VACTERL-H is associated with apoorer prognosis in terms of survival and mental handicap.Overlap in the features associated withVACTERL-H and Fanconi anemia has been reported inseveral cases. Fanconi anemia is an autosomal recessivedisorder of DNA repair that leads to bone marrow failurein childhood and increased risk of malignancy; diagnosiscan be made using chromosomal breakage studies. In2005, Faivre and associates recommended chromosomalbreakage studies in cases of VACTERL-H and cases ofVACTERL in which the infant has dysmorphic features,skin pigmentation abnormalities, growth retardation, ormicrocephaly.Figure 3. Unilateral facial paralysis caused by an anomaly ofcranial nerve VII.ered, a CT scan of the temporal bones should beobtained to look for the suggestive middle and inner eardefects. The phenotype of 22q11 deletion syndrome isextremely variable; cardiac and renal anomalies are common,but anomalies in almost every organ system havebeen reported. Newborns who have a 22q11 deletionfrequently exhibit a distinctive facial appearance (laterallybuilt-up nasal bridge, small mouth, and short palpebralfissures), long fingers and toes, and possibly hypocalcemia.A fluorescence in situ hybridization study for22q11.2 deletion can be ordered to exclude this diagnosis.Townes–Brocks syndrome is characterized by thetriad of imperforate anus, dysplastic ears (with or withoutpits or tags and hearing loss), and thumb anomalies(triphalangeal thumbs, preaxial polydactyly, or hypoplasticthumbs). Affected infants also may have cardiac andrenal anomalies. This syndrome should be considereddue to the considerable overlap in phenotype. Clinicallyavailable genetic testing for Townes-Brocks syndromehas a detection rate of 70% to 75%.Multiple case reports have linked hydrocephalus withVACTERL association (VACTERL-H). VACTERL-Hmay represent a distinct syndrome because both autosomalrecessive and X-linked patterns of inheritancehave been described. In contrast, VACTERL associationGenetic TestingIf VACTERL association is considered, evaluations inthe neonatal period should include echocardiography,renal ultrasonography, radiographs of the spine, radiographsof the extremities if abnormalities are noted onexamination, and an ophthalmologic evaluation. Inaddition, high-resolution chromosome analysis and agenetics consultation should be obtained to excludeother genetic causes. The recurrence risk for parents andfor the individual is low, and the cause is unknown,although VACTERL is related to maternal diabetes inthe minority of cases.SummaryAlthough CHARGE syndrome and VACTERL associationhave several features in common, the distinctionbetween these two entities affects management, prognosis,and recurrence risk. In addition, a broad differentialdiagnosis needs to be considered in any patient whohas features of VACTERL association because this is adiagnosis of exclusion. A genetics evaluation should beconsidered for any newborn who has multiple congenitalanomalies.Suggested ReadingBlake KD, Devenport SL, Hall BD, et al. CHARGE association: anupdate and review for the primary pediatrician. Clin Pediatr.1998;37:159–173Blake KD, Hartshorne TS, Lawand C, Dailor AN, Thelin JW.Cranial nerve manifestations in CHARGE syndrome. Am J MedGenet. 2008;146A:585–592Blake KD, Prasad C. CHARGE syndrome. Orphanet J Rare Dis.2006;1:34Corsello G, Maresi E, Corrao AM, et al. VATER/VACTERLassociation: clinical variability and expanding phenotype includinglaryngeal stenosis. Am J Med Genet. 1992;44:813–815NeoReviews Vol.9 No.7 July 2008 e303Downloaded from http://neoreviews.aappublications.org by J Michael Coleman on August 12, 2010