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Table 1 Differential diagnosis: conditions with multiple features in common with VACTERL association.

From: VACTERL/VATER Association

Condition Features in common with VACTERL association Features distinct from VACTERL association Cause(s) Reference(s)
Alagille syndrome Vertebral anomalies, cardiac anomalies; may have renal anomalies Bile duct paucity and cholestasis, ophthalmologic anomalies (especially posterior embryotoxon), neurological anomalies, characteristic facial appearance Heterozygous mutations in JAG1, NOTCH2 [9295]
Baller-Gerold syndrome Radial anomalies, may also include anal anomalies Craniosynostosis, skin anomalies Heterozygous mutations in RECQL4 [33]
CHARGE syndrome Cardiac malformations, genitourinary anomalies; may also include TEF Colobomata, choanal atresia, neurocognitive and growth impairment, ear anomalies, cranial nerve dysfunction, characteristic facial features Heterozygous mutations in CHD7 [32, 96]
Currarino syndrome Sacral malformations, ARM Presacral mass Heterozygous mutations/
deletions of HLXB9
[97, 98]
22q11.2 deletion syndrome (also known by other names, such as DiGeorge syndrome or velocardio-facial syndrome) Cardiac malformations, renal anomalies, other VACTERL-type anomalies also reported Hypocalcemia, palatal anomalies, learning difficulties, immune dysfunction, neuropsychiatric disturbances, characteristic facial features, Deletion of one copy of chromosome 22q11.2 [99]
Fanconia anemia Virtually all features of VACTERL association may occur; radial anomalies are considered an especially key feature Hematologic anomalies, pigmentation anomalies Recessive or X-linked mutations in multiple genes; typically detected by chromosomal breakage studies [62, 63, 66, 100]
Feingold syndrome GI atresia, cardiac defects, renal anomalies Brachymesophalangy, toe syndactyly, microcephaly, cognitive impairment, characteristic facial appearance, Heterozygous mutations in MYCN [67, 101]
Fryns syndrome GI malformations, cardiac defects, GU anomalies Diaphragmatic defects, neurocognitive impairment, characteristic facial appearance, No well-characterized unifying causes [102]
Holt-Oram syndrome Cardiac malformations, limb malformations Cardiac conduction disease (also reported in VACTERL association) Heterozygous mutations in TBX5 [68, 103]
Müllerian duct aplasia, renal aplasia, and cervico-thoracic somite dysplasia (MURCS assoc-iation); also known as Mayer-Rokitansky- Küster-Hauser syndrome type II Vertebral anomalies, renal anomalies, GU anomalies and anorectal malformations; may also have cardiac and limb anomalies Syndactyly and hearing loss have been described Unknown; likely heterogeneous [104, 105]
Oculo-auriculo-vertebral syndrome Vertebral anomalies, cardiac abnormalities, limb abnormalities, urogenital anomalies Ear anomalies (microtia), hemifacial microsomia, neurocognitive impairment, facial clefts (also described in patients with VACTERL association) Unknown; likely heterogeneous [106]
Opitz G/BBB syndrome Anal anomalies, heart defects, TEF, hypospadias Hypertelorism, syndactyly X-linked form: heterozygous/
hemizygous mutations in MID1; autosomal dominant form: some cases due to deletion 22q11.2
Pallister-Hall syndrome Imperforate anus, renal anomalies, limb anomalies (postaxial polydactyly should serve as a clue for the Pallister-Hall syndrome) Hypothalamic hamartoma, bifid epiglottis (ranging to more severe types of clefts), nail hypoplasia Heterozygous mutations in GLI3 [110112]
Townes-Brocks syndrome Imperforate anus, thumb anomalies, renal anomalies, cardiac anomalies Dysplastic ears, hearing loss Heterozygous mutations in SALL1 [69, 113]
VACTERL-H All core component features Hydrocephalus Heterozygous mutations in PTEN, heterozygous/
hemizygous mutations in ZIC3; X-linked and recessive forms have been described
[64, 65, 90, 114]
  1. There are also many scattered case reports in the medical literature describing additional patients who have features observed in VACTERL association, but only the main overlapping conditions are described here.
  2. GI: gastrointestinal; GU: genitourinary; H:hydrocephalus; TEF: tracheo-esophageal fistula