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

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

[92–95]

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

[107–109]

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

[110–112]

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]