Monogenic diseases overlapping with VACTERL association
| Syndrome | OMIM | Locus | Gene | Vertebral anomalies | Overlap malformations | Characteristic features beyond VACTERL association | Reference |
|---|---|---|---|---|---|---|---|
| Fanconi anaemia with VACTERL-H | 227650; 300514 | 16q24; Xp22 | FANCA; FANCB,etc.* | Same phenotype with VACTERL but lower frequency | V, A, C TE, R, L | Haematological anomalies; pigmentary changes; hydrocephalus | Holden et al13 |
| Alagille syndrome | 118450 | 20p12; 1p12-p11 | JAG1; NOTCH2 | Mostly butterfly vertebra, occasionally hemivertebrae, fusion of vertebrae | V, C, R | Jaundice with conjugated hyperbilirubinemia; dysmorphic facies; posterior embryotoxon and retinal pigmentary changes | Turnpenny and Ellard14 |
| Basal cell nevus syndrome | 109400 | 9q22; 1p32; 10q24-q25 | PTCH1; PTCH2; SUFU | Multiple fusion of vertebral bodies and ribs | V, L | Odontogenic keratocysts of the jaw; palmar or plantar pits; bilamellar calcification of the falx cerebri; basal cell tumours | Oostra and Maas;15 Pino et al16 |
| Baller–Gerold syndromes | 218600 | 8q24 | RECQL4 | Rib fusion and flat vertebrae | V, A, C, R, L | Craniosynostosis; microcephaly | Murthy et al17 |
| DiGeorge syndrome (22q11.2 deletion syndrome) | 188400 | 22q11 | TBX1 | Hemivertebrae | V, C, R, L | Thymic abnormality;conotruncal cardiac anomaly; facial dysmorphism; hypocalcaemia | Tsirikos et al;18 Maggadottir and Sullivan19 |
| Feingold syndrome | 164280 | 2p23-24 | N-MYC | Absence of the fifth sacral vertebra and fusion of C5–C7in a case | V, C, TE, R, L | Microcephaly; brachymesophalangy | Celli et al20 |
| McKusick–Kaufman syndrome | 236700 | 20p12 | MKKS | Vertebral anomalies in one case | V, C, L | Hydrometrocolpos; gastrointestinal malformations | Knowles et al21 |
| CHARGE syndrome | 214800 | 8q12 | CHD7 | Idiopathic scoliosis without vertebral anomalies | C, TE, R | Coloboma; choanal atresia/stenosis;hypoplasia/aplasia of semicircular, etc. | Hsu et al;22 Verloes23 |
| Pallister–Hall syndrome | 146510 | 7p14.1 | GLI3 | NA | A, C, R, L | Hypothalamic hamartoma; bifid epiglottis; craniofacial abnormalities | Demurger et al24 |
| Townes–Brocks syndrome | 107480 | 16q21.1 | SALL1 | NA | A, C, R, L | Dysplastic ears with hearing impairment; intellectual disability | Sudo et al25 |
| Holt–Oram syndrome | 142900 | 12q24 | TBX5 | NA | C, L | NA | Goldfarb and Wall201426 |
| Hemifacial microsomia (OAVS) | 164210 | 14q32 | NA | Hemivertebrae, fusion of vertebrae | V, C | Craniofacial anomalies; central nervous system defects: visual and hearing impairment | Beleza-Meireles et al27 |
| TAR syndrome | 274000 | 1q21 | RBM8ANA | NA | C, R, L | Thrombocytopenia | Tassanoet al28 |
*Numbers of genes been implicated in the pathogenesis associated with Fanconi anaemia.29
A, anal atresia; C, cardiac malformations; CHARGE, Coloboma, Heart anomaly, Atresia of choanae, Retardation of mental and somatic development, Genital hypoplasia, Ear abnormalities; L, limb abnormalities; NA, not available; OAVS, oculo-auriculo-vertebral spectrum; R, renal anomalies; TAR, thrombocytopenia-absent radius; TE, tracheo-oesophageal fistula; V, vertebral anomalies; VACTERL, vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheo-oesophageal fistula (TE), renal dysplasia (R) and limb abnormalities (L); VACTERL-H, VACTERL association with hydrocephalus.