IllnessPrenatal VATER/VACTERL association, differential diagnosis

NGS +

[Sanger]

Patients with VACTERL association (vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula, renal and limb anomalies) typically have at least 3 of these characteristic features postnatally. Affected individuals may have additional symptoms besides VACTERL symptoms. Vertebral defects are seen in 60-80% of individuals with VACTERL association, including fused vertebrae, missing or additional vertebrae. 60-90% of these patients suufer(ed) from anal stenosis or atresia, sometimes along with urogenital malformations. Cardiac defects occur in 40-80% of patients, ranging in severity from life-threatening to subtle. Tracheoesophageal fistulas are present in 50-80% of affected individuals. Renal abnormalities occur in 50-80%, e.g., unilateral or bilateral renal aplasia or maldeveloped kidneys with impaired function. Limb abnormalities are seen in 40-50% of patients. These abnormalities often include absent or missing thumbs or forearms and hands. Some of the features of the VACTERL association may be minimally expressed and therefore these are not recognized until later in childhood or adulthood. Most cases occur sporadically. A few affected individuals have family members with only 1-2 features. In these families, a clear pattern of inheritance is often absent. Several genetic and environmental factors likely play a role in determining the risk for or expression of this disorder.

Although the spectrum of clinical symptoms determined by ultrasound in prenatal VACTERL association is naturally less extensively studied, the proportions are similar to those of postnatal VACTERL distribution: Spinal defects (>40%), anal atresia ( ̴30%), cardiac defects (>70%), tracheoesophageal fistulae ( ̴30%), renal malformations (>60%), limb malformations ( ̴40%), 3 or more severe abnormalities (>90%).

Reference: https://www.ncbi.nlm.nih.gov/books/NBK5192/

• Sympt.: VATER = Vertebral defefects [V], Anal atresia [A]...
• Sympt.: VACTERL = VATER + Cardiac malformations + Limb anomalies
• ...Tracheoesophageal fistula [T]- Esophageal atresia [E], Radial/Renal dysplasia [R]
• CHARGE syndrome: Coloboma [C], Heart defect [H], Atresia choanae [A] ...
• ... Retarded growth + development [R], Genital hypoplasia [G], Ear anomalies/deafness [E]
• Allelic: Aplasia of lacrimal + salivary glands (FGF19)
• Allelic: Congenital heart defects, nonsyndromic, 1, XL (ZIC3)
• Allelic: Duane-radial ray syndrome (SALL4)
• Allelic: Hand-foot-uterus syndrome (HOXA13)
• Allelic: Heterotaxy, visceral, 1, XL (ZIC3)
• Allelic: Hydroxykynureninuria (KYNU)
• Allelic: Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Allelic: Leukemia, acute promyelocytic (RARA)
• Allelic: Polydactyly, postaxial, types A1 + B (GLI3)
• Allelic: Polydactyly, preaxial, type IV (GLI3)
• Allelic: Retinitis pigmentosa 71 (IFT172)
• Allelic: Schizencephaly (SHH)
• Allelic: Single median maxillary central incisor (SHH)
• Alveolar capillary dysplasia with misalignment of pulmonary veins (FOXF1)
• Amelia, posterior, with pelvic + pulmonary hypoplasia syndrome (TBX4)
• Bardet-Biedl syndrome 20 (IFT172)
• CHARGE syndrome (VHD7)
• COACH syndrome 2 (CC2D2A)
• Caudal duplication anomaly (AXIN1)
• Cranioectodermal dysplasia 2 (WDR35)
• Cryptophthalmos, unilateral or bilateral, isolated (FREM2)
• Culler-Jones syndrome (GLI2)
• Fanconi anemia, complementation group A (FANCA)
• Fanconi anemia, complementation group B (FANCB)
• Fanconi anemia, complementation group C (FANCC)
• Fanconi anemia, complementation group D2 (FANCD2)
• Fanconi anemia, complementation group E (FANCE)
• Fanconi anemia, complementation group F (FANCF)
• Feingold syndrome 1 (MYCN)
• Fraser syndrome 2 (FREM2)
• Greig cephalopolysyndactyly syndrome (GLI3)
• Guttmacher syndrome (HOXA13)
• Holoprosencephaly 3 (SHH)
• Holoprosencephaly 9 (GLI2)
• Holt-Oram syndrome (TBX5)
• Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
• IVIC syndrome (SALL4)
• Ischiocoxopodopatellar syndrome with/-out pulmonary arterial hypertension (TBX4)
• Joubert syndrome 27 (B9D1)
• Joubert syndrome 9 (CC2D2A)
• LADD syndrome (FGF10)
• Mandibulofacial dysostosis, Guion-Almeida type (EFTUD2)
• Meckel syndrome 6 (CC2D2A)
• Meckel syndrome 9 (B9D1)
• Microphthalmia with coloboma 5 (SHH)
• Microphthalmia, syndromic 12 (RARB)
• Microphthalmia, syndromic 3 (SOX2)
• Mitchell-Riley s. [cong. diab., pancr. hypopl., intest. atresia, gallbladder a-/hypoplasia] (RFX6)
• Opitz GBBB syndrome, type I (MID1)
• Optic nerve hypoplasia + abnormalities of the central nervous system (SOX2)
• Pallister-Hall syndrome (GLI3)
• Pancreatic agenesis 2 (PTF1A)
• Pancreatic and cerebellar agenesis (PTF1A)
• Robinow syndrome, AD 1 (WNT5A)
• Short-rib thoracic dysplasia 10 with/-out polydactyly (IFT172)
• Short-rib thoracic dysplasia 3 with/-out polydactyly (DYNC2H1)
• Short-rib thoracic dysplasia 7 with/-out polydactyly (WDR35)
• Sifrim-Hitz-Weiss syndrome (CHD4)
• Townes-Brocks branchiootorenal-like syndrome (SALL1)
• Townes-Brocks syndrome 1 (SALL1)
• Townes-Brocks syndrome 2 (DACT1)
• Ulnar-mammary syndrome (TBX3)
• VACTERL association, XL (ZIC3)
• Verheij syndrome (PUF60)
• Vertebral, cardiac, renal + limb defects syndrome 1 (HAAO)
• Vertebral, cardiac, renal + limb defects syndrome 2 (KYNU)