vacterl ( vertebral defects , anal atresia , cardiovascular malformation , tracheo - esophageal fistula with esophageal atresia , radial / renal dysplasia and limb anomalies ) is a non - random and typically sporadic association of malformations in structures derived from the embryonic mesoderm . quan and smith first proposed this association , initially with the acronym of vater ( v , vertebral defects ; a , anal atresia ; te , tracheoesophageal fistula with esophageal atresia ; r , radial dysplasia ) . vacterl is an acronym for an expanded definition of the association that includes cardiac ( c ) and renal ( r ) malformations , and additional limb anomalies ( l ) other than radial dysplasia . vertebral anomalies , which usually consist of absent or dysplastic vertebrae , have been reported in 60 - 80% of patients . however , anal atresia detection by ultrasound has already been reported at 12 weeks of gestation . the most frequent cardiac malformations include ventricular septal defects , atrial defects and tetralogy of fallot . approximately 50 to 80% of patients present with tracheoesophageal fistula , which can be suspected in utero in the presence of polyhydramnios or absent gastric bubble . renal anomalies , which occur in up to 80% of cases , can include unilateral or bilateral renal agenesis , horseshoe kidney and cystic and/or dysplastic kidneys . although limb malformations were classically defined as radial anomalies , vacterl association currently encompasses other limb anomalies , as polydactyly , syndactyly and lower limb defects . genitourinary anomalies , although not considered one of the component features , are a subset of malformations frequently observed in vacterl association . genitourinary anomalies are more commonly observed in patients also affected by malformations of lower intestinal and renal systems , but may be present in patients without the referred anomalies . genitourinary defects described in patients with vacterl association include ambiguous genitalia , genitourinary fistula , cryptorchidism and hypospadias . defects in practically every organ system have been described in patients with vacterl and are considered additional criteria for this association : facial asymmetry , external ear malformation , lung lobation defects , among others . maternal diabetes , in utero exposures to estrogen/ progesterone , statins , doxorubicin and lead have been implicated as environmental risk factors for this association . mutations in sonic hedgehog pathway genes have been implicated in vacterl association . a mutation in the homebox d13 gene ( hoxd13 ) , most investigators consider the presence of at least three of the cardinal features as a condition for diagnosis . however , only 1% of cases present the full spectrum of anomalies . clinical presentation is diverse , ranging from mild cases undiagnosed until adulthood to severe cases that are obvious the prenatal or neonatal period . prenatal diagnosis is challenging considering many key features of this association are not easily detectable before birth . neonates with vacterl require significant surgical treatment and the quality of the care given to the newborn is crucial . despite treatment , prognosis is generally poor but largely depends on the extension of malformations . we report a rare case of vacterl association in which the characteristic defects were detected in the first trimester of pregnancy . vacterl ( vertebral defects , anal atresia , cardiovascular malformation , tracheo - esophageal fistula with esophageal atresia , radial / renal dysplasia and limb anomalies ) is a non - random and typically sporadic association of malformations in structures derived from the embryonic mesoderm . quan and smith first proposed this association , initially with the acronym of vater ( v , vertebral defects ; a , anal atresia ; te , tracheoesophageal fistula with esophageal atresia ; r , radial dysplasia ) . vacterl is an acronym for an expanded definition of the association that includes cardiac ( c ) and renal ( r ) malformations , and additional limb anomalies ( l ) other than radial dysplasia . vertebral anomalies , which usually consist of absent or dysplastic vertebrae , have been reported in 60 - 80% of patients . however , anal atresia detection by ultrasound has already been reported at 12 weeks of gestation . the most frequent cardiac malformations include ventricular septal defects , atrial defects and tetralogy of fallot . approximately 50 to 80% of patients present with tracheoesophageal fistula , which can be suspected in utero in the presence of polyhydramnios or absent gastric bubble . renal anomalies , which occur in up to 80% of cases , can include unilateral or bilateral renal agenesis , horseshoe kidney and cystic and/or dysplastic kidneys . although limb malformations were classically defined as radial anomalies , vacterl association currently encompasses other limb anomalies , as polydactyly , syndactyly and lower limb defects . genitourinary anomalies , although not considered one of the component features , are a subset of malformations frequently observed in vacterl association . genitourinary anomalies are more commonly observed in patients also affected by malformations of lower intestinal and renal systems , but may be present in patients without the referred anomalies . genitourinary defects described in patients with vacterl association include ambiguous genitalia , genitourinary fistula , cryptorchidism and hypospadias . defects in practically every organ system have been described in patients with vacterl and are considered additional criteria for this association : facial asymmetry , external ear malformation , lung lobation defects , among others . maternal diabetes , in utero exposures to estrogen/ progesterone , statins , doxorubicin and lead have been implicated as environmental risk factors for this association . mutations in sonic hedgehog pathway genes have been implicated in vacterl association . a mutation in the homebox d13 gene ( hoxd13 ) , most investigators consider the presence of at least three of the cardinal features as a condition for diagnosis . however , only 1% of cases present the full spectrum of anomalies . clinical presentation is diverse , ranging from mild cases undiagnosed until adulthood to severe cases that are obvious the prenatal or neonatal period . prenatal diagnosis is challenging considering many key features of this association are not easily detectable before birth . neonates with vacterl require significant surgical treatment and the quality of the care given to the newborn is crucial . despite treatment , prognosis is generally poor but largely depends on the extension of malformations . we report a rare case of vacterl association in which the characteristic defects were detected in the first trimester of pregnancy . a 20-year - old primigravid , caucasian woman was referred to our fetal medicine unit at 11 weeks gestation for first trimester aneuploidy screening . maternal blood sampling for -hcg and papp - a measurement was performed on the first appointment at 11 weeks . there was no relevant personal or family medical history or exposure to any known teratogen . abdominal ultrasound performed at 13 weeks of amenorrhoea revealed an intrauterine gestational sac containing a live fetus with a crown - rump length of 53 mm . a detailed sonographic examination detected caudal dysplasia with hypoplastic lower limbs ( figure 1 ) as well as an intra - abdominal cystic formation ( figure 2a ) , which was thought to correspond to the gastric bubble . the risk for aneuploidies , based on ultrasound and biochemical markers , was low ( trisomy 21  1:21163 , trisomy 13/18  1:37147 ) . regardless the uncertainty of the definitive diagnosis , the poor prognosis was discussed and the couple opted for medical termination of pregnancy , which was performed using a combined regimen of oral mifepristone and vaginal misoprostol . the fetal patho - histological study confirmed the sonographic findings and revealed additional multiple malformations : low - set ears , hypoplastic unilobated lungs , absent spleen , hypertrophic pyloric stenosis with marked stomach distension ( figure 2b ) , horseshoe dysplastic and cystic kidney with a single ureter , rudimentary bladder , bilateral intraabdominal testes , urethral and anal atresia , distended bowel , recto - perineal fistula and ambiguous genitalia . asymmetric lower limbs were also noticed , with absent foot and rudimentary leg on the left and syndactyly ( lobster claw malformation ) of the right foot ( figures 3 and 4 ) . placental study revealed nonspecific changes with increased fibrin deposits and lateral insertion of the umbilical cord , which had three vessels . placental weight and maturity were considered appropriate for the gestational age ( figure 3 ) . fetal x - ray revealed absent sacral and lower lumbar vertebrae , absent lower limb bones on the left and hypoplastic right femur and tibia as well as absent right fibula . absent pelvic bones on the left and hypoplastic on the right were also reported ( figure 5 ) . due to simultaneous occurrence of vertebral anomalies ( absent sacral and lower lumbar vertebrae ) , anal atresia , limb defect ( right tibial hypoplasia , absent lower left limb bones ) and renal defects ( horseshoe dysplastic cystic kidney ) , this complex polymalformative association represents a case of vacterl association . although limb malformations were classically defined as radial defects , the definition of vacterl currently includes a wider range of limb malformations . in this specific case , despite radial ray defects were not present , a preaxial lower limb anomaly ( tibial hypoplasia ) was observed . it has been described that tibial hypoplasia / aplasia represents the most common of lower limb malformations , occurring in over two thirds of patients . minor defects commonly observed in vacterl were also found in this case ( low - set ears , lung lobation defect , genital and gonadal anomalies and lobster claw malformation of lower extremity ) . although hypertrophic pyloric stenosis and asplenia are not typical features of vacterl , such anomalies have already been described in cases of vacterl association . cryptorchidism was also observed in this case . although it is not a feature frequently observed in vacterl association , these non - vacterl anomalies observed in the present case probably represent another spectrum of the disease . several studies have suggested that genitourinary malformations could be considered a secondary feature of vacterl association , as malformations affecting renal and genital systems often occur together due to the closely related embryological origin of both systems . the vast majority of cases are sporadic and only rare cases of familial links have been described . the risk of having an affected relative is low , therefore screening of first - degree relatives of an affected individual is not advocated . because vacterl association consists of anomalies of multiple systems , chromosomal disorders such as trisomy 18 and trisomy 13 vacterl association also shows some phenotypic overlap with other conditions , as digeorge , feingold , fryns , pallister - hall and townes - brocks syndromes . although prenatal diagnosis is challenging , its suspicion is extremely important due to the generally poor prognosis of this association . when diagnosis before viability is possible , management options can be discussed with the couple , including medical termination of pregnancy . even when the decision to continue the pregnancy is taken , prenatal diagnosis is very important to improve outcome . in this cases , planning for delivery in a tertiary centre and neonatal differentiated care have impact on prognosis .
vacterl association ( omim 192350 ) is a non - random combination of multiple congenital malformations including vertebral , anal , cardiac , tracheoesophageal , renal and limb anomalies . 
 the wide spectrum of defects suggests the occurrence of defective development during early embryogenesis . 
 the authors report a case of a complex polymalformative association detected by ultrasound in the first trimester of pregnancy . 
 the ensuing fetal study revealed the presence of vertebral , anorectal , renal and limb anomalies and therefore was considered a case of vacterl association . 
 this complex association generally entails a poor prognosis . 
 its early detection allows discussion of management options , including medical termination of pregnancy .