Rare Medical News

Disease Profile

VACTERL association

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q87.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

notapplicable.svg

Other names (AKA)

VATER association

Categories

Congenital and Genetic Diseases; Digestive Diseases; Kidney and Urinary Diseases

Summary

VACTERL association is a non-random association of birth defects that affects multiple parts of the body. The term VACTERL is an acronym with each letter representing the first letter of one of the more common findings seen in affected individuals: (V) = vertebral abnormalities; (A) = anal atresia; (C) = cardiac (heart) defects; (T) = tracheal anomalies including tracheoesophageal (TE) fistula; (E) = esophageal atresia; (R) = renal (kidney) and radial (thumb side of hand) abnormalities; and (L) = other limb abnormalities. Other features may include (less frequently) growth deficiencies and failure to thrive; facial asymmetry (hemifacial microsomia); external ear malformations; intestinal malrotation; and genital anomalies. Intelligence is usually normal. The exact cause of VACTERL association is unknown; most cases occur randomly, for no apparent reason. In rare cases, VACTERL association has occurred in more than one family member.[1] Treatment depends on the symptoms, and may include surgery to repair the birth defects, followed by long-term managment.[2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Anal atresia
Absent anus
0002023
Aplasia/Hypoplasia of the lungs
Absent/small lungs
Absent/underdeveloped lungs

[ more ]

0006703
Polyhydramnios
High levels of amniotic fluid
0001561
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Tracheal stenosis
Narrowing of windpipe
0002777
30%-79% of people have these symptoms
Abnormal cardiac septum morphology
0001671
Aplasia/Hypoplasia of the radius
0006501
Congenital diaphragmatic hernia
0000776
Ectopic kidney
Abnormal kidney location
Displaced kidney

[ more ]

0000086
Laryngomalacia
Softening of voice box tissue
0001601
Renal agenesis
Absent kidney
Missing kidney

[ more ]

0000104
Tracheoesophageal fistula
0002575
Vertebral segmentation defect
0003422
5%-29% of people have these symptoms
Abnormal morphology of female internal genitalia
0000008
Abnormal sacrum morphology
0005107
Abnormality of the gallbladder
0005264
Abnormality of the intervertebral disk
0005108
Abnormality of the pancreas
0001732
Abnormality of the ribs
Rib abnormalities
0000772
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Anencephaly
0002323
Bifid scrotum
Cleft of scrotum
0000048
Cavernous hemangioma
Collection of dilated blood vessels that forms mass
0001048
Cleft palate
Cleft roof of mouth
0000175
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Finger syndactyly
0006101
Hydronephrosis
0000126
Hypoplasia of penis
Underdeveloped penis
0008736
Hypospadias
0000047
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Large fontanelles
Wide fontanelles
0000239
Low-set, posteriorly rotated ears
0000368
Multicystic kidney dysplasia
0000003
Non-midline cleft lip
0100335
Occipital encephalocele
Brain tissue sticks out through back of skull
0002085
Omphalocele
0001539
Preaxial hand polydactyly
Extra thumb
0001177
Single umbilical artery
Only one artery in umbilical cord instead of two
0001195
Percent of people who have these symptoms is not available through HPO
Abnormal nasopharynx morphology
0001739
Abnormal sternum morphology
Abnormality of the sternum
Sternal anomalies

[ more ]

0000766
Abnormal vertebral morphology
0003468
Absent radius
Missing outer large bone of forearm
0003974
Choanal atresia
Blockage of the rear opening of the nasal cavity
Obstruction of the rear opening of the nasal cavity

[ more ]

0000453
Esophageal atresia
Birth defect in which part of esophagus did not develop
0002032
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Hypoplasia of the radius
Underdeveloped outer large forearm bone
0002984
Laryngeal stenosis
0001602
Patent ductus arteriosus
0001643
Patent urachus
0010479
Postnatal growth retardation
Growth delay as children
0008897
Preaxial polydactyly
0100258
Radioulnar synostosis
Fused forearm bones
0002974
Renal dysplasia
0000110
Scoliosis
0002650
Short thumb
Short thumbs
Small thumbs

[ more ]

0009778
Spina bifida
0002414
Sporadic
No previous family history
0003745
Syndactyly
Webbed fingers or toes
0001159
Tethered cord
0002144
Tetralogy of Fallot
0001636
Transposition of the great arteries
0001669
Triphalangeal thumb
Finger-like thumb
0001199
Ureteropelvic junction obstruction
0000074
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Vesicoureteral reflux
0000076

Cause

A specific, consistent, genetic abnormality has not been identified in individuals with VACTERL association.[1] A very few sporadic cases of VACTERL association have been associated with mutations in FGF8, HOXD13, ZIC3, PTEN, FANCB, FOXF1, and TRAP1 genes and mitochondrial DNA.[3]

When a condition is defined as being an "association", it means that it is made up of a series of specific features which have been found to occur together more often than it would happen due to chance alone, but for which no specific cause has been determined (idiopathic). For indiviuals with VACTERL association, the risk for it to recur in either a sibling or a child is usually quoted as being around 1% (1 in 100). There are very few reports of recurrence of the VACTERL association in families in the literature.[1]

Researchers have stated that when dysmorphic features, growth abnormalities, and/or learning disability are present in addition to the features of VACTERL association, it may actually be due to a syndrome or chromosome abnormality; if this is the case, the recurrence risk for a family member would be the risk that is associated with that specific diagnosis. Genetic disorders which have features in common with VACTERL association include Feingold syndrome, CHARGE syndrome, Fanconi anemia, Townes-Brocks syndrome, and Pallister-Hall syndrome. It has also been recognized that there is a two‐ to threefold increase in the incidence of multiple congenital malformations (with features that have overlapped with those of VACTERL association) in children of diabetic mothers.[4]

Diagnosis

There is no available objective laboratory test for VACTERL association. The diagnosis is based on having at least three of the following features (which make up the acronym VACTERL):[2][5] 

(V) Vertebral defects, commonly accompanied by rib anomalies;

(A) imperforate Anus or Anal atresia;

(C) Cardiac (heart) defects;

(T) Tracheo-Esophageal fistula

(E) Esophageal atresia;

(R) Renal (kidney) anomalies including renal agenesis, horseshoe kidney, and cystic and/or dysplastic kidneys; 

(L) Limb abnormalities.

Because these malformations were observed to occur together more often than would be expected by chance alone (but for which no specific cause has been determined), the condition was termed an association. The diagnosis is a diagnosis of exclusion, which means that other conditions need to be ruled out before making a diagnosis of VACTERL.[2] 

To make a diagnosis, a genetic doctor will typically conduct a very detailed physical exam, collect a family history, and investigate the presence of internal malformations. Supporting evaluations, such as genetic testing to rule out other similar syndromes, may also be needed. Depending on the features present, some conditions that may be considered when diagnosing a person who has features of VACTERL association (differential diagnosis) may include:[2][5]

Treatment

Treatment for VACTERL association is based on the signs and symptoms present and may vary from person to person. It is best to work with your doctor to determine the signs and symptoms present and the available treatment options available for them. Care of people with VACTERL association may involve a team approach and include several different specialists, including a gastroenterologist, cardiologist, surgeon, urologist, and more.

Management Guidelines

  • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Social Networking Websites

        Organizations Providing General Support

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • Genetics Home Reference (GHR) contains information on VACTERL association. This website is maintained by the National Library of Medicine.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

            In-Depth Information

            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss VACTERL association. Click on the link to view a sample search on this topic.

              References

              1. Castori M. VACTERL Association. National Organization for Rare Disorders. 2015; https://rarediseases.org/rare-diseases/vacterl-association/.
              2. Solomon B. VACTERL/VATER association. Orphanet. December 2011; https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=603.
              3. Nakamura Y & cols. PCSK5 mutation in a patient with the VACTERL association. BMC Res Notes. June 9, 2015; 8:228. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4467638/.
              4. Shaw-Smith C. Oesophageal atresia, tracheo-oesophageal fistula, and the VACTERL association: review of genetics and epidemiology. Journal of Medical Genetics. July 2006; 43(7):545-554. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2564549/?tool=pubmed.
              5. Chen Y & cols.. The genetic landscape and clinical implications of vertebral anomalies in VACTERL association. Journal of Medical Genetics. 2016; 53(7):431-437. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941148/.

              Rare Medical News