The VACTERL association (also VATER association, and less accurately VACTERL syndrome) refers to a recognized group of
birth defect
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities ca ...
s which tend to co-occur (see below). This pattern is a recognized association, as opposed to a
syndrome
A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek language, Greek σύνδρομον, meaning "concurrence". When a sy ...
, because there is no known pathogenetic cause to explain the grouped incidence.
Each child with this condition can be unique. At present this condition is treated after birth with issues being approached one at a time. Some infants are born with symptoms that cannot be treated and they do not survive. Also, VACTERL association can be linked to other similar conditions such as Klippel Feil and
Goldenhar syndrome
Goldenhar syndrome is a rare congenital defect characterized by incomplete development of the ear, nose, soft palate, lip and mandible on usually one side of the body. Common clinical manifestations include limbal dermoids, preauricular skin ta ...
including crossovers of conditions.
No specific genetic or chromosome problem has been identified with VACTERL association. VACTERL can be seen with some chromosomal defects such as
Trisomy 18
A trisomy is a type of polysomy in which there are three instances of a particular chromosome, instead of the normal two. A trisomy is a type of aneuploidy (an abnormal number of chromosomes).
Description and causes
Most organisms that reprodu ...
and is more frequently seen in babies of diabetic mothers. VACTERL association, however, is most likely caused by multiple factors.
VACTERL association specifically refers to the abnormalities in structures derived from the embryonic mesoderm.
Signs and symptoms
The following features are observed with VACTERL association:
* V -
Vertebral anomalies
Congenital vertebral anomalies are a collection of malformations of the spine. Most, around 85%, are not clinically significant, but they can cause compression of the spinal cord by deforming the vertebral canal or causing instability. This condit ...
* A -
Anorectal malformations
An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unknow ...
Tracheoesophageal fistula
A tracheoesophageal fistula (TEF, or TOF; see spelling differences) is an abnormal connection (fistula) between the esophagus and the trachea. TEF is a common congenital abnormality, but when occurring late in life is usually the sequela of surgic ...
* E -
Esophageal atresia Esophageal can refer to:
* The esophagus
* Esophageal arteries
* Esophageal glands
* Esophageal cancer
Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include ...
radial
Radial is a geometric term of location which may refer to:
Mathematics and Direction
* Vector (geometric), a line
* Radius, adjective form of
* Radial distance, a directional coordinate in a polar coordinate system
* Radial set
* A bearing f ...
anomalies
* L - Limb defects
Although it was not conclusive whether VACTERL should be defined by at least two or three component defects, it is typically defined by the presence of at least three of the above congenital malformations.
Spine
Vertebral anomalies, or defects of the spinal column, usually consist of small (
hypoplastic
Hypoplasia (from Ancient Greek :wikt:ὑπό, ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.scoliosis, or curvature of the spine.
Anal defects
Anal atresia
An imperforate anus or anorectal malformations (ARMs) are birth defects in which the rectum is malformed. ARMs are a spectrum of different congenital anomalies which vary from fairly minor lesions to complex anomalies. The cause of ARMs is unknow ...
or imperforate anus is seen in about 55 to 90 percent of patients with VACTERL association. These anomalies are usually noted at birth. It often require surgery in the first days of life. Sometimes babies will require several surgeries to fully reconstruct the intestine and anal canal.
Cardiac defects
Up to 75 percent of patients with VACTERL association have been reported to have
congenital heart disease
A congenital heart defect (CHD), also known as a congenital heart anomaly and congenital heart disease, is a defect in the structure of the heart or great vessels that is present at birth. A congenital heart defect is classed as a cardiovascular ...
. The most common heart defects seen with VACTERL association are
ventricular septal defect
A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart. The extent of the opening may vary from pin size to complete absence of the ventricular septum, creating one ...
(VSD),
atrial septal defect
Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the foramen ovale; however, when this d ...
s and
tetralogy of Fallot
Tetralogy of Fallot (TOF), formerly known as Steno-Fallot tetralogy, is a congenital heart defect characterized by four specific cardiac defects. Classically, the four defects are:
*pulmonary stenosis, which is narrowing of the exit from the r ...
.
Less common defects are
truncus arteriosus
The truncus arteriosus is a structure that is present during embryonic development. It is an arterial trunk that originates from both ventricles of the heart that later divides into the aorta and the pulmonary trunk.
Structure
The truncus arterio ...
and
transposition of the great arteries
Transposition of the great vessels (TGV) is a group of congenital heart defects involving an abnormal spatial arrangement of any of the great vessels: superior and/or inferior venae cavae, pulmonary artery, pulmonary veins, and aorta. Congenital ...
. It is subsequently thought that cardiac defects should be considered an ''extension'' of VACTERL.
Trachea and oesophagus
Oesophageal atresia
The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to th ...
with
tracheoesophageal fistula
A tracheoesophageal fistula (TEF, or TOF; see spelling differences) is an abnormal connection (fistula) between the esophagus and the trachea. TEF is a common congenital abnormality, but when occurring late in life is usually the sequela of surgic ...
(TO fistula or TOF) is seen in about 70 percent of patients with VACTERL association, although it can frequently occur as an isolated defect. 15 to 33 percent of patients with TO fistulas will also have congenital heart disease. However these babies usually have uncomplicated heart defects, like a
ventricular septal defect
A ventricular septal defect (VSD) is a defect in the ventricular septum, the wall dividing the left and right ventricles of the heart. The extent of the opening may vary from pin size to complete absence of the ventricular septum, creating one ...
, which may not require any surgery.
Kidneys
Kidney defects are seen in approximately 50 percent of patients with VACTERL association. In addition, up to 35 percent of patients with VACTERL association have a
single umbilical artery
Occasionally, there is only the one single umbilical artery (SUA) present in the umbilical cord. This is sometimes also called a two-vessel umbilical cord, or two-vessel cord. Approximately, this affects between 1 in 100 and 1 in 500 pregnancies, m ...
(there are usually two arteries and one vein) which is often associated with additional kidney or urologic problems. Renal abnormalities in VACTERL association can be severe, with incomplete formation of one or both kidneys or urologic abnormalities such as obstruction of outflow of urine from the kidneys or severe reflux (backflow) of urine into the kidneys from the bladder. These problems can cause
kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
early in life and may require
kidney transplant
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor (formerly known as cadaveric) or living-donor transplantati ...
. Many of these problems can be corrected surgically before any damage can occur.
Limbs
Limb defects occur in up to 70 percent of babies with VACTERL association and include a displaced or hypoplastic thumb, extra digits (
polydactyly
Polydactyly or polydactylism (), also known as hyperdactyly, is an anomaly in humans and animals resulting in supernumerary fingers and/or toes. Polydactyly is the opposite of oligodactyly (fewer fingers or toes).
Signs and symptoms
In human ...
), fusion of digits (
syndactyly
Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and diprotodontia, but is an unusual condition in humans. The term is from Greek σύν, ''syn'' 'together' and δά ...
) and forearm defects such as
radial aplasia
Radial aplasia is a congenital defect which affects the formation of the radius bone in the arm. The radius is the lateral bone (thumb side) which connects the humerus of the upper arm to the wrist via articulation with the carpal bones. A child ...
. Babies with limb defects on both sides tend to have kidney or urologic defects on both sides, while babies with limb defects on only one side of the body tend to have kidney problems on that same side.
Extension
Features secondary to VACTERL components are frequent enough to be considered an extension of VACTERL. These include:
single umbilical artery
Occasionally, there is only the one single umbilical artery (SUA) present in the umbilical cord. This is sometimes also called a two-vessel umbilical cord, or two-vessel cord. Approximately, this affects between 1 in 100 and 1 in 500 pregnancies, m ...
,
ambiguous genitalia
Intersex people are individuals born with any of several sex characteristics including chromosome patterns, gonads, or genitals that, according to the Office of the United Nations High Commissioner for Human Rights, "do not fit typical bin ...
,
abdominal wall defect
Abdominal wall defects are a type of congenital defect that allows the stomach, the intestines, or other organs to protrude through an unusual opening that forms on the abdomen.
During the development of the fetus, many unexpected changes occur i ...
s,
diaphragmatic hernia
Diaphragmatic hernia is a defect or hole in the diaphragm that allows the abdominal contents to move into the chest cavity. Treatment is usually surgical.
Types
* Congenital diaphragmatic hernia
** Morgagni's hernia
** Bochdalek hernia
* Hiatal ...
, intestinal and respiratory anomalies, and oligohydramnios sequence defects. Cardiac defects are thought to fit in this category.
Growth
Many babies with VACTERL are born small and have difficulty with gaining weight. Babies with VACTERL association, however, do tend to have normal development and normal intelligence.
Pathology
Patients with abnormal cardiac and kidney function may be more at risk for
hemolytic uremic syndrome
Hemolysis or haemolysis (), also known by several other names, is the rupturing ( lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may occur in vivo ...
.
Diagnosis
Differential diagnosis
*
Baller–Gerold syndrome
Baller–Gerold syndrome (BGS) is a rare genetic syndrome that involves premature fusion of the skull bones and malformations of facial, forearm and hand bones. The symptoms of Baller–Gerold syndrome overlap with features of a few other genetics ...
Currarino syndrome
Currarino syndrome is an inherited congenital disorder where either the sacrum (the fused vertebrae forming the back of the pelvis) is not formed properly, or there is a mass in the presacral space in front of the sacrum, and there are malformatio ...
*
DiGeorge syndrome
DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facial features, frequent i ...
*
Fanconi anemia
Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of no ...
Holt–Oram syndrome
Holt–Oram syndrome (also called atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome, heart-hand syndrome type 1, HOS, ventriculo-radial syndrome) is an autosomal dominant disorder that affects bones in the arms and hands (the u ...
*
Pallister–Hall syndrome
Pallister–Hall syndrome (abbreviated PHS) is a disorder that affects the development of many parts of the body.
It is named for Judith Goslin Hall, Judith Hall and Philip Pallister.
Presentation
Most people with this condition have extra fing ...
*
Townes–Brocks syndrome
Townes–Brocks syndrome (TBS) is a rare genetic disease that has been described in approximately 200 cases in the published literature. It affects both males and females equally.
* VACTERL with hydrocephalus
Management
Epidemiology
The incidence of VACTERL association is estimated to be approximately 1 in 10,000 to 1 in 40,000 live-born infants. It is seen more frequently in infants born to
diabetic
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
mothers. While most cases are sporadic, there are clearly families who present with multiple involved members.
History
The acronym ''VATER'' association was first described by Linda Quan, an emergency room physician, and David Smith, a man who was considered the father of
dysmorphology
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The relate ...
in 1972, to define a non-random co-occurrence of the listed defects. Years later, research revealed that cardiac and renal abnormalities were common in the association, and the acronym was changed to ''VACTERL''. However, no single cause was identified that links all these conditions together. Therefore, this VACTERL is termed as "association" instead of a "syndrome".
The differentiation of the acronyms VACTERL and VATER is due to the variation in defects determined at or prior to birth. VACTERL contains vertebral, anal, cardiac, trachea-esophageal, renal/kidney, and limb defects where as VATER only has vertebral, anal, trachea-esophageal, and renal defects. The "R" in VATER represented radial dysplasia. Though the differences are clear, the physical defects vary from case to case.
See also
*
22q11 deletion syndrome
DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a syndrome caused by a microdeletion on the long arm of chromosome 22 (human), chromosome 22. While the symptoms can vary, they often include congenital heart problems, specific facia ...
Holt–Oram syndrome
Holt–Oram syndrome (also called atrio-digital syndrome, atriodigital dysplasia, cardiac-limb syndrome, heart-hand syndrome type 1, HOS, ventriculo-radial syndrome) is an autosomal dominant disorder that affects bones in the arms and hands (the u ...
Pallister–Hall syndrome
Pallister–Hall syndrome (abbreviated PHS) is a disorder that affects the development of many parts of the body.
It is named for Judith Goslin Hall, Judith Hall and Philip Pallister.
Presentation
Most people with this condition have extra fing ...
*
Townes–Brocks syndrome
Townes–Brocks syndrome (TBS) is a rare genetic disease that has been described in approximately 200 cases in the published literature. It affects both males and females equally.