VACTERL with hydrocephalus is an extremely rare genetic disorder in which the multisystem features of VACTERL association occur in addition to hydrocephalus. The term VACTERL is an acronym with each letter representing the first letter of the more common findings seen in affected children:
(V) = vertebral abnormalities
(A) = anal atresia
(C) = cardiac (heart) defects
(T) = tracheoesophageal fistula
(E) = esophageal atresia
(R) = renal (kidney) abnormalities
(L) = limb abnormalities
Hydrocephalus is a condition in which accumulation of excessive cerebrospinal fluid (CSF) in the skull causes pressure on the tissues of the brain, resulting in a variety of symptoms. VACTERL with hydrocephalus is inherited as an autosomal recessive or X-linked recessive trait. VACTERL with hydrocephalus is a distinct genetic disorder separate from VACTERL association, a nonrandom association of birth defects.
VACTERL with hydrocephalus is a rare genetic disorder that affects multiple organ systems. Affected children have multiple problems apparent at birth (congenital birth defects). Additional characteristics of VACTERL with hydrocephalus do not develop or are not apparent until later during life. The diagnosis of VACTERL with hydrocephalus is usually made based on the presence of at least two or three of the characteristic findings of VACTERL association occurring along with hydrocephalus. The specific symptoms will vary greatly from one child to another. Some cases may be mild; others may have life-threatening complications such as respiratory failure.
Hydrocephalus is a condition in which excessive accumulation of cerebrospinal fluid in the skull causes pressure on the tissues of the brain and may result in abnormally enlarged head size (macrocephaly). Additional common symptoms associated with hydrocephalus include vomiting, irritability, seizures, and downward gaze of the eyes (sunsetting). In some cases, affected infants may experience delays in reaching developmental milestones (developmental delays). The specific symptoms associated with hydrocephalus vary from one child to another.
In addition to hydrocephalus, affected infants will have at least two to three of the characteristic symptoms of VACTERL association. Affected children will not have all of the symptoms listed below.
Vertebral abnormalities are defects of the spinal column. Children with VACTERL with hydrocephalus may have underdeveloped bones of the spine (hemivertebrae), missing ribs, extra ribs, and/or incomplete closure of the bones of the spinal column (spina bifida). In some cases, abnormal side-to-side curvature of the spine (scoliosis) and absence of the tailbone, which is the lowest bone of the spinal column, (sacral agenesis) may also occur.
Some children with VACTERL with hydrocephalus may have a condition in which a thin covering blocks the anal opening or the passage that normally connects the anus and the lowest part of the large intestine (rectum) fails to develop, a condition is known as anal atresia or imperforate anus. This condition prevents the normal passage of bowel contents.
Children with VACTERL with hydrocephalus may have a variety of congenital heart defects including ventricular septal defects (VSDs). The normal heart has four chambers. The two upper chambers, known as atria, are separated from each other by a fibrous partition known as the atrial septum. The two lower chambers are known as ventricles and are separated from each other by the ventricular septum. Valves connect the atria (left and right) to their respective ventricles. The aorta, the main vessel of arterial circulation, carries blood away from the left ventricle to the rest of the body. A VSD may occur in any portion of the ventricular septum. The size and location of the defect determine the severity of the symptoms. A small ventricular septal defect may close on its own (spontaneously) or become less significant as the child matures and grows. A moderately-sized defect may affect the ability of the heart to pump blood efficiently to the lungs and the rest of the body (congestive heart failure). Symptoms associated with heart failure may include an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), failure to grow at the expected rate (failure to thrive), and/or other findings. A large ventricular septal defect may cause life-threatening complications during infancy.
Additional congenital heart defects associated with the disorder may include atrial septal defects (ASDs); hypoplastic left heart syndrome, a condition in which there is underdevelopment of the left ventricle, the aortic and/or mitral valve, and the ascending aorta; patent ductus arteriosus, a condition in which the passage (ductus) between the blood vessel that leads to the lungs (pulmonary artery) and the major artery of the body (aorta) fails to close after birth; transposition of the great arteries, a condition in which the aortic and pulmonary arteries are in one another’s normal positions; and a condition known as tetralogy of Fallot. (For more information on this disorder, choose “Tetralogy of Fallot” in the Rare Disease Database.)
Tracheoesophageal Fistula and/or Esophageal Atresia
Children with VACTERL with hydrocephalus often have an abnormal connection between the windpipe and the tube that carries food from the throat to the stomach (tracheoesophageal fistula) potentially causing food to be inhaled (aspirated) into the lungs, which, in turn, may result in respiratory infections (e.g., pneumonia). In addition, esophageal atresia may be present. Esophageal atresia is a condition in which the tube (esophagus) that normally carries food from the mouth to the stomach narrows to a thin cord or ends in a pouch rather than providing passage to the stomach. These two conditions may result in feeding and swallowing difficulties.
Children with VACTERL with hydrocephalus often have a variety of abnormalities affecting the kidneys and urinary tract including lack of development of one or both kidneys (renal aplasia), malformation of one or both kidneys (renal dysplasia), displaced or malpositioned kidneys (renal ectopia), abnormal backflow (reflux) of urine into the tube (ureter) that carries urine to the bladder (vesicoureteral reflux), resulting in abnormal accumulation of urine in the kidneys (hydronephrosis). In addition, affected children may experience frequent urinary tract infections and the urethral opening may not be at the end of the penis (hypospadias).
Another major finding associated with VACTERL with hydrocephalus are defects affecting the lower arm bone on the thumb side (radius). These defects may include failure of the radius to grow (radial aplasia), underdevelopment of the radius (radial hypoplasia), underdevelopment or absence of the thumb and/or the presence of an extra bone in the thumb (triphalangeal tumb). In addition, affected children may have extra fingers (polydactyly), webbing of the fingers (syndactyly), and/or abnormal fusion of the two forearm bones (radiaoulnar synostosis).
Some infants with VACTERL with hydrocephalus may experience growth deficiencies and failure to thrive. In some cases, a single umbilical artery instead of the normal two may be present.
VACTERL with hydrocephalus is inherited as an autosomal recessive or X-linked recessive trait.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is turned off. Males have one X chromosome and if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males can not pass an X-linked gene to their sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% to have a son affected with the disease, and a 25% chance to have an unaffected son.
VACTERL with hydrocephalus is an extremely rare disorder that affects males and females in equal numbers. The exact prevalence of the disorder in the general population is unknown.
A diagnosis may be made based upon a complete physical exam and a variety of specialized tests to look for the major and minor features of VACTERL association occurring along with hydrocephalus.
The treatment of VACTERL with hydrocephalus is directed toward the specific symptoms that are apparent in each individual, which often varies greatly. Many of the structural abnormalities (radial defects, heart defects, anal atresia, etc.) can be surgically corrected. Hydrocephalus may be treated by the insertion of a tube (shunt) to drain excess cerebrospinal fluid (CSF) away from the brain and into another part of the body where the CSF can be absorbed.
Infants diagnosed with VACTERL with hydrocephalus will need to be followed by a number of medical and developmental specialists depending on their individual needs. Some of the medical specialists who often follow children with VACTERL with hydrocephalus include cardiologists, urologists, orthopedists, and ear, nose and throat physicians.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. A team approach is essential for these complex children.
The Vertical Expandable Prosthetic Titanium Rib (VEPTR) was approved by the FDA in 2004 as a treatment for thoracic insufficiency syndrome (TIS) in pediatric patients. TIS is a congenital condition where severe deformities of the chest, spine, and ribs prevent normal breathing and lung development. The VEPTR is an implanted, expandable device that helps straighten the spine and separate ribs so that the lungs can grow and fill with enough air to breathe. The length of the device can be adjusted as the patient grows. The titanium rib was developed at the University of Texas Health Science Center in San Antonio. It is manufactured by Synthes Spine Co.. http://www.synthes.com/sites/NA/Products/Spine/Screw_Hook_Rod_and_Clamp_System/Pages/VEPTR_and_VEPTR_II.aspx
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Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder (e.g., heart defects, anal atresia, tracheoesophageal fistula).
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FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:314390; Last Update:3/23/98. Entry No:276950; Last Update:11/27/02.
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