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VACTERL with Hydrocephalus

Synonyms of VACTERL with Hydrocephalus

  • VACTERL Association with Hydrocephalus
  • VACTERL-H Association
  • VATER Association with Hydrocephalus

Disorder Subdivisions

  • No subdivisions found.

General Discussion

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.

Symptoms

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
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.

Anal Atresia
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.

Cardiac Defects
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.

Renal Abnormalities
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).

Limb Anomalies
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.

Causes

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.

Affected Populations

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.

Related Disorders

Symptoms of the following disorders can be similar to those of VACTERL with hydrocpehlaus. Comparisons may be useful for a differential diagnosis:

Fanconi's anemia, also known as Fanconi pancytopenia syndrome, is a rare genetic disorder characterized by deficiency of all blood cell types (pancytopenia), including red blood cells, white blood cells, and platelets. Such abnormalities may lead to abnormal bleeding and easy bruising, paleness of the skin (pallor), recurrent infection, and other findings that typically become apparent from approximately three to 10 years of age. However, in some cases, pancytopenia and associated abnormalities (hematologic findings) may occur as early as infancy or as late as the third decade of life. Individuals with Fanconi's anemia may also have abnormal, patchy, brownish discolorations of the skin; short stature; and certain congenital defects. These may include underdevelopment or absence of the thumbs and/or the bones on the thumb side of the forearms (radii); congenital hip dislocation; kidney (renal) malformations; cardiac defects; and/or other abnormalities. There are several different subtypes (complementation groups) of Fanconi's anemia, each of which is thought to result from changes (mutations) of different disease genes. The disorder is known to be associated with a high frequency of chromosomal breakage, a finding that may be helpful in distinguishing Fanconi's anemia from other disorders with similar symptoms and findings. Fanconi's anemia is inherited as an autosomal recessive trait. (For further information on this disorder, choose "Fanconi" as your search term in the Rare Disease Database.)

CHARGE association is a rare pattern of malformations that may affect several organ systems of the body. CHARGE is an acronym that stands for (C)oloboma of the eye; (H)eart defects; (A)tresia of the Choanae, meaning bony or membranous blockage of the passageway between the nose and throat; (R)etardation of growth and development and/or mental deficiency; (G)enital anomalies; and (E)ar anomalies and/or deafness. Four or more of these characteristic features must be present for a diagnosis of CHARGE association. Some affected individuals may also have other, variable symptoms and findings, such as a small head, incomplete closure of the roof of the mouth (cleft palate), an abnormal groove in the upper lip (cleft lip), swallowing difficulties, paralysis of facial nerves (facial palsy), an abnormal connection between the windpipe and the tube that carries food from the throat to the stomach (tracheoesophageal fistula), renal malformations, and/or other features. In most cases, CHARGE association appears to occur randomly for unknown reasons (sporadically); however, some familial cases have been reported. (For more information, choose "CHARGE" as your search term in the Rare Disease Database.)

Baller-Gerold syndrome is a rare genetic disorder characterized by distinctive malformations of the skull and facial (craniofacial) area and bones of the forearms and hands. In affected infants, there is premature fusion of the fibrous joints (cranial sutures) between certain bones in the skull (craniosynostosis). As a result, the head may appear unusually short and wide and/or pointed at the top (turribrachycephaly) or relatively triangular in shape (trigonocephaly). Additional craniofacial malformations may include a prominent forehead; downslanting eyelid folds (palpebral fissures); and/or small, malformed (dysplastic), low-set ears. Baller-Gerold syndrome is also characterized by underdevelopment (hypoplasia) or absence (aplasia) of the bone on the outer side of the forearms (radii). In addition, the bone on the pinky side of the forearms (ulnae) is unusually short and curved and the thumbs may be underdeveloped or absent. Some affected individuals also have congenital heart defects, such as an abnormal opening in the fibrous partition that separates the lower or upper chambers of the heart (ventricular or atrial septal defects) and/or patent ductus arteriosus (PDA). The latter is characterized by an abnormal opening between the artery that transports oxygen-rich blood to most of the body (aorta) and the pulmonary artery, which carries oxygen-deficient blood to the lungs. Some individuals with the disorder may also have kidney (renal) malformations, additional physical abnormalities, and/or mental retardation. Baller-Gerold syndrome is usually thought to be inherited as an autosomal recessive trait. (For further information, choose "Baller Gerold" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
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.

Treatment
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

For more information, please contact:

Synthes, Inc.
1302 Wrights Lane East
West Chester, PA 19380
800-523-0322

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to VACTERL with Hydrocephalus

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).

References

TEXTBOOKS
Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:664.

JOURNAL ARTICLES
Grech V, et al. VACTERL with hydrocephalus and isolated tracheo-oesophageal fistula in a first cousin. Clin Dysmorphol. 2000;9:145-6.

Onyeije CI, et al. Prenatal diagnosis of sirenomelia with bilateral hydrocephalus: report of a previously undocumented form of VACTERL-H association. Am J Perinatol. 1998;15:193-7.

Lomas FE, et al. VACTERL with hydrocephalus: family with X-linked VACTERL-H. Am J Med Genet. 1998;76:74-8.

Rossbach HC, et al. Fanconi anemia in brothers initially diagnosed with VACTERL association with hydrocephalus, and subsequently with Baller-Gerold syndrome. Am J Med Genet. 1996;61:65-7.

Froster UG, et al. VACTERL with hydrocephalus and branchial arch defects: prenatal, clinical, and autopsy findings in two brothers. Am J Med Genet. 1996;62:169-72.

Wang H, et al. VACTERL with hydrocephalus: spontaneous chromosome breakage and rearrangement in a family showing apparent sex-linked recessive inheritance. Am J Med Genet. 1993;47:114-7.

Vandenborre K, et al. VACTERL with hydrocephalus. A distinct entity with a variable spectrum of multiple congenital anomalies. Genet Cous. 1993;4:199-201. Erratum in: Genet Cous. 1994;5:123. Comment in: Genet Cous. 1995;6:69.

Iafolla AK, et al. VATER and hydrocephalus: distinct syndrome? Am J Med Genet. 1991;38:46-51.

Evans JA, et al. VACTERL with hydrocephalus: further delineation of the syndrome(s). Am J Med Genet. 1989;34:177-82.

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.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/04/18 00:00:00 GMT+0

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