Congenital Varicella Syndrome

Congenital Varicella Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Congenital Varicella Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Fetal Effects of Chickenpox
  • Fetal Varicella Infection
  • Fetal Varicella Zoster Syndrome
  • Fetal Effects of Varicella Zoster Virus
  • Varicella Embryopathy

Disorder Subdivisions

  • None

General Discussion

Congenital Varicella Syndrome is an extremely rare disorder in which affected infants have distinctive abnormalities at birth (congenital) due to the mother's infection with chickenpox (maternal varicella zoster) early during pregnancy (i.e., up to 20 weeks gestation). Affected newborns may have a low birth weight and characteristic abnormalities of the skin; the arms, legs, hands, and/or feet (extremities); the brain; the eyes; and/or, in rare cases, other areas of the body. The range and severity of associated symptoms and physical findings may vary greatly from case to case depending upon when maternal varicella zoster infection occurred during fetal development.



In many cases, newborns with Congenital Varicella Syndrome may be abnormally small and have a low birth weight due to abnormal growth delays during fetal development (intrauterine growth retardation). In addition, distinctive skin abnormalities are often present. Certain areas of the skin may consist of thickened, overgrown (hypertrophic) scar tissue (cicatrix), and surrounding skin may appear abnormally hardened (indurate), red, and inflamed (erythema). Such cicatrix scarring typically occurs on one or more of the arms and/or legs, which may also be malformed, underdeveloped (hypoplastic), and abnormally shortened (reduction deformities). Affected infants may also exhibit incomplete development (hypoplasia) of certain fingers and/or toes (rudimentary digits).



In some cases, newborns with Congenital Varicella Syndrome may have abnormalities of the brain such as degeneration of the outer portion of the brain (cortical atrophy) and/or abnormal enlargement of cavities of the brain (dilated ventricles [ventriculomegaly]). There may also be abnormalities of the part of the nervous system that controls involuntary functions (autonomic nervous system) such as damage to or abnormalities of certain nerve fibers (sympathetic nerve fibers) that pass from the spinal cord to the neck and/or pelvic area. Some affected infants and children may also exhibit abnormal smallness of the head (microcephaly), delays in the acquisition of skills requiring the coordination of mental and physical activities (psychomotor retardation), varying degrees of mental retardation, and/or learning disabilities. In some cases, characteristic eye (ocular) abnormalities may also be present including loss of transparency of the lenses of the eyes (cataracts); abnormal smallness of one or both eyes (unilateral or bilateral microphthalmia); involuntary, rapid, side-to-side movements of the eyes (pendular nystagmus); and/or inflammation and scarring of certain membranes of the eyes (chorioretinitis and chorioretinal scarring). Such ocular abnormalities may result in varying degrees of visual impairment. In rare cases, newborns with Congenital Varicella Syndrome may have additional abnormalities associated with the disorder.

Symptoms

Affected newborns may have low birth weight and characteristic abnormalities of the skin; the arms, legs, hands, and/or feet (extremities); the brain; the eyes; and/or, in rare cases, other areas of the body. The range and severity of symptoms and physical findings may vary greatly from case to case depending upon when maternal chickenpox occurred during fetal development. For example, while some affected infants may exhibit only characteristic skin and limb malformations, others may have only specific eye abnormalities (e.g., cataracts) and/or may experience symptoms associated with brain involvement.



In many cases of congenital varicella syndrome, abnormal growth delays occur during fetal development (intrauterine growth retardation). As a result, most affected newborns are abnormally small and have low birth weight.



Many newborns with CVS also have distinctive skin abnormalities. In many cases, certain areas of the skin may consist of scar tissue (cicatricial) that is thickened and overgrown (hypertrophic). Such scarring may appear in a characteristic "zigzag" pattern, and the surrounding skin may be abnormally hardened (indurate) and appear red and inflamed (erythematic). In most cases, cicatrix scarring occurs on one or more of the arms and/or legs. Affected arms and/or legs and/or fingers or toes may also be malformed, underdeveloped (hypoplastic).



Some newborns with CVS may have damage to the brain and/or other parts of the central nervous system. A small head (microcephaly) or uncontrolled electrical disturbances in the brain (seizures) are among the symptoms sometimes encountered. In some cases, cerebrospinal fluid may accumulate within the hollow spaces of the brain (ventricles) leading to an enlarged head (hydrocephalus). Developmental delays including varying degrees of mental retardation may be present.



In some cases, affected infants may have Horner's syndrome, a condition resulting from damage to or abnormalities of nerve fibers (sympathetic nerve fibers) passing from the spinal cord to certain areas of the face, eyes, and eyelids. Associated symptoms, which affect one side of the face, may include "sinking in" of the eyeball, drooping of the upper eyelid (ptosis), raised lower eyelid, abnormal narrowing (constriction) of the pupil, and flushing and absence of sweating (anhidrosis) on the affected side of the face. (For more information on this condition, use "Horner" as your search term in the Rare Disease Database.)



In addition, in some cases, due to damage to sympathic nerve fibers passing to the pelvic area, affected infants may experience impaired functioning of certain bands of muscle fibers (sphincters) that help ensure the proper passage of feces (anal sphincter dysfunction) and urine (urethral sphincter). As a result, affected children may experience an inability to voluntarily retain feces in the rectum (fecal incontinence) as well as involuntary, uncontrolled urination (urinary incontinence).



Distinctive abnormalities of the eyes may also be present. These may include abnormally small eye(s) (unilateral or bilateral microphthalmia); abnormal clouding of the lenses of the eyes (cataracts); and/or involuntary, rapid, side-to-side movements of the eyes (pendular nystagmus). In addition, the nerve-rich membrane lining the inside of the back of the eyes (retina) and the thin membranous layer of blood vessels behind the retina (choroid) may exhibit inflammation (chorioretinitis) that may lead to scarring (chorioretinal scarring). Such inflammatory changes and chorioretinal scarring may, in turn, result in blurred vision and abnormal sensitivity to light (photophobia).



Children with CVS may have an increased susceptibility to Herpes zoster infection within the first two years of life. Herpes zoster infection, usually a problem of older people, results from the reactivation of varicella zoster virus that has remained dormant in certain nerve tissues. (For more information on this condition, please see the "Related Disorders" section of this report below.)

Causes

Congenital varicella syndrome is an extremely rare disorder in which affected infants demonstrate distinctive abnormalities at birth due to the mother's infection with chickenpox (maternal varicella zoster) early during pregnancy.



The varicella zoster virus (VZV) is one of several belonging to a family of viruses known as herpesviruses. A susceptible individual's initial exposure to the virus (i.e., through respiration or direct contact with vesicular fluid) usually results in chickenpox, a highly contagious infectious disease. Although most individuals contract chickenpox during childhood, those who do not will remain suspectible to the disorder during adulthood.



If a woman who has not had the disorder contracts chickenpox during pregnancy, it is possible that the developing fetus may also become infected. In approximately two percent of such cases, fetal exposure to the virus during the first 20 weeks of pregnancy (particularly during the sixth to the 20th week of gestation) may result in congenital varicella syndrome. According to researchers, when VZV infection occurs later during pregnancy (i.e., in the middle of the second or in the third trimester), the developing fetus' defense mechanisms against infection (fetal immune system) may be able to mount a response to the invading organism, typically resulting in a benign course. However, when VZV infection occurs early during fetal development, the immature fetal immune system may be unable to fight the invading virus, potentially resulting in CVS.



Many researchers believe that the symptoms and signs of CVS result from damage to the nervous system during early fetal development. The varicella zoster virus invades the fetal nerves (e.g., optic stalk, cervical cord, lumbosacral cord) leading to reduced development of nerve supply and/or damaged conduction of nerve signals (denervation) to certain tissues (e.g., within the eyes, extremities, etc.). This damage results in many of the abnormalities associated with the disorder. Although it is not fully understood why certain areas of the body seem particularly affected by fetal VZV infection, researchers speculate that the virus may affect those tissues undergoing rapid development such as those areas of the developing fetus that differentiate into the extremities (limb buds).

Affected Populations

Congenital varicella syndrome is an extremely rare disorder that appears to affect male and female newborns in equal numbers. Symptoms and physical characteristics associated with the disorder are apparent at birth.



CVS occurs in about 1-7 of 10,000 pregnancies. If CVS develops within the final days before delivery, or within a day or two afterward, there is a risk of neonatal varicella that can be severe and even life-threatening.

Standard Therapies

Diagnosis

A diagnosis of congenital varicella syndrome is usually suggested by confirmation of maternal varicella zoster infection early during pregnancy and the presence of certain characteristic symptoms and physical findings in the developing fetus or newborn.



In some cases, prenatal ultrasound studies may reveal distinctive limb malformations, craniofacial abnormalities, and/or other characteristic findings suggestive of the disorder. In other cases, a sample of fluid that surrounds the developing fetus (amniocentesis) and/or a tissue sample from a portion of the placenta (chorionic villus sampling [CVS]) may be removed and studied to confirm infection with varicella zoster virus (VZV).



Several tests may be used to analyze the liquid portion of the blood (serum) for evidence of varicella zoster virus infection (serological tests) in affected infants. For example, serum tests may reveal the presence of antibodies (IgG, VZV-specific IgM) to varicella zoster virus (VZV) up to several months or more after birth.



Treatment

The treatment of congenital varicella syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, infectious disease specialists, neurologists, eye specialists (ophthalmologists), surgeons, physical therapists, and/or other health care professionals may need to prepare systematic and comprehensive plans for an affected infant's treatment.



If a non-immune pregnant woman is exposed to chickenpox, varicella zoster immunoglobulin (VZIG) should be administered as soon as possible after exposure. VZIG is apparently most effective if used within 72 hours of exposure. However, some studies show that there are benefits for mother and child to be gained from the administration of VZIG for up to 10 days following exposure.



Newborn children of infected mothers should be given VZIG as soon as possible after birth. Such treatment seems to reduce the severity of the neonatal disease or, in some few cases, to prevent neonatal disease.



In many cases, physicians may recommend that females of child-bearing age who have not contracted chickenpox (seronegative) be immunized with the chickenpox vaccine to help prevent the occurrence of VZV infection during pregnancy and thus to avoid potential congenital varicella syndrome. However, it is essential that such vaccination be received under the recommendations of women's personal physicians. Because the chickenpox vaccine contains live, weakened strains of the VZV virus (live attenuated varicella virus), vaccination may, in some rare cases, result in disease in certain females who may have weakened immune systems (e.g., due to primary immunodeficiency disease, treatment with immunosuppressant medications, etc.).

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 website.



For information about clinical trials being conducted at the National Institutes of Health (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



The use of antiviral agents, such as acyclovir and ganciclovir, in the management of CVS remains under investigation. No anti-viral agent is approved for use in pregnancy at this time. Acyclovir has been used most often in various studies.

References

TEXTBOOKS

Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2330-32.



Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:1162-63.



Fields BN, Knipe DM., eds. Fields Virology. 2nd ed. Raven Press. New York, NY; 1990:2011-53.



Mandell GL, Bennett JE, Dolan R., eds. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 4th ed. Churchill Livingstone Inc. New York, NY; 1995:1345-51.



Behrman RE, Kliegman RM, Arvin AM., eds. Nelson Textbook of Pediatrics. 15th ed. W.B. Saunder Company. Philadelphia, PA; 1996:525-26.



REVIEW ARTICLES

Mirlesse V, Lebon P. [Chickenpox during pregnancy]Arch Pediatr. 2003;10:1113-18. French.



McCarter-Spaulding DE. Varicella infection in pregnancy. J Obstet Gynecol Neonatal Nurs. 2001;30:667-73.



Sauerbrei A, Wutzler P. The congenital varicella syndrome. J Perinatal. 2000;17:253-56.



Alfonso I, Alfonso DT, Papazian O. Focal upper extremity neuropathy in neonates. Semin Pediatr Neurol. 2000;7:4-14.



JOURNAL ARTICLES

Johannson AB, Rassart A, Blum D, et al. Lower-limb hypoplasia due to intrauterine infection with herpes simplex virus type 2: possible confusion with intrauterine varicella-zoster syndrome. Clin Infect Dis. 2004;38:e57-62.



Fujita H, Yoshii A, Maeda J, et al. Genitourinary anomaly in congenital varicella syndrome: case report and review. Pediatr Nephrol. 2004;19:554-57.



Koren G. Risk of varicella infection during late pregnancy. Can Fam Physician. 2003;49:1445-46.



Harger JH, Ernest JM, Thurnau GR, et al. Frequency of congenital varicella syndrome in a prospective cohort of 347 pregnant women. Obstet Gynecol. 2002;100:260-65.



Dimova PS, Karparov AA. Congenital varicella syndrome: case with isolated brain damage. J Child Neurol. 2001;16:595-97.



Kent A, Paes B. Congenital varicella syndrome: a rare case of central nervous system involvement without dermatological features. Am J Perinatol. 2000;17:253-56.



Cooper C, Wojtulewicz J, Ratnamohan VM, et al. Congenital varicella syndrome diagnosed by polymerase chain reaction - scarring of the spinal cord, not the skin. J Paediatr Child Health. 2000;36:186-88.



Hartung J, Enders G, Chaoui R, et al. Prenatal diagnosis of congenital varicella syndrome and detaction of varicella-zoster virus in the fetus: a case report. Prenat Diagn. 1999;19:163-66.



FROM THE INTERNET

Varicella Vaccine - FAQs Related to Pregnancy. National Immunization Program. CDC. Last modified on February 15, 2001. 4pp.

www.cdc.gov/nip/vaccine/varicella/ faqs-clinic-vac-preg.htm



Laartz B, Gompf SG, Allaboun K, Viral Infections and Pregnancy. emedicine. Last Updated: February 5, 2004. 11pp.

www.emedicine.com/med/topic3270.htm



Robert-Gnasia E. Embryopathie de virus varicelle. Orphanet. October 2003. 3pp.

www.orpha.net/data/patho/FR/fr-varicella.pdf

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