Ivan Hayward, MD, Dolores H. Pretorius, MD*

*Perinatal Associates of California, 8010 Frost Street, San Diego, CA 92123. Ph: 619-543-6657, Fax 619-534-0721

Synonym: None.

Definition: Congenital varicella syndrome, a recognized entity of congenital abnormalities, caused by maternal chickenpox infection.

Prevalence: 1% of mothers affected with varicella during their pregnancy will have a fetus affected by varicella embryopathy.

Etiology: Maternal varicella infection.

Pathogenesis: Infection of fetus by maternal chickenpox crossing placenta.

Associated anomalies: Varicella embryopathy is manifested by growth retardation, limb hypoplasia, ocular abnormalities and central nervous system abnormalities.

Differential diagnosis: None.

Prognosis: Poor.

Recurrence risk: None.

Management: Supportive. Congenital varicella syndrome due to maternal chickenpox is a well described entity which may manifest growth retardation, limb hypoplasia with skin cicatrisation, ocular abnormalities (microophthalmia, chorioretinitis, cataracts), and central nervous system abnormalities (microcephaly, ventriculomegaly and atrophy)¹. A description of abnormalities seen sonographically in five affected fetuses has been reported².

MESH Varicella-zoster virus BDE 2499 ICD9 9771.8 CDC 771.280

Introduction

We report a case in which additional abnormalities (clavicle hypoplasia and diaphragmatic paralysis) were present prenatally; these abnormalities could potentially be identified with sonography.

Case report

A 32-year-old G2P1 presented to her obstetrician at twenty weeks gestation with a history of chickenpox six weeks earlier. A sonogram performed in the physicians office demonstrated small hyperechoic foci in the fetal abdomen which were felt to be within small bowel loops and of unclear significance (fig. 1).

Figure 1: Transverse image of fetal abdomen at 20 weeks showing multiple hyperechoic foci in the liver.

At thirty-four weeks of gestation, premature labor and preeclampsia led to a repeat cesarean section. Physical exam of the infant demonstrated that the right wrist and right knee were held in flexion. Skin cicatrization was noted over the right shoulder and neck to the level of the ear. Skin atrophy was also noted over the right antecubital space and over the right knee. Upon chest auscultation, decreased breath sounds were heard over the right lower hemithorax. Neurologic exam suggested nonfunction of the left seventh and eighth nerves, and Horner"s syndrome.

A chest film demonstrated elevation of the right hemidiaphragm and hypoplasia of the right clavicle (fig. 2). An abdominal sonogram demonstrated multiple hyperechogenic foci within the liver (fig. 3).  A sonogram of the head revealed no abnormalities.

Figure 2: Chest x-ray of newborn showing elevation of right   hemidiaphragm

Figure 3:  Transverse image of abdomen immediately after birth showing scattered bright echoes throughout liver.

Clinical follow-up at eight months of age reveals long term feeding difficulties with dysphagia necessitating gastric tube placement. Residual cranial nerve dysfunction, paralysis of the right hemidiaphragm and right hand flexion deformity persist.

Discussion

Thirty-four cases of varicella embryopathy have been described in the literature to date². These cases are a result of first or second trimester maternal varicella infection³. The risk of embryopathy following maternal infection is not known but is thought to be lower than the 4.9% figure previously reported^4,9.

Prenatal diagnosis

Only nine of the reported cases have been examined by intrauterine sonography². The sonographic abnormalities include hydrops, polyhydramnios, and hyperechogenic hepatic foci. Theoretically, abnormalities such as thoracic dysplasia, dextrocardia, clubbed feet, limb hypoplasia, cerebellar dysplasia, and ocular abnormalities which have been reported pathologically might also be seen sonographically. In the present case, clavicular hypoplasia and diaphragmatic paralysis might have been noted sonographically if diligently sought.

Findings

There is a range of severity of involvement from a lethal disseminated disease to relatively benign ocular or dermatologic abnormalities⁵. Hanshaw reported a 39% lethality in the syndrome; but with the addition of the more recently reported cases, this figure may be as high as 61% (17/28)².

The hyperechogenic foci within the liver in the present case were noted in three of the five affected fetuses we reported previously². Pathologically, these foci correspond to sites of dystrophic calcification. Similar calcifications have been reported in congenital herpes simplex and toxoplasmosis infections⁶.

Clavicular hypoplasia and diaphragmatic paralysis have not been reported previously, although limb hypoplasia and nerve paralysis have been described. Cranial nerve involvement and dysphagia have been previously described⁷. The unilaterality of this infants involvement has been seen in most cases and is in keeping with the theory of an intrauterine zoster-type infection⁸.

Although the syndrome of varicella embryopathy has been well described, the ability to detect abnormalities sonographically is not widely known, as was demonstrated in the present case. A thorough sonographic evaluation of the amniotic fluid status, limb length, orbit appearance, cerebral anatomy and liver echogenicity is useful in detecting affected fetuses and may eventually prove useful in predicting outcomes.

References

1. Gilstrap LC III, Sebastian F. Infections in Pregnancy.  Wiley-Liss: New York, 1990, pp. 177-184.

2. Pretorius D, Hayward I, Jones KL, Stamm E. Sonographic  evaluation of pregnancies with maternal varicella infection, JUM (In Press).

3. Burrow GN, Ferris TF. Medical Complications During  Pregnancy, 3rd ed., WB Saunders: Philadelphia, 1988, pp. 378- 380. 

4. Fox GN, Strangarity JW. Varicella-zoster virus infections in pregnancy. Am Fam Physician 39:89-98, 1989.

5. Hanshaw JB. Varicella-zoster infections. In: Viral Diseases of the Fetus and Newborn, 2nd Ed. WB Saunders: Philadelphia, 1985, pp. 161-174.

6. Shackelford GD, Kirks DR. Neonatal hepatic calcifications secondary to transplacental infection. Radiology 122:753-757, 1977.

7. Williamson AP. The varicella-zoster virus in the etiology of severe congenital defects. Clin Pediatr (Philadelphia) 14:553-559, 1975.

8. Higa K, Kenjiro D, Haruhiko M. Varicella-zoster infections during pregnancy: Hypothesis concerning the mechanisms of  congenital malformations. Obstet Gynecol 69:214-222, 1987.

9. Jones KL, unpublished data