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1999-09-03-05 Answer of case of the week #8 © Izquierdo

Case #8

September 3-17, 1999

Submitted by Luis A. Izquierdo, MD, Pensacola, Florida, USA

This is a 30-week fetus for which several images are provided. The fetus is measuring smaller than the size expected for the date. An karyotype was obtained that was normal.


The first two images represent axial views at the level of the bodies of the lateral ventricles. The striking finding is the marked periventricular echogenicity. Note also the dilatation of the ventricles at this level.

The third prenatal ultrasound image represents a sagittal view of the fetal brain with a significant dilatation of the lateral ventricles and the same periventricular echogenicity.

These are the postnatal MRI images revealing hydrocephaly, periventricular calcifications, cortical atrophy and no sulci.


Therefore this is a 30-week-old fetus is growth restricted has hydrocephaly as well as microcephaly and echogenic borders of the lateral ventricles. Although we had not given the biparietal measurement it can be "guestimated" form the second image to be around 60 mm and therefore around 24 weeks. Quite a severe microcephaly for a 30-week fetus !

There are few differential diagnoses for the periventricular echogenicity aside from calcification. Tubers (such as in tuberous sclerosis) are not that echogenic and not as numerous. Thus calcification is the more likely diagnosis.

Differential diagnoses

Since intracranial calcifications has such a small differential diagnosis we will use it as the main finding to search for the diagnosis.

Calcifications may occur in the following conditions:

  1. Viral infections such as:
    • Rubella: in the USA, only 10% of females are susceptible
    • Varicella-zoster: only 15% of females are susceptible
    • Herpes Simplex infection
    • Venezuelan Equine Encephalitis
    • Toxoplasmosis
    • Congenital Cytomegalovirus infection: most common congenitally acquired infection
  1. Infarctions
  2. Teratoma
  3. Familial mitochondrial encephalopathy
  4. 3-hydroxyisobutyric aciduria
  5. Moebius syndrome
  6. Fahr"s syndrome

Most of these diagnoses can readily be eliminated since they do not present with periventricular calcifications but instead basal ganglia or parenchymal calcifications. The only serious differential diagnosis is the Familial mitochondrial encephalopathy. The ultrasound findings of intracranial calcifications are mostly important to distinguish between CMV and Toxoplasmosis. CMV most commonly is represented in the periventricular area as compared to Toxoplasmosis where the lesions are seen more commonly in the brain parenchyma.

Diagnosis: Congenital CMV 


One of the most important developments in the management and treatment of perinatal viral infections has been the application of modern molecular biologic techniques such as PCR.

Cytomegalovirus is a DNA virus from the herpes virus group. It causes the most common congenitally acquired infection. There is a seroprevalence of this virus of 60% in USA. The congenital form happens in 0.5 to 2.5% of all newborns. Severe damage to the fetus as well as neonate occurs with an incidence between 1/5000 to 1/20,000 births. Full-blown cytomegalic inclusion disease is associated almost always to primary maternal infection.

The most common findings of congenitally acquired CMV infection include:

  1. petechial rash 79%
  2. hepatosplenomegaly 74%
  3. jaundice 63%
  4. microcephaly 50%

 As we can see, not all of these can be detected by ultrasound. Of the findings in fetuses with CMV disease, the following can be appreciated by ultrasound:

  1. hepatosplenomegaly
  2. microcephaly
  3. cerebral calcifications
  4. cerebellar and/or cortical atrophy
  5. hydrocephaly
  6. IUGR
  7. cardiomegaly
  8. ascites
  9. non immune hydrops fetalis

It is important to note that CMV like other herpes viruses, becomes latent. Because of latent disease, previous infection does not confer immunity against infection in the infant.

What labs can we do for the prenatal diagnosis of CMV infection

    1. Amniotic Fluid: CMV IgM, viral cultures, nucleic acids for PCR
    2. Fetal Blood: CMV IgM, viral cultures, nuclei acids for PCR, viral antigens

It is well known that culture for the CMV virus in the amniotic fluid is the most accurate method for the diagnosis of this infection.

A recent study by Bodeus et al. ( Prenat Diagn 1999; 19: 314-17) presents  98 pregnancies with CMV infection. Of these, 71 had either a culture and/or PCR.

The conclusions were that the best sensitivity of these tests is obtained after 23 weeks of gestation and this results in 95%. When compared in a 2x2 table these were the results:

Amniotic Fluid


















Teaching point:

The finding of a fetus that is growth restricted, has hydrocephaly, microcephaly and periventricular calcification should suggest cytomegalovirus infection.


Cytomegalovirus infections

Nigro G, La Torre R, Anceschi MM, Mazzocco M, Cosmi EV Hyperimmunoglobulin therapy for a twin fetus with cytomegalovirus infection and growth restriction. Am J Obstet Gynecol 1999 May;180(5):1222-6

II Institute of Gynecology and Obstetrics and the Pediatric Institute, La Sapienza University, Rome, Italy.

OBJECTIVE: Cytomegalovirus immunoglobulin was administered to a pregnant woman with primary cytomegalovirus infection and placental involvement of 1 twin fetus, in whom growth restriction had developed. STUDY DESIGN: Inhibition of viral activity was attempted by administration of high-titer cytomegalovirus neutralizing antibodies for therapy of the involved fetoplacental unit and prevention of cytomegalovirus infection in the uninfected twin fetus. RESULTS: After cytomegalovirus immunoglobulin infusions the placental edema decreased and the infected fetus started to grow once again, showing at birth only hepatosplenomegaly associated with viruria and cytomegalovirus deoxyribonucleic acidemia. Moreover, cytomegalovirus immunoglobulin G avidity increased and cell-mediated immunity improved. The other twin, who had negative results of cytomegalovirus culture and deoxyribonucleic acid detection at birth, was found to have cytomegalovirus deoxyribonucleic acid in the urine after 1 week. From the age of 9 months, however, both twins had persistent negative results of cytomegalovirus deoxyribonucleic acid detection. CONCLUSION: Although large-scale studies are needed to establish the real efficacy and the best therapeutic regimen, cytomegalovirus immunoglobulin may be considered for treatment or prevention of fetal cytomegalovirus infection.

Grangeot-Keros L, Simon B, Audibert F, Vial M Should we routinely screen for cytomegalovirus antibody during pregnancy? Intervirology 1998;41(4-5):158-62

Department of Microbiology and Immunology, Hopital Antoine Beclere, Clamart, France. 

In order to evaluate the usefulness of cytomegalovirus (CMV) antibody screening during pregnancy, women attending for antenatal care at the Antoine Beclere Hospital (Clamart, France) were prospectively studied during 22 months (1995-1996). Forty-five percent of these women were CMV-seropositive. Twenty suspected or confirmed CMV primary infections were detected. Nine infected infants were born to these women. All infected infants are now between 10 months and 2.5 years old. They all are asymptomatic even those who initially presented abnormal biological parameters or slightly abnormal ultrasound scans during fetal life. Presently, screening for CMV antibody cannot be recommended because it induces economic, psychological and ethical problems. Furthermore, there is no efficient and safe treatment available so far. However, we do think that large studies must be performed to increase our knowledge about the natural history of intrauterine CMV infection. This is also important for an improved assessment of the value of ultrasound examination results as well as the biological parameters measured in fetal blood samples.

Crino JP Ultrasound and fetal diagnosis of perinatal infection. Clin Obstet Gynecol 1999 Mar;42(1):71-80; quiz 174-5

University of Texas-Houston Medical School, USA.

Prenatal ultrasound can aid the clinician in evaluation of the patient with a suspected in utero TORCH infection, particularly toxoplasmosis, syphilis, and CMV. Demonstration of characteristic ultrasound findings in the high risk patient has a high predictive value for fetal infection and also may have prognostic significance. The sonologist should understand the limitations of ultrasound, discuss them with the patient, and document the discussion in the medical record. Patients should be counseled that ultrasound is not a sensitive test for fetal infection and that a normal fetal anatomy survey cannot predict a favorable outcome. In the low-risk patient, fetal infection should be considered when multiple organ system anomalies, fetal growth restriction, placental enlargement, or abnormalities of amniotic fluid volume are demonstrated.

Aubard Y, Rogez S, Darde ML, Fermeaux V, Servaud M, Lienhardt A Double maternal seroconversion to cytomegalovirus and Toxoplasma gondii. Eur J Obstet Gynecol Reprod Biol 1998 Oct;80(2):275-8

Gynecology Department, CHU Limoges, France. 

BACKGROUND: We report the first case of a double maternal seroconversion for Toxoplasma gondii (TG) and cytomegalovirus (CMV) diagnosed during pregnancy. CASE: One case is reported of a female patient referred for seroconversion in response to TG in the 27th week of gestation. A search for foetal involvement revealed signs of non-specific foetal infection without any TG-related lesions. Tests were carried out for another foeto-maternal infectious disease and maternal seroconversion in response to CMV was discovered with virus in the amniotic fluid. The foetus developed hydrocephalus and intracranial calcifications and the pregnancy was terminated at the parents" request. CMV-induced multiple organ involvement without any signs of Toxoplasma gondii-related involvement were noted in the foetus. CONCLUSIONS: This case indicates that a search should be made for another infectious disease likely to involve the foetus when non-specific signs of infection in the foetus are present, even though maternal seroconversion has been recognized.

Lazzarotto T, Guerra B, Spezzacatena P, Varani S, Gabrielli L, Pradelli P, Rumpianesi F, Banzi C, Bovicelli L, Landini MP Prenatal diagnosis of congenital cytomegalovirus infection. J Clin Microbiol 1998 Dec;36(12):3540-4

  Department of Clinical and Experimental Medicine, Section of Microbiology, Medical School, University of Bologna, Bologna, Italy.

We report here the results of a study on the prenatal diagnosis of congenital cytomegalovirus (CMV) infection. The study was carried out by both PCR and virus isolation from amniotic fluid (AF) for 82 pregnant women at risk of transmitting CMV for the detection of (i) seroconversion to CMV immunoglobulin G (IgG) positivity during the first trimester of pregnancy, (ii) symptomatic CMV infection in the mother during the first trimester of pregnancy or intrauterine growth retardation detected by ultrasound or abnormal ultrasonographic findings suggestive of fetal infections, and (iii) seropositivity for CMV-specific IgM. For 50 women, fetal blood (FB) was also obtained and tests for antigenemia and PCR were performed. The results indicate that AF is better than FB for the prenatal diagnosis of CMV infection. PCR with AF has a sensitivity (SNS) of 100%, a specificity (SPE) of 83.3%, a positive predictive value (PPV) of 40%, and a negative predictive value (NPV) of 100%; rapid virus isolation with the same material has an SNS of 50%, an SPE of 100%, a PPV of 100%, and an NPV of 94.7%. Fewer than 10% of the women positive for IgM by enzyme immunoassay (EIA) had a congenitally infected fetus or newborn infant. When EIA IgM positivity was confirmed by Western blotting (WB) and the WB profile was considered, the percent transmission detected among women with an "at-risk" profile was higher than that observed among IgM-positive women and was the same as that among women who seroconverted during the first trimester of pregnancy (transmission rates of 29 and 25%, respectively).

Carillo C, Cerenzia G, Serrao L, Niccoli VS [Current orientation about congenital Cytomegalovirus infection]. Clin Ter 1997 Oct;148(10):437-42

  I Clinica Ostetrica e Ginecologica, Policlinico Umberto I, Roma.

The CMV infection in pregnancy make serious problems about the diagnosis and the fetal prognosis. Infact primary infection by CMV is loaded by an high risk of congenital infection and the presence of antibodies IgG do not prevent a possible reinfection. Furthermore, the latent presence in the host of CMV induces his reactivation when the immunosorveillance decreases during pregnancy. The consequences of primary infection are well shown during pregnancy and they are very grave, but also the reactivations induce especially neurological consequences, that however are shown only after some months from delivery. Therefore in consideration of the prognosis and the poor therapeutics, the management in these cases is essentially to give minute details to the mother about all the consequences for the fetus without to exclude, because of serious sequels, so that just she can to decide the future of her pregnancy.

Lipitz S, Yagel S, Shalev E, Achiron R, Mashiach S, Schiff E Prenatal diagnosis of fetal primary cytomegalovirus infection. Obstet Gynecol 1997 May;89(5 Pt 1):763-7

  Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Israel.

OBJECTIVE: To evaluate the validity of prenatal diagnosis work-up for congenital cytomegalovirus (CMV) in women with primary infection. METHODS: Sixty-three pregnant women with primary cytomegalovirus disease (including two with twin pregnancies), referred to three tertiary perinatal centers over 4 years, underwent evaluation for congenital cytomegalovirus. Fetal diagnosis was made after 21 weeks" gestation by amniocentesis and fetal blood sampling (40 subjects), or amniocentesis only (23 subjects). RESULTS: Twenty-two (35%) pregnancies showed evidence of vertical transmission: 13 of them underwent funipuncture, but only ten (77%) of the 13 showed positive immunoglobulin (Ig)-M results in fetal blood. No cases of positive fetal serum Ig-M with negative amniotic fluid culture or polymerase chain reaction were observed. In nine (41%) of the 22 pregnancies with evidence of vertical transmission, abnormal ultrasonographic findings were recorded. Six (27%) women with evidence of vertical transmission continued their pregnancies and in only one (with prenatal ultrasonographic abnormalities) was an infant born with neurologic sequelae. In 41 (65%) pregnancies, no evidence of vertical transmission was found, and 37 continued to term. Only one newborn from this subgroup subsequently showed mild motor disability during a median of 23 months of follow-up. CONCLUSION: Among pregnant patients with primary CMV infection, analysis of amniotic fluid detected all of the infected fetuses. Thus, this is a reliable tool for counseling pregnant women with primary infection. This may guide the patient as to whether or not pregnancy can be continued with a high level of confidence.

 Watt-Morse ML, Laifer SA, Hill LM The natural history of fetal cytomegalovirus infection as assessed by serial ultrasound and fetal blood sampling: a case report. Prenat Diagn 1995 Jun;15(6):567-70

Department of Obstetrics and Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Magee-Womens Hospital, PA 15213, USA.

A patient in whom intrauterine fetal cytomegalovirus (CMV) infection was diagnosed at approximately 25 weeks" gestation is presented. The fetus was evaluated by serial fetal blood samplings and ultrasound examinations. The fetus manifested evidence of severe thrombocytopenia and hepatic inflammation, with recovery over a period of approximately 8 weeks. The initial sonographic findings of marked fetal ascites and cardiomegaly gradually resolved; ventriculomegaly developed during the third trimester. At delivery, the baby was morphologically normal with the exception of mild ventriculomegaly. Cord blood was negative for CMV IgM but urine was culture-positive for CMV. At age 3, the child has a severe but stable unilateral hearing deficit and is otherwise developmentally normal. This case demonstrates the utility of serial ultrasound and fetal blood sampling in the prenatal diagnosis and management of fetal CMV infection.

Achiron R, Pinhas-Hamiel O, Lipitz S, Heiman Z, Reichman B, Mashiach S Prenatal ultrasonographic diagnosis of fetal cerebral ventriculitis associated with asymptomatic maternal cytomegalovirus infection. Prenat Diagn 1994 Jul;14(7):523-6

Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Israel.

Cytomegalovirus is the most common cause of congenital viral infection. In utero infection is usually suspected in patients with growth-retarded fetuses or when maternal illness precipitates serological investigations. A case is presented where routine ultrasound examination at 30 weeks" gestation in an asymptomatic patient demonstrated mild fetal ventriculomegaly. Transvaginal ultrasound enabled the visualization of intraventricular adhesions and small periventricular cysts. The suspected diagnosis of in utero cytomegalovirus infection was confirmed by the presence of IgM antibodies in fetal blood and subsequently by isolation of the virus from the infant"s urine. The presence of mild fetal ventriculomegaly should prompt transvaginal brain imaging.

Donner C, Liesnard C, Content J, Busine A, Aderca J, Rodesch F Prenatal diagnosis of 52 pregnancies at risk for congenital cytomegalovirus infection. Obstet Gynecol 1993 Oct;82(4 Pt 1):481-6

Department of Obstetrics and Gynecology, Hopital Universitaire Erasme, Free University of Brussels, Belgium.

OBJECTIVE: To determine the feasibility of prenatal diagnosis of fetal cytomegalovirus (CMV) infection. METHODS: Fifty-two pregnant women were investigated in our unit between October 1985 and July 1992. The diagnostic procedures included ultrasound examination, amniocentesis, and fetal blood sampling. Specific tests for CMV infection included specific immunoglobulin (Ig) M antibodies, viral culture, and amplification of CMV DNA by polymerase chain reaction. Nonspecific tests included white blood cell count, hemoglobin, hematocrit, platelets, and gamma-glutamyl transferase determination. RESULTS: The combination of tests allowed an antenatal diagnosis of CMV in 13 of the 16 infected fetuses (sensitivity 81%). Amniocentesis allowed the diagnosis in 12 of the 13 antenatally diagnosed cases. The sensitivity of CMV IgM antibody detection in fetal blood was 69%. The culture of fetal blood was never positive. Thrombocytopenia was present in six cases, and ultrasound was abnormal in five. CONCLUSIONS: Amniotic fluid is the best sample to diagnose CMV infection, and fetal blood sampling and sonography are important to assess the fetal condition. Our experience underscores the importance of repetitive sampling.

Twickler DM, Perlman J, Maberry MC Congenital cytomegalovirus infection presenting as cerebral ventriculomegaly on antenatal sonography. Am J Perinatol 1993 Sep;10(5):404-6

Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9032.

Antenatal sonography in two cases demonstrated cerebral ventriculomegaly and decreased head circumference, subsequently found to be secondary to cytomegalovirus (CMV) infection. In both cases, the lateral ventricles were enlarged and lissencephaly was diagnosed in the neonatal period. The findings of ventriculomegaly and decreased head circumference on antenatal sonography warrant further investigation for CMV via amniotic fluid cultures or fetal blood, given the poor prognosis in infants with symptomatic infection.

Hogge WA, Buffone GJ, Hogge JS Prenatal diagnosis of cytomegalovirus (CMV) infection: a preliminary report. Prenat Diagn 1993 Feb;13(2):131-6

Department of Obstetrics and Gynecology, University of Maryland, Baltimore.

Eight patients were referred for prenatal diagnosis for suspected fetal cytomegalovirus infection (CMV): six for documented first-trimester infection and two for abnormal ultrasound evaluation suggestive of fetal infection. Three methods of diagnosis were employed: (1) amniotic fluid viral cultures and CMV-specific IgM in fetal serum; (2) amniotic fluid cultures and detection by polymerase chain reaction amplification of CMV-specific DNA in chorionic villi; and (3) detection of CMV-specific DNA in villus samples only. Amniotic fluid cultures detected all cases of infection, but CMV-specific IgM was not a reliable indicator of infection in any case. DNA analysis correlated well with both culture results and clinical outcome.

Parisot S, Droulle P, Feldmann M, Pinaud P, Marchal C Unusual encephaloclastic lesions with paraventricular calcification in congenital rubella. Pediatr Radiol 1991;21(3):229-30

Service de Neonatalogie et de Pediatrie, CHR de Metz-Thionville, Hopital Bel-Air, Thionville, France.

We report an unusual case of congenital rubella. The infant was suffering from a serious encephalopathy, and both prenatal echography and neonatal CT scan showed passive ventriculomegaly with a calcified periventricular border. Usually, such lesions are strongly suggestive of cytomegalovirus (CMV) infection and have never previously been reported in congenital rubella. Classic cerebral lesions in rubella are related to a prominent obstructive vasculopathy. Conversely, encephaloclastic lesions in CMV infection are likely related to a necrosis of brain parenchyma following upon an initial ventriculitis, and perhaps also to a disturbance of neuronal proliferation. Recently, Carey described a neonate with proven congenital rubella and cranial ultrasound findings typical of ventriculitis. However, in spite of the close similarity between our patient"s lesions and the typical CMV lesions, we think it"s impossible to assert similar pathogenic mechanisms. Actually, it"s quite conceivable that only a severe or extensive vasculopathy can lead to brain atrophy with periventricular calcification in congenital rubella.

Weiner CP, Grose C Prenatal diagnosis of congenital cytomegalovirus infection by virus isolation from amniotic fluid. Am J Obstet Gynecol 1990 Oct;163(4 Pt 1):1253-5

Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City.

Cytomegalovirus was isolated antenatally from the amniotic fluid of two pregnant women. In both cases prenatal diagnosis of the fetal virus infection aided the subsequent management of the mother and newborn infant.

Grose C, Weiner CP Prenatal diagnosis of congenital cytomegalovirus infection: two decades later. Am J Obstet Gynecol 1990 Aug;163(2):447-50

Department of Pediatrics, University of Iowa College of Medicine, Iowa City.

Cytomegalovirus is the most common cause of congenital infection in the United States, yet there has been little progress in the prenatal diagnosis of this intrauterine infection. We present evidence that viral culture of amniotic fluid may be a useful adjunct procedure, when performed as part of the antenatal evaluation of suspected fetal cytomegalovirus infection.

Comment in: Am J Obstet Gynecol 1991 Jun;164(6 Pt 1):1687

Szeifert G, Csecsei K, Toth Z, Papp Z Prenatal diagnosis of ascites caused by cytomegalovirus hepatitis. Acta Paediatr Hung 1985;26(4):311-6

The case of a 23-weeks-old fetus is described in whom prenatal ultrasonography revealed ascites accompanied by an increased alpha-fetoprotein concentration in the amnial fluid. Detailed embryopathological work-up carried out after induced abortion demonstrated generalized cytomegalovirus disease and furnished histological proof of transplacental propagation.

Hayward JC, Titelbaum DS, Clancy RR, Zimmerman RA Lissencephaly-pachygyria associated with congenital cytomegalovirus infection. J Child Neurol 1991 Apr;6(2):109-14

Division of Neurology, Children"s Hospital of Philadelphia, PA 19104.

We report the presence of major cerebral migrational defects in five severely, multiply handicapped children with congenital cytomegalovirus (CMV) infection. These patients had both computed tomographic (CT) scan and magnetic resonance imaging (MRI) evidence of marked migrational central nervous system defects consistent anatomically with the spectrum of lissencephaly-pachygyria, a disorder commonly idiopathic or associated with chromosomal abnormalities or with unknown early gestational insults. Neuroradiologic features included broad, flat gyri, shallow sulci, incomplete opercularization, ventriculomegaly, periventricular calcifications, and white-matter hypodensity on CT scans or increased signal intensity on long-TR MRI scans. Evidence for congenital CMV infection included prenatal onset of microcephaly, periventricular calcifications, neonatal jaundice, hepatomegaly, elevated CMV-specific immunoglobulin M, or viral isolation from urine. Previous reports of the neurologic sequelae of CMV have emphasized varying degrees of psychomotor retardation, cerebral palsy and epilepsy due to polymicrogyria, periventricular calcification, microcephaly, or rarely, hydrocephalus. Our patients appear to represent extremely severe examples of the effects of CMV on neurologic growth, maturation, and development. Recognition of these severe migrational abnormalities was improved by use of MRI, a technique that affords superior definition of the nature and extent of gyral and white-matter abnormalities. We suggest that these abnormalities may be more common than has previously been recognized.

Tassin GB, Maklad NF, Stewart RR, Bell ME Cytomegalic inclusion disease: intrauterine sonographic diagnosis using findings involving the brain. AJNR Am J Neuroradiol 1991 Jan-Feb;12(1):117-22

Department of Diagnostic Radiology, University of Texas Health Science Center, Houston 77030.

Two second-trimester cases and one third-trimester case of intrauterine cytomegalic inclusion disease (CID) are presented, each having a different intracranial sonographic presentation. The findings are correlated with radiographic studies and the known pathophysiology. Sonographic evidence of intrauterine cerebral necrosis or calcification should alert one to the possibility of CID, particularly if other signs of in utero infection are present. A pattern of bilateral periventricular calcifications, which may be preceded by hypoechoic periventricular ringlike zones, seems to be specific for intrauterine CID. However, CID also may result in widespread cerebral destruction. If the sonographic study produces an uncertain diagnosis, sonography can still aid in the prenatal diagnosis of CID by guiding percutaneous umbilical cord blood sampling for serology or by directing amniocentesis for cytomegalovirus culture. The ability of sonography to demonstrate specific characteristics of CID in utero enables prenatal diagnosis of this disease

Graham D, Guidi SM, Sanders RC Sonographic features of in utero periventricular calcification due to cytomegalovirus infection. J Ultrasound Med 1982 May;1(4):171-2


Differential diagnoses

Samson JF, Barth PG, de Vries JI, Menko FH, Ruitenbeek W, van Oost BA, Jakobs C  Familial mitochondrial encephalopathy with fetal ultrasonographic ventriculomegaly and intracerebral calcifications.  Eur J Pediatr 1994 Jul;153(7):510-6

Department of Paediatrics, Free University Hospital, Amsterdam, The Netherlands.

In two sibs antenatal ultrasonography revealed identical intracranial calcification, ventricular widening and microcephaly. The first pregnancy was artificially terminated at 19 weeks. Post-mortem examination of the brain revealed destructive calcification and extracerebral neuronal heterotopia. The second sib went to term but died 48 h after birth from irreversible lactic acidosis. Autopsy showed extensive encephalopathy with cavitation and calcification in the cerebral hemispheres, polymicrogyria, multiple neuronal heterotopia, partial callosal dysgenesis, and severe Leigh syndrome, together forming a continuum of early and late brain disruption. Mitochondrial respiratory chain abnormalities, mainly affecting complexes I and IV, and deficiency of pyruvate dehydrogenase complex were detected in skeletal muscle and in liver. A normal functioning of the respiratory chain was found in the fibroblasts. Analysis of mtDNA from muscle, liver and blood revealed normal amounts of intact mtDNA without any of the known point mutations associated with MELAS, MERRF or Leigh syndromes. The early fetal disruption and necrotic changes in the brains of sibs indicate a specific genetically determined disorder which affects neuronal migration, a finding not previously associated with respiratory chain disorders. The present disorder may mimic antenatal congenital infectious encephalopathy because of the combined finding of microcephaly and destructive intracerebral calcification.

Mansour AM, Nichols MM Congenital diffuse necrotizing herpetic retinitis. Graefes Arch Clin Exp Ophthalmol 1993 Feb;231(2):95-8

Department of Ophthalmology, University of Texas Medical Branch, Galveston 77550.

Neonatal Herpes simplex infections are usually contracted from the birth canal, and the systemic lesions develop several days to weeks after delivery. We present the clinicopathologic findings in a newborn with a prenatal diagnosis of hydrocephalus who died at 1 day of age. Severe liquefaction necrosis and foci of calcification were present in the brain, adrenal glands, and retina. Cowdry type A intranuclear inclusions were present in the adrenal glands and retina. There was no clinical evidence of genital herpes in either parent. This is the first documented case of in utero transmission of Herpes simplex infection, confirmed by the polymerase chain reaction, and causing fulminant necrotizing retinitis and encephalitis

Chitayat D, Meagher-Villemure K, Mamer OA, O"Gorman A, Hoar DI, Silver K, Scriver CR Brain dysgenesis and congenital intracerebral calcification associated with 3-hydroxyisobutyric aciduria. J Pediatr 1992 Jul;121(1):86-9

Division of Medical Genetics, Montreal Children"s Hospital, Quebec, Canada.

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