AJR 2000; 175:1067-1069
© American Roentgen Ray Society
Tuberous Sclerosis in the Fetus
Second-Trimester Diagnosis of Subependymal Tubers with Ultrafast MR Imaging
D. Levine1,2,
P. Barnes1,
B. Korf3 and
R. Edelman1
1
Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline
Ave., Boston, MA 02215.
2
Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center,
Boston, MA 02215.
3
Center for Human Genetics, HIM, Ste. 640, 77 Ave. Louis Pasteur, Boston, MA
02115.
Received January 19, 2000;
accepted after revision February 28, 2000.
Supported by grant NS 37945 from the National Institutes of Health.
Address correspondence to D. Levine.
Introduction
Tuberous sclerosis is an autosomal dominant multisystem disorder with
effects on the skin, brain, heart, and other organs. The estimated prevalence
is approximately one case per 6000—10,000 individuals. The classic
findings are angiofibroma, epilepsy, and mental retardation. Mental
retardation of a moderate to severe degree occurs in approximately half of the
patients. Seizures are present in 60-80% of patients.
Two genes, designated TSC1 (9q34) and TSC2 on (16p13),
are associated with tuberous sclerosis complex
[1,
2]. Genetic testing is not yet
available for prenatal diagnosis because of the genetic heterogeneity of the
tuberous sclerosis complex and the wide variety of mutations, many of which
are not amenable to the commonly used mutation detection systems.
Antenatal diagnosis has previously been based on the sonographic detection
of cardiac rhabdomyomas [3].
These rhabdomyomas can be seen in the mid second trimester, as early as 20
weeks [4]. The diagnosis of
tuberous sclerosis complex increases with the number of tumors, with from 30%
or less of the cases occurring when a single rhabdomyoma is present to 80%
when two or more tumors are present
[5]. In a study by Sonigo et
al. [6], 87% of fetuses with
cardiac rhabdomyomas had tuberous sclerosis. However, only approximately half
of the patients with tuberous sclerosis have cardiac rhabdomyomas
[7], most of which are not
present at the typical time of prenatal screening at 20 weeks' gestation. This
finding emphasizes the issue that currently available screening for tuberous
sclerosis complex lacks sensitivity in the second trimester.
In this report, we describe the visualization of a subependymal tuber at 21
weeks' gestation on prenatal MR imaging. Use of prenatal MR imaging in
addition to prenatal sonography has the potential to improve genetic
counseling and prenatal diagnosis of patients with tuberous sclerosis.
Case Report
A 31-year-old woman presented for genetic counseling because her husband
and one child have tuberous sclerosis. As part of a research protocol,
approved by the committee on clinical investigations at Beth Israel Deaconess
Medical Center, she was enrolled to have fetal sonography and fetal MR
examinations at 21 and 32 weeks' gestational age. Written informed consent was
obtained. At the time of the first sonogram, the fetus was noted to have two
cardiac rhabdomyomas (Fig. 1A).
The remainder of the sonographic fetal survey, including images of the brain,
was normal. The patient was counseled that the fetus likely was affected with
tuberous sclerosis and that the results of the MR examination likely would not
change her treatment. She elected to continue in the research protocol.
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Fig. 1A. —31-year-old woman who presented for genetic counseling because her
husband and one child have tuberous sclerosis. Fetus was screened for tuberous
sclerosis. Oblique sonogram obtained at 21 weeks' gestational age shows
echogenic mass (arrow) in left ventricle of heart consistent with
rhabdomyoma.
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MR imaging was performed of the fetus on a 1.5-T superconductive system
(Vision; Siemens, Erlangen, Germany) with a four-element phased array surface
coil. The whole-body specific absorption rate was less than 3.0 W/kg.
Half-Fourier acquisition single-shot turbo spin-echo (HASTE) images were
acquired in the axial, coronal, and sagittal planes (echo spacing, 4.2 msec;
effective TE, 60 msec; echo train length, 72; number of acquisitions, one;
section thickness, 4 mm; field of view, 26 x 35 cm; acquisition matrix,
192 x 256). A 130° refocusing pulse was used to minimize the amount
of radiofrequency power deposition. The scan time was 420 msec per image with
a 1-sec delay between acquisitions applied to decrease the specific absorption
rate. An image from each scan served as the scout for the subsequent sequence.
The total scan time for a single data acquisition of 13 sections was 17 sec.
The MR examination revealed a focal 2-mm low-signal-intensity nodule in the
periventricular region on the right (Fig.
1B). This nodule was seen in two separate image acquisitions in
orthogonal planes. The lesion caused a contour deformity of the ventricular
wall. The patient was counseled that this lesion likely was a subependymal
tuber, but because prenatal diagnosis had not been made previously at this
early gestational age, it was not certain whether this finding could be an
artifact.
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Fig. 1B. —31-year-old woman who presented for genetic counseling because her
husband and one child have tuberous sclerosis. Fetus was screened for tuberous
sclerosis. Coronal half-Fourier acquisition single-shot turbo spin-echo
(HASTE) MR image obtained at 21 weeks' gestational age shows 2-mm
low-signal-intensity nodule (arrow) in subependymal region.
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The patient elected to continue the pregnancy and returned for imaging at
32 weeks' gestation. At that time, three cardiac rhabdomyomas were visualized
on sonography. The remainder of the sonographic fetal survey, including images
of the brain, was normal. Fetal MR imaging showed at least seven subependymal
low-signal-intensity nodules, one of which was in the region seen on the MR
images at 21 weeks' gestational age (Figs.
1C and
1D), and one subcortical
low-signal-intensity nodule.
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Fig. 1C. —31-year-old woman who presented for genetic counseling because her
husband and one child have tuberous sclerosis. Fetus was screened for tuberous
sclerosis. Coronal (C) and sagittal (D) HASTE MR images at 32
weeks' gestational age show low-signal-intensity nodule (arrow) in
location similar to that seen in B. Other low-signal-intensity nodules
were seen in subependymal and subcortical regions (not shown).
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Fig. 1D. —31-year-old woman who presented for genetic counseling because her
husband and one child have tuberous sclerosis. Fetus was screened for tuberous
sclerosis. Coronal (C) and sagittal (D) HASTE MR images at 32
weeks' gestational age show low-signal-intensity nodule (arrow) in
location similar to that seen in B. Other low-signal-intensity nodules
were seen in subependymal and subcortical regions (not shown).
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MR imaging after birth was performed using a standard neonatal brain
protocol. The image in this case report has the following scan parameters: a
TR/TE of 500/14, two acquisitions, 4-mm section thickness, a field of view of
17.5 x 20 cm, and an acquisition matrix of 112 x 256. This study
confirmed the presence of multiple subependymal and cortical tubers
(Fig. 1E).
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Fig. 1E. —31-year-old women who presented for genetic counseling because her
husband and one child have tuberous sclerosis. Fetus was screened for tuberous
sclerosis. Sagittal T1-weighted MR image obtained on day of birth shows
high-signal-intensity nodule (arrow) in location similar to that in
D. Other subependymal and cortical tubers also were present (not
shown).
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A second case of second-trimester diagnosis of (presumed) tuberous
sclerosis is shown in Figure 2.
Review of 180 fetal MR examinations revealed no similar subependymal lesions
in patients examined for other indications.
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Fig. 2. —37-year-old woman was referred at 24 weeks' gestation for tuberous
sclerosis screening because three cardiac rhabdomyomas were seen on routine
prenatal sonogram. No family history of tuberous sclerosis was present. Axial
half-Fourier acquisition single-shot turbo spin-echo MR image shows multiple
small low-signal-intensity nodules (arrows) in periventricular
regions that were seen on orthogonal image planes (not shown) and caused
contour abnormality of ventricular margin. Patient was counseled that these
findings likely were subependymal tubers but that specificity of these
findings was unknown. Patient elected to terminate pregnancy. No autopsy was
performed.
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Discussion
The underlying brain lesions of tuberous sclerosis are subependymal nodules
and cortical tubers. Subependymal nodules are situated at the edges of the
lateral ventricles. The subependymal nodules of tuberous sclerosis have been
detected in a preterm fetus as early as at 28 weeks' gestational age
[8]. The prenatal visualization
of tubers has been reported by Sonigo et al.
[6] in the third trimester in
fetuses with sonographically detected cardiac rhabdomyomas. In their study,
the researchers sedated the pregnant women to decrease fetal motion, and they
used T1-weighted imaging. In our patients, we did not use sedation, and we
used T2-weighted imaging. The tubers appear dark on this sequence either
because of magnetic susceptibility artifacts (from calcification) and/or low
concentration of mobile water. The tubers stand out on the T2-weighted images
because they are adjacent to the bright signal of water in the cerebrospinal
fluid spaces. To avoid confusing these lesions with artifacts, we set our
criteria for subependymal lesions to be seen on at least two scanning
sequences in orthogonal planes and to cause a contour deformity of the
ventricular wall. Multiplicity of lesions increases the likelihood that
tuberous sclerosis is the cause of the lesions.
Although in the two patients reported here, the prenatal diagnosis of
tuberous sclerosis was suggested on the basis of the cardiac findings of
rhabdomyomas, the finding of cortical tubers at such an early gestational age
has not previously been possible. Use of the ultrafast MR technique of HASTE
allowed prenatal visualization of cortical tubers without maternal or fetal
sedation. Because cortical tubers are more common than cardiac rhabdomyomas
and because cardiac rhabdomyomas are not frequently visualized on sonography
until the third trimester, it is possible that MR imaging combined with
sonography would allow improved prenatal diagnosis of tuberous sclerosis
complex. Further studies will be needed to determine the sensitivity and
specificity of prenatal MR imaging for screening for tuberous sclerosis
complex.
References
-
van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of
the tuberous sclerosis gene TSC1 on chromosome 9q34.
Science
1997;277:805
-808[Abstract/Free Full Text]
-
The European Chromosome 16 Tuberous Sclerosis Consortium.
Identification and characterization of the tuberous sclerosis gene on
chromosome 16. Cell
1993;75:1305
-1315[Medline]
-
Crawford DC, Garett C, Tynan M, Neville BG, Allan LD. Cardiac
rhabdomyomata as a marker for the antenatal detection of tuberous sclerosis.
J Med Genet
1983;20:303
-312[Abstract]
-
Wallace G, Smith FIC, Watson GH, Rimmer S, D'Souza SW. Tuberous
sclerosis presenting with fetal and neonatal cardiac tumors. Arch
Dis Child 1990;65:377
-379[Abstract]
-
Christophe C, Bartholome J, Blum D, et al. Neonatal tuberous
sclerosis: US, CT and MRI diagnosis of brain and cardiac lesions.
Pediatr Radiol
1989;6:446
-448
-
Sonigo P, Elmaleh A, Fennont L, Delezoide AL, Mirlesse V, Brunelle
F. Prenatal MRI diagnosis of fetal cerebral tuberous sclerosis.
Pediatr Radiol
1996;26:1
-4[Medline]
-
Bass JL, Breningstall GN, Swaiman KF. Echocardiographic incidence
of cardiac rhabomyoma in tuberous sclerosis. Am J
Cardiol 1985;55:1379
-1382[Medline]
-
Sharp D, Robertson DM. Tuberous sclerosis in one infant of 28
weeks' gestational age. Can J Neurol Sci
1983;10:59
-62[Medline]
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Introduction
Case Report
