Walker-Warburg Syndrome
By:
Terry J. DuBose, M.S., RDMS, FAIUM,
Director, Diagnostic Medical Sonography
Harold B. Collins, M.D., Department of Obstetrics & Gynecology
Barbara A. Karczeski, M.S., CGC, Arkansas Reproductive Genetics Program
University of Arkansas for Medical Sciences
Little Rock, Arkansas, USA
Case Study:
This is a case of a 19-year-old female referred to the high-risk obstetrical laboratory for evaluation because
of an abnormal sonogram that indicated cerebral ventriculomegaly. A series of sonographic examinations were performed
over a three-month period. The current case will focus on the images of the third examination; however, the age
range analysis will use the results of four examinations for comparison. A Certified Genetics Counselor (BAK) met
with the patient prior to and after the examination.
The current examination was performed at 31.1 weeks after the reported LMP by a registered sonographer (TJD)
using modern equipment. The transducer used was a curvilinear with selectable 3.5 or 4.0 MHz frequencies. A complete
examination was done, producing multiple planes of view of the major organs. The sonographic images were of a good
quality and the examination was considered diagnostic.
The physician's (HBC) review of the images found hydrocephaly with an abnormal cranium. The cephalic measurements
were considered relatively enlarged. Images of the posterior fossa demonstrated dysgenesis of the cerebellar vermis,
suggesting a Dandy-Walker malformation. No other anomalies were seen on this examination. The amniotic fluid was
normal.
The baby was delivered by C-section at the UAMS hospital due to hydrocephaly on September 15, 1997, a gestational
age of approximately 36.6 weeks by LMP or 39.5 weeks by the 1st sonographic examination. The neonate was admitted
to the Arkansas Children's Hospital. Postnatally, this baby was diagnosed with Walker-Warburg, a relatively rare
autosomal recessive disorder. Clinical features present in this child included microphthalmia, lissencephaly, agenesis
of the corpus callosum, vermian hypoplasia, and a possible Dandy-Walker variant. The family was counseled about
the poor long-term prognosis and the recurrence risk of 25% in each pregnancy. Prenatal diagnosis is limited to
ultrasound evaluation, as a specific gene defect has not yet been identified. Prenatal genetic testing may be available
in the future on a research basis for these families.
Discussion:
Dandy-Walker malformations (DWM) are reported to have an incidence of one out of 25,000 to 35,000 cases, and
are present in approximately four percent of cases with hydrocephalus.1 Others have reported that in
pediatric cases hydrocephalus is associated with DWM in 13% of the cases.2 DWM covers a spectrum of
abnormalities of the cerebellum that range from an increased indentation of the cerebellar vermis to complete agenesis
of the vermis with a deep cleft between the hemispheres of the cerebellum. This cleft between the hemispheres represents
enlargement of the 4th ventricle, is filled with spinal fluid, and is often referred to as a Dandy-Walker cyst.
3
This case provides a good example of a Dandy-Walker malformation with hydrocephalus. It also demonstrates the
effects of hydrocephalus on fetal parameter size.
Above: Posterior fossa image, Dandy-Walker malformation of the cerebellum. A similar view of a normal cerebellum
(not this case) is included for comparison.
Above: Transverse and coronal planes of the fetal head: hydrocephaly.
Above: Four chamber fetal heart and M-mode heart rate:
Above: Coronal view of the fetal abdomen: Normal bladder, stomach, liver and heart positions.
Above: Transverse view of the fetal abdomen demonstrating kidneys and femoral diaphysis measurement.
Fetal growth and age range analysis:
The following discussion is a presentation of the use of parameter age range analysis (ARA)
to analyze fetal growth and the relative proportions of the fetal parameters.4 Many do this intuitively
by comparing the fetal age estimated by sonography to the expected age, but this discussion will present the use
of this method to evaluate fetal parameter proportions. In these images the fetal parameters are represented by
alphabetic symbols in the time-series histogram: M=LMP, B=BPD, T= transverse head circumference, C=coronal head
circumference, V=cranial volume, >=coronal triangle circumference, F=femur, a=abdominal circumference, A=average
ages of all parameters, and b=average ages of all brain (cranial) parameters.5, 6,7
The use of the coronal view of the fetal head and the VCD allows a three dimensional evaluation of the fetal
skull. The change in size of the 3D head and the use of the ARA to view the relative proportions of the parameters
is particularly useful in cases of hydrocephaly or other head shapes and molding.. The following images help clarify
these concepts.7
Above: Using a software package (BASIC BABY ©) to examine the
ARA in the time-series symbolic distribution (across the bottom of the screen) it can be observed that in examination
#3 the parameters of the fetal head cluster between 36.5 and 38.3 weeks, with the cranial volume (V) and the coronal
head circumference (C) leading. These are the only two head parameters that include the vertical cranial diameter
(VCD). The abdominal circumference (a) is at 31.8 weeks, and the femur is at 33.3 weeks.
Above: By taking the ARA data and cutting out only the symbolic time-series distributions and lining them up
week by week the growth and increasing distribution of the parameters size/ages can be easily observed. Note that
the abdominal circumference (a) and the femur length (F) are approximately 2.7 weeks in advance of the LMP age
(M) in examination #1, but by the 4th examination they are only about 1.6 weeks in advance of the LMP. This lag
in body growth of one week may be indicative of some degree of IUGR. During the same period the head parameters
moved from approximately 2.6 weeks (1st examination) to 3.9 weeks (4th exam) in advance of the LMP age. This acceleration
in head size is attributed to the effects of hydrocephalus. It is also noted that the BB software program does
not calculate parameter ages beyond 41 weeks, and in this case (Exam #4) the transverse head circumference (T)
is beyond 41 weeks and is shown as "T+" arbitrarily at 42 weeks in the time-series.
Above: Another way of looking at this same data is to line up the LMP ages (vertical dotted line left of "M")
and observe the relative positions of the fetal parameter's size/ages. The lagging in body growth and acceleration
of the head size is again observed.
Acknowledgments:
The authors wish to acknowledge the contribution of the sonographers who performed these examinations:
Exam #1 Lisa C. Eddins, A.S., RDMS, RT(R)
Exam #2 Kristi Brewer, B.S., RDMS, RVT, RT(R)
Exam #3 Terry J. DuBose, M.S., RDMS, RT(R)
Exam #4 Mandi Graham, B.S., RDMS, RT(R)
Disclaimer: One of the authors (TJD) is the author and owner of the software BASIC
BABY, and therefore acknowledges a financial interest. This interest is mitigated in that BB is an old DOS
program that is no longer advertised except on the author's personal WWWeb
pages.
References:
1. Sanders R C: STRUCTURAL FETAL ABNORMALITIES, The Total Picture. Mosby, 1966; p. 27.
2. Fleischer A C, Romero R, Manning F A, et al: ULTRASONOGRAPHY in OBSTETRICS and GYNECOLOGY, The Principles
& Practice of; Appleton & Lange, 1991; p. 213.
3. Filly R A, Ultrasound Evaluation of the Fetal Neural Axis, in Callen P: ULTRASONOGRAPHY in OBSTETRICS and
GYNECOLOGY, 3rd edition; W. B. Saunders Co, 1994; p. 192-195.
4. DuBose TJ, Poole E, Butschek C, et al: Range of Multiple Fetal Parameters. Official Proceedings 1988 World
Federation for Ultrasound in Medicine and Biology; J Ultrasound Med, 1988; 7:S205-206.
5. DuBose TJ; "FETAL BIOMETRY: Vertical Calvarial Diameter and Calvarial Volume"; J Diagnostic Medical
Sonography, 1985; 1:205-217.
6. DuBose TJ; Assessment of Fetal Age and Size: Techniques & Criteria: in Berman MC, Editor; Obstetrics
& Gynecology: Diagnostic Medical Sonography, A Guide to Clinical Practice, Vol. 2; JB Lippincott ,1998.
7. DuBose TJ; FETAL SONOGRAPHY. W. B. Saunders Co., 1998; p. 95-199.
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