Schizencephaly: Case
Report of Familial
Incidence

[ 10,11 ]. The incidence was 1:1,650 in patients examined
by computed tomography (CT) in one study and is invariably a sporadic event without familial recurrence [12].
There is one case report of siblings with schizencephaly
[13]. We report two half-siblings both of whom have been
diagnosed as having schizencephaly.
Case Reports

Mark A. Hosley, MD*,
I s r a e l F. A b r o m s , M D t , a n d
R o n a l d L. R a g l a n d , M D *

Two half-siblings with schizencephaly are presented.
They have the same mother who had a normal cerebral
imaging study. Only one other kindred was found in
which 2 siblings had this cerebral lesion. In the present
patients, autosomal inheritance from the mother is possible, but other explanations should include familial, as
well as genetic, factors. Family counseling should stress
the sporadic nature of this entity but a recurrence in
the same sibship is possible. Details of the clinical and
magnetic resonance imaging studies are presented.
Hosley MA, Abroms IF, Ragland RL. Schizencephaly:
Case report of familial incidence. Pediatr Neurol 1992;8:
148-50.

Introduction
Schizencephaly is a term first used by Yakovlev and
Wadsworth [1,2] to characterize a developmental defect
previously described by Kundrat [3] and Wilmarth [4] as
"symmetric clefts in the cerebral mantle during neuronal
migration." Yakovlev and Wadsworth categorized schizencephaly clefts as having fused lips (Type I) or unfused lips
accompanied by hydrocephalus (Type II) [2]. With the
advent of magnetic resonance imaging (MRI), this abnormality has been more widely recognized. The defect is
generally found in the region of the Rolandic fissure and
is frequently associated with local pachygyria, polymicrogyria, or lissencephaly. Gray matter heterotopia, absence
of the septum pellucidum, and hypoplasia of the optic
nerves have also been associated with schizencephaly [57]. The concurrence of schizencephaly with septo-optic
dysplasia may represent a common etiology occurring at
30-60 days of gestation [7-9]. Clinically, schizencephaly
is associated with intellectual retardation, epilepsy, microcephaly, generalized spasticity, hypertonia, or hypotonia

From the Departments of *Neurology, tPediatrics, and :~Radiology;
University of Massachusetts Medical Center; Worcester,
Massachusetts.

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The two patients are hall-siblings, genetically related through their
mother, each of whom has a clinically normal full-brother. The two
fathers are not related.
Patient I. This patient, a 15-year-old female, is the older hall=sister
of Patient 2. She was the product of a spontaneous vaginal delivery at
51/2 weeks past the mother's due date. The pregnancy was uneventful
but the mother drank 1-2 glasses of wine periodically during this gestation. She did not smoke, report any illnesses, or take drugs during the
pregnancy. Soon after birth our patient had been diagnosed as having
suffered a "stroke" because of left-sided weakness. The patient, however, has reached normal developmental milestones, achieved average
or above average grades in school, been active in sports, and has a
mild left hemiparesis. She was admitted to our service because of the
onset of generalized clonic seizures at age 15 years. The examination
revealed normal mental status and signs of mild spastic left hemiparesis. Her waking electroencephalogram (EEG) was normal 2 weeks
later. Her seizures are controlled by carbamazepine.
Neuroradioh)gy. Unenhanced CT revealed a unilateral right hemispheric schizencephaly, generalized mild to moderate veutricular enlargement, and absence of the septum pellucidum (Figs I A, I B). Uneuhanced MRI was perlormed in the axial, coronal, and sagittal planes.
This study agam revealed unilateral, closed-lip, right hemispheric
schizencephaly (Fig 1C). The characteristic thickened gray matter lining of the schizencephalic cleft was best visualized on the axial second
echo T2 sequence. Further, an adjacent periventricular gray matter heterotopia was clearly identified. Again, ventricular prominence and absence of the septum pellucidum were observed.
Patient 2. This patient is the 13-year-old half-brother of Patient I,
diagnosed as having m{xlerate asymmetric (right predominant) quadriparetic "cerebral palsy" at 1 year of age. The patient was born after a
44 week gestation complicated only by vaginal spotting during the last
week. Again, the mother drank I-2 glasses of wine occasionally during
the pregnancy, but she took no drugs, had no illnesses, and did not
smoke. Cesarean section was required following failure of induction of
labor and fetal bradycardia after 14 hours of labor. Birth weight was
4.5 kg. The patient had significant developmental delays, moderate
mental retardation, and diagnosis of a seizure disorder at 2 years of
age. The seizures were generalized chmic, more marked on the right
side, well-controlled on combined therapy of valproic acid and carbamazepine. This patient is currently in a 5-pupil classroom, receives ongoing occupational and physical therapy, and takes adaptive physical
education. He had a surgical lengthening of the right Achilles tendon at
age 2 years. A recent EEG demonstrated poorly developed background
rhythms with frontal intermittent rhythmic theta and delta activity.
Family history revealed a 36-year-old mother with a normal neurologic examination and a normal cranial MRI. The maternal grandmother died secondary to a rupture of a cerebral aneurysm at age 56
years and a first cousin of the mother required clipping of a cerebral
aneurysm. The mother of our patients has 4 normal siblings and both
husbands have 2 and 5 siblings, respectively, all of whom are neurologically normal.

Communications should be addressed to:
Dr. Abroms; University of Massachusetts Medical Center;
Department of Pediatrics; 55 Lake Avenue North;
Worcester, MA 01655.
Received July 18, 1991; accepted November 13, 1991.

A

B

C

Figure 1. Patient 1. (A) Axial CT at the ventricular bodies reveals a unilateral right-sided schizencephaly of the closed-lip variety. There is
subtle high density (gray matter density) that lines the schizencephalic cleft (arrows). (B) Axial CT at the frontal horns reveals an absence of the
septum pellucidum. (C) Axial second echo T2 MRI at the level of the ventricular bodies again discloses the unilateral right-sided schizencephalic
cleft which is lined by gray matter intensity (open arrows). An arrowhead has been placed on a focus of heterotopic periventricular gray matter.
Neuroradiology. The CT and MRI results of Patient 2 disclosed more
severe abnormalities which correlated with his greater degree of functional impairment. Unenhanced CT performed in the axial plane revealed bilateral schizencephalic defects. The right-sided defect was
smaller and of the closed-lip variety and the larger left-sided schizencephalic defect was the opened-lip type. As in the older sibling, there
was absence of the septum pellucidum. There is also marked focal enlargement of the left ventricular body and frontal horn. On MRI, the
second echo T2 sequence demonstrated abnormal gray matter lining the
schizencephalic clefts (Figs 2A-2C).

Discussion
Prior to the n e u r o i m a g i n g technology n o w available,
schizencephaly was a rare diagnosis m a d e at autopsy [ 12];
however, with the advent o f intrauterine ultrasound imag-

A

B

ing of the brain, as well as C T and M R I after birth, the
recorded i n c i d e n c e has dramatically increased [14-16].
This report is the first to present the only k n o w n half-siblings with s c h i z e n c e p h a l y and, to our k n o w l e d g e , the
second instance of familial occurrence of schizencephaly
[13]. Because the two patients were genetically related
only through their mother - who is neurologically n o r m a l
and has a n o r m a l cranial M R I - the mode of inheritance is
possibly autosomal dominant; a cytosomal mitochondrial
defect is highly unlikely because two other children o f this
mother are normal. Autosomal recessive inheritance is also
possible but the two fathers were not related. Sex-linked
inheritance is unlikely because of the first patient's being
a female. O n e c a n n o t exclude nongenetic, familial, or en-

C

Figure 2. Patient 2. (A) Axial CT at the ventricular bodies demonstrates a smaller right hemispheric closed-lip schizencephaly (arrows) and a
larger left hemispheric opened-lip schizencephaly (arrows). (B) Axial second echo T2 MRI at the ventricular bodies demonstrates to better
advantage the gray matter lining of the bilateral schizencephalic clefts (arrows). (C) Coronal 7"1 MRI through the frontal horns reveals the
gaping left hemispheric cleft (arrows) as well as an absence of the septum pellucidum and focal dilatation of the left frontal horn ventricular body.

Hosley et al: Schizencephaly 149

vironmental causes, such as intrauterine infection or a
toxic etiology, but no local uterine abnormality was present to explain these cerebral lesions.
There are two theories concerning the pathogenesis of
schizencephaly. The first, proposed by Yakovlev and
Wadsworth, suggests a localized failure of induction of
neuronal migration from the ependymal cells lining the
primitive ventricle before the time of primary sulcation
which would have to occur between 30-60 days of gestation [7-9] and can be unilateral and asymmetric [5,8,12].
The second theory proposes an early destructive lesion
involving this segment of the hemisphere, perhaps due to
a localized vascular occlusion, followed by disordered and
excessive cortical overgrowth; therefore, this process
would lead to a limited destructive porencephaly [17].
A familial incidence of congenital porencephaly itself
has been described, but is rare [18]. This entity is believed
to be due to a destructive encephalopathy in most instances
rather than a marked hemispheral dysgenesis.
Encountered at our own institution are several cases of
schizencephaly associated with septo-optic hypoplasia
(Demorsier's syndrome) and several reports confirm this
association [7-9,19]. The latter entity is very rarely familial
[20] and may also be due to a destructive process [21].
In view of this report, families with a child with schizencephaly should be advised that although most cases ate
sporadic in occurrence, rarely, a second child may also
have this cerebral lesion. Furthermore, the etiology could
be familial or environmental yet not genetic in origin.
Similar advice may be pertinent with the entities of congenital porencephaly and septo-optic hypoplasia.

We would like to express our gratitude to Beth A. Ellis for secretarial
support and patience during the preparation of this manuscript.

References

[l] Yakovlev P1, Wadsworth RC. Schizencephalies: A study of the
congenital clefts in the cerebral mantle, I. Clefts with fused lips. J
Neuropathol Exp Neurol 1946;5:116-30.

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[2l Yakovlev P1, Wadsworth RC. Schizencephalies: A study of congenital clefts in the cerebral mantle, II. Clefts with hydrocephalus and
lips separated. J Neuropathol Exp Neurol 1946;5:169-206.
13] Knndrat H. Die porencephalie. Eine anatomische studie. Graz:
Lenschuss & Lubensky, 1882;8:1-126.
[4l Wilmarth WA. Presentation to the Philadelphia Neurological
Society. J Nerv Ment Dis 1887;14:395-407.
[5] Bird CR, Gilles FH. Type l schizencephaly: CT and neuropathologic findings. AJNR 1987;8:451-4.
[6] Jacobson M. Developmental neurobiology. New York: Plenum
Press, 1978;57-114.
[7l Marchal G, Andermann F, Tampieri D, et al. Generalized cortical dysplasia manifested by diffusely thick cerebral cortex. Arch
Neurol 1989;46:430-4.
[8] Barkovich A J, Norman D. MR imaging of schizencephaly.
AJNR 1982;9:297-302.
[9] Chamberlain MC, Press GA, Bejar RF. Neonatal schizencephaly: Comparison of brain imaging. Pediatr Neurol 1990;6:382-7.
[10] Miller GM, Stears JC, Guggeuheim MA, Wilkening GN. The
clinical and computerized tomographic spectrum of schizencephaly in
six patients. Neurology 1982;32:A218-9.
lll] Aniskiewlez AS, Frumkin NL, Brady DE, Moore JB, Pera A.
Magnetic resonance imaging and neurobehavioral correlates in schizencephaly. Arch Neurol 1990;47:91 I-6.
[12] Miller GM, Stears JC. Guggenheim MA, Wilkening GN.
Schizencephaly: A clinical and CT study. Neurology 1984;34:
997-1001.
[13] Tilton AH, Krywanio M, Greene C, Nadell JM, Posas H.
Schizencephaly: Familial occurrence. Neurology 1988;38(Suppl 1):398.
[14] Byrd SE, Osborn RE, Bohan TP, Naidich TP. The CT and MR
evaluation of migrational disorders of the brain, part I. Lissencephaly
and pachygyria. Pediatr Radiol 1989; 19:151-6.
[15] Klingensmith WC llI, Cioffi-Ragan DT. Schizencephaly:
Diagnosis and progression in utero. Radiology 1986;159:617-8.
llr] Lituania M, Pussamonti U, Cordone MS, Magnano GM, Toma
P. Schizencephaly: Prenatal diagnosis by computed sonography and
magnetic resonance imaging. Prenat Diagn 1989;9:649-55.
[17l Lyon G, Evrard P. Neuropaediatrie. Paris: Masson, 1987;54-7.
[18] Gross H, Simanyi M. Porencephaly. In: Vinken PJ, Bruyn GW,
eds. Handbook of clinical neurology. Amsterdam: Elsevier/North Holland, 1977:30:681-92.
[19] Barkovich AJ, Norman D. Absence of the septum pellucidum:
A useful sign in the diagnosis of congenital brain malformations. Am J
Roentgenol 1989;152:353-60.
[20] Benner JD, Preslan MW, Gratz E, Joslyn J, Schwartz M,
Kelman S. Septo-optic dysplasia in two siblings. Am J Ophthalmol
1990; 109:632-7.
[21] Landrieu P, Evrard P. La dysplasie septo-optique: Etud6 clinique et elements d'un conseil genetique. J Genet Hum 1979;27:329-41.