Cebocephaly in an infant with trisomy 18

Abstract

An infant who died in the perinatal period with the unusual association of trisomy 18 and cebocephaly is described. It is suggested that this association may be more common than is generally recognised because the majority of such infants are stillborn or live only briefly and often do not have chromosome studies performed.

Full text

Case
reports
Cebocephaly
in
an
infant
with
trisomy
18
SUMMARY
An
infant
who
died
in
the
perinatal
period
with
the
unusual
association
of
trisomy
18
and
cebocephaly
is
described.
It
is
suggested
that
this
association
may
be
more
common
than
is
generally
recognised
because
the
majority
of
such
infants
are
stillborn
or
live
only
briefly
and
often
do
not
have
chromosome
studies
per-
formed.
Cebocephaly
is
an
aetiologically
heterogeneous
malformation
complex
whose
association
with
tri-
somy
13
and
the
18p-,r(18)
deletion
syndrome
is
well
established,
but
which
is
distinctly
uncommon
in
trisomy
18
(Lazjuk
et
al.,
1976).
In
this
paper
we
describe
an
infant
with
trisomy
18
who
had
cebo-
cephaly,
and
suggest
that
malformations
of
the
arrhinencephaly-holoprosencephaly
type
may
be
more
common
than
is
generally believed
in
trisomy
18.
Case
report
This
boy
was
the
third-born
child
of
a
healthy
28-
year-old
mother
and
30-year-old
father.
He
was
born
after
36
weeks'
gestation
weighing
1110
g
and
was
pronounced
dead
at
15
minutes
of
age.
The
occipito-frontal
circumference
was
23
cm,
length
37
cm,
and
chest
circumference
21
cm.
The
eyes
were
close
set
and
prominent;
the
nasal
bridge
low
and
the
nose
was
small
with
a
single
nostril
(Fig.
1).
The
chin
was
flat,
and
the
neck
short
and
webbed.
The
testes
were
undescended
and
there
was
a
glandular
hypo-
spadias.
Major
necropsy
findings
included:
lack
of
division
between
the
cerebral
hemispheres
with
absence
of
the
frontal
lobes,
olfatory
bulbs,
and
tracts,
Type
I
tracheoesophageal
fistula,
a
ventricular
septal
defect,
an
extralobar
sequestration
of
the
left
lung
supplied
by
a
subdiaphragmatic
intercostal
artery
and
draining
into
the
azygous
vein,
a
Meckel's
diverti-
culum
containing
heterotopic
gastric
mucosa
and
pancreatic
tissue,
and
a
single
umbilical
artery.
Microscopical
studies,
in
addition,
showed
un-
explained
focal
medial
calcification
and
intimal
thickening
of
the
arteries
of
the
neck,
and
prominent
lymphoid
aggregates
in
the
lungs,
kidneys,
pancreas,
and
lymph
nodes.
Q-banded
chromosome
analysis
of
20
cells
grown
from
a
postmortem
skin
biopsy
showed
trisomy
18
in
all
cells
(Fig.
2).
291
Fig.
1
Postmortem
photograph
of
infant,
illustrating
cebocephaly
and
hypoplastic
external
genitalia.
Fig.
2
Q-banded
karyotype
ofpatient
showing
trisomny
18.
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292
Discussion
The
small
size
for
dates,
cardiac
and
oesophageal
defects
observed
in
our
patient
are
commonly
seen
in
trisomy
18;
however,
the
infant
reported
by
Holmes
et
al.
(1974)
is
the
only
other
case
of
cebocephaly
associated
with
trisomy
E
(presumed
18)
of
which
we
are
aware.
In
a
recent
discussion
of
the
genetic
hetero-
geneity
of
cebocephaly,
Lazjuk
et
al.
(1976)
stated
that
this
case
was
the
only
such
association
in
over
400
reports
of
trisomy
18
and
suggested
that
it
may
have
represented
a
chance
occurrence.
It
has
been
pointed
out
by
Machin
and
Crolla
(1974),
Sutherland
et
al.
(1974),
and
Kuleshov
(1976)
that
a
significant
proportion
of
children
with
trisomy
18
are
either
stillborn
or
die
in
the
immediate
peri-
natal
period.
Though
some
of
these
infants
have
recognisable
features
of
Edwards
syndrome,
Machin
and
Crolla
(1974)
emphasised
that
those
who
are
stillborn
or
who
die
in
the
perinatal
period
represent
the
severe
end
of
the
spectrum
of
malformations
associated
with
trisomy
18,
are
often
macerated,
and
frequently
do
not
have
chromosome
studies
per-
formed
and,
therefore,
remain
undiagnosed.
It
is
of
note
that
2
of
the
8
infants
reported
by
Machin
and
Crolla
(1974)
had
cerebral
holospheres,
and
though
neither
of
these
infants
had
cebocephaly
(G.
A.
Machin,
1976,
personal
communication),
there
is
a
consensus
that
cebocephaly
is
part
of
a
spectrum
of
malformations
with
the
same
morphogenesis,
ranging
from
defects
in
the
prolabium
and
premaxilla
to
cyclopia
(DeMyer,
1975).
It
is
possible
that
patients
with
trisomy-
18
and
cebocephaly
are
relatively
under-represented
in
reported
series
of
patients
with
trisomy
18
as
they
tend
to
be
stillborn
or
die
in
the
perinatal
period
and
are
less
likely
to
have
chromo-
some
studies
performed.
We
would
like
to
thank
Mrs
Dianne
Tucker,
R.
T.,
Case
reports
for
her
technical
work,
and
Dr
E.
R.
Jorundson
who
referred
the
baby
for
pathological
studies.
ALASDAIR
G.
W.
HUNTER,
MANORANJAN
RAY,
AND
CLAIRE
LANGSTON
Division
of
Genetics,
Departments
of
Pediatrics
and
Pathology,
University
of
Manitoba
and
Health
Sciences
Centre,
Winnipeg,
Canada
References
DeMyer,
W.
(1975).
Median
facial
malformations
and
their
implications
for
brain
malformations.
Birth
Defects:
Original
Article
Series,
Vol.
XI,
7,
155-181.
Holmes,
L.
B.,
Driscoll,
S.,
and
Atkins,
L.
(1974).
Genetic
heterogeneity
of
cebocephaly.
Journal
of
Medical
Genetics,
11,
3540.
Kuleshov,
N.
P.
(1976).
Chromosome
anomalies
of
infants
dying
during
the
perinatal
period
and
premature
newborn.
Human
Genetics,
31,
151-160.
Lazjuk,
G.
I.,
Lurie,
I.
W.,
and
Nedzved,
M.
K.
(1976).
Further
studies
on
the
genetic
heterogeneity
of
cebocephaly.
Journal
of
Medical
Genetics,
13,
314-318.
Machin,
G.
A.,
and
Crolla,
J.
A.
(1974).
Chromosome
con-
stitution
of
500
infants
dying
during
the
perinatal
period.
Humangenetik,
23,
183-198.
Sutherland,
G.
R.,
Bauld,
R.,
and
Bain,
A.
D.
(1974).
Chromo-
some
abnormality
and
perinatal
death.
Lancet,
1,
752.
Requests
for
reprints
to
Dr
A.
Hunter,
Department
of
Genetics,
Health
Sciences
Centre,
700
William
Avenue,
Winnipeg,
Canada
R3E
OWI.
Addendum
After
acceptance
of
this
paper
for
publication,
a
report
appeared
by
Lang
et
al.
(1976)
of
a
stillborn
infant
with
trisomy
18
and
cyclopia.
This
report
adds
weight
to
our
contention
that
a
significant
proportion
of
infants
with
trisomy
18
and
malformations
of
the
arrhinencephaly
type
may
go
undiagnosed
because
of
failure
to
carry
out
chromosome
studies.
Reference
Lang,
A.
P.,
Schlager,
F.
M.,
and
Gardner,
H.
A.
(1976).
Trisomy
18
and
cyclopia.
Teratology,
14,
195-204.
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doi: 10.1136/jmg.14.4.291
1977 14: 291-292J Med Genet
A G Hunter, M Ray and C Langston
trisomy 18.
Cebocephaly in an infant with
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