THE

FACE

PREDICTS THE BRAIN: DIAGNOSTIC
SIGNIFICANCE
OF MEDIAN
FACIAL ANOMALIES
FOR
HOLOPROSENCEPHALY
(ARHINENCEPHALY)

William

DeMyer,

M.D.,

of

Neurology,

Departments

Wolfgang
Indiana

the

MONG

more

anomalies

specific
or

of

Facial

some

ism
Table

I. The

lies

appear

median

in

patterns

or

cebocephaly,

most
diet

as

a glance,

a

severe,

When

the

sists

of

diagnosed
always

Type

Facial
Single

eye

orbit.

orbits.

III.

Cebocephaly

with

orbital
Arhinia

Orbital

IV.

With

cleft

median

lip

Orbital

into

or

olfactory

holistic,

as
and

lion-

bulbs,

it

a holoprosen-

more

holoprosencephahic

normal

end

spectrum,

in-

(Aimim INF:xeF:emm%Lv)

(‘ranluin
eye

in single

hypotelorisni

but

proboscis.

cleft

of lip

Brajit

Imoloprosemmcephmaly

Microceplmaly

separate

imoloprosenceplmaly

Alohar

proboscis-like

and

Microcephialy
Alobar

with

flat

into

tra nsversely

I

divided

bypotelorism,

prosencephsagitfaily

diencephalon,
amid

con-

presence-

the

or

optic

proboscis.

hypotelorism,

but no median

and

arrested

cleave

intermediate

the

the

malformed

members

Since

2

to

remain

cephalon.
In the

gradations,

of

Features

or )artially

Arhinia

Extreme

Ethmocephaly

into
to

of

Ph.D.

Program,

severely

normal

and

OF hloLom’nosEs(’EPmmALY

of Face

I. Cyclopia

II.

EES

the

hemispheres,

zontally

‘I’ABLE

I ) EGII

SEv:mtF:

various

degree

telencephalon

brain

its

may

tends

characteristic

Palmer,

Genetics

links

nearly

cerebral

alpre-

Medical

cleavage.1
fail

alon

combined

which
can be
these
facies

In

some

phalic

gra-

ethmocephaly,

highly

and

anoma-

cyclopia,

2

anomaly

de-

in

Gardella

the

indianapolis

eye

listed

related

Medicine,

brain

hypotelor-

as

lawfully

combinations.
such

at

orbital

facio-cerebral

in various

and

dations

of

a single

deformities

and

anomaly.1
by

facio-cerebral

degree

oronasal

of

congenital

include

Catherine

and

Medicine,

School

characterized

median

anomalies

lesser

and

M.D.,
and

University

grotesque

is a group

types

fects.

Zeman,

Neuropathology,

nose

Microcephaly.

Usually

has

alobar

holoprosemicephaly
nose.

ilidrocephmaly

ami(I soimiet imimes trigo-

mloce1)halv.

Usually

Imas alohar

imolo-

)rosence)lmaly.

V. With median
philtrumpremaxilla
Anlage

Orbital
of

iiypotelorismmi,

lip

with

l)ilateral

mnetliamm

philtrum-preniaxillary
This

each

table
category

presemits
are

five

remarkably

facies

diagnostic
similar

1)0CSS

lateral

Anlage.

Flat

of hmoloprosencephaly.

frommi patient

to patient.

cleft

representing

nose.

Altimough
The

two

(W.DeM.)

Indhana

University

‘sledical

Center,

1100

Iy 1111(1
Semnilohar

t rigo-

soiiittimiit’s

or lohar

liolo-

prosenceplmaly

tramisitiommal

patients

(Submitted
January
9; accepted
for publication
March
9, 1964.)
%V.DeM.
is Special
Fellow,
National
Institute
of Neurological
Diseases
Public
Health
Service
(NB18404).
C.G.P.
is Special
Fellow,
National
Institute
of Health
(GM 16518).
ADDRESS:

\Iicrocel)lma
mlocel)IhaIV.

West

iii timis

cases
report

do occur,
belong

audI

Blindmiess,

Michigan

Street,

time facies

Unitedl

Indianapolis

of

V.

in category

States

7,

Indiana.
PEDIATRICS,

256

Downloaded from by guest on September 23, 2016

August

1964

ARTICLES
sufficient

attention

patterns

has

facial

of

predictive

been

significance

paper,

based

scribes

a diagnostic

of an

given

anomalies

on

for
two

intermediate

the

their

brain.

This

cases,

de-

littleknown

stage

the

to

instructive
hut

to

and

257

facies

of holoprosenceph-

aly.

CASE
2a?ient

1

This

4-montll-old

after
mrhotller,

\vhi()

tranol

female

lha(l

(Enovid)

l)efore

the

for

had

the

and

suggests

the

The
weeks

I).ltie1t

murmilur.
seizimres,

imi

the

Iler

4

no

the

and

drug
last

COUldI

trimester,

\Otml(l

l)eriO(1i-

which

movdmud’nts,

intratmterine

began

seizures.

to have

as

nlan\’

20

or

the

Ofl

months,

left

was

gained

she

flat

onl

to

8(X)

I ler

some

with

gm

left

sidle

larv

a

HISTORY:

Of 7 known
abortion

pregnancies,
at

\Vith

about

tile

hadi

hadi

tIm

mothd’r

left

foot

disclosed
dl111l

toe

toirhance.

the right.

sil)hmigs

he

(lenied

left

Her

oI(lest

fathd’r

and

leg.

11cr

age

of

5

diagnosedi

next

reported

boy,

an’
TIle

father,

the

iris,

her
23
with

whether

Of

andi

these

4

die(1
infants

The
had

siblings,
neonatallv.
were

wllere

the

2

were
Fle

malformiied.

Other-

by

l)hlVsical

born

premauncertain
The

other

The

anterior

a

finger

tip.

to

light,
were

of

and

hadi
optic

vhicli
She

wall

it was

imnitedi.

a stimulus.

giving

she

and

fronl

fed

when

mouth

Relaxed

other

the

chiseled

a Herculean

the

Downloaded from by guest on September 23, 2016

the

uvula,

be traced

pharynx,

with

were

stim-

the direction
awake

be
in

she

picked

stone.

and

near

continued1

lips

asleep,

2.

region

un-united

could

could

appearance.

the

normal

her

fromli

had

downward

towardl

when
She

tiewhite,

1 and

process

of

and headi resisted
movement
muscles
were
all visibly
her

back

and

her

rigidlity.
were

Figures

median

posterior

a statue-like
ties

The

size,

She

in
of

ad-

in

very

representing

the

turned

andl

or

were

hung

septum

and

coloboma

region

nasal

sucked

flat

normal

discs

processes

uvula.

the

cir-

transil-

unremarkable.

to) the

an

female

not

was

shown

apparently
the

did

were

no

was

occipitofrontal

fontanel

otherwise

lip

as
to

The

parents

white

head

Pupils

the

small

two

hack

though

The

patient

Her

extendled

impper

tmpward

of

normal.

Her

malformations

rnidlhine,

ulated,
COlOl)Omas

was

the

dieniedi

imiferiorlv.

detected

the

Anlage

a patent

I)ilateral

the

lip on the
A flat capilglabella
up-

the

The

cmii.

medliami

of

child,

mother

The

Oldl,

nialformations.

(lirectedi
ere

fundli
facial

foot

be

gm.

28

Although

the

a patent

having

reacted

the

at

living

fimial

as

had
old,

when

mittedi

no

astrocytoma,

autopsy

defect.

apex

smuall

died

and

forehead.

4-month-old

3,750
was

disthnn

8 years

weighed

feet.

Ilad
gait

a girl,

11cr

the

larger

cerehellar
at

diagnosed

ears
the

malformations

examimiation.

childi,

5 siblings

she

comigenitallv

foumid.

septal
of

no

is

and

a dlaughter

a

of

to

nourished,

luniinate.
of

mvotatic

noticeable

surgically.

EX.AMINATmON:

adle(uately
cumference

)regnancies

deflmutelv

a

amid
vas

imiterauricular

turely

had

from

arteriosus

a 5-year-oldl

s-as

oldest

ears

legs,
no

Child1,

also

surgicalh’

dimetus

wise

breast

gestation.

and

cleft

from
the

lip

representing

The

repaired
over

of

consanguinity.

who

spontaneous

hvpoplasia

tWo

had

01(1.

examinatiomi

strength

her

Slid

I-her

her

her

ill

signs.

amidi

that

but

process

extends
wardls

2

years

of

3 other

Phsical
congemiital

leg,

ere

extemisor

in

miiomith

\Vith

bleeding.

and

reflexes

second

Ilfldl

vaginal

26

median

been

hypotelorism,
cleft

and

a 24-hour

as

3 resulted

the

ahortiolls

she

mother

TIle

orbital

lateral

Anlage.

PHYSICAL

FAMILY

the

bilateral

hemangioma

51)’1m1.

of

1. Notice

bridge,

Psilate

tenperature

4 1 C vithin

nasal

1hiltrtmm-premtxillm

At
12
During

rel)aired.

progress.
34.5

on

drugs.

1. Patient

FIG.

generalized

more

anticomivimlsant

l)t\V((mi

took

2,900
gm
at birth.
Three
was
found
to have
a systolic
she

lii)

shortly

tIle
the

violent

(levelopmental

fluctuated

the

of

(if

cleft

first

iiii(le

as

51)ite

of

baby

6 S((k5

oftemi

days,
‘eeks,

Ildhlie

that

miles-

also

comiception

In

weighed
l)irth,
she

At

it

of
earl

make

Tl#{236}e

time

Dimming

1)Ossibihitv

after

stopped

bleedimig.

liOtiCd’(.l

stiffen

term

amldl

She

th(

vaginal

mother

cahly

niontlis,

the

l)Ut

full

norethvnodrel

3

1)0’ ascertaimiv(l.

mother

at
dleliverv.

###BOT_TEXT###’ls

(lurimig

gestatiomi,

born

breech

taken

l)1ti(’nt

traml(luilizers
not

was

unc()ml)hicatedl

aII

earl

REPORTS

Her
any

extremidirection.

palpably
She

had

up

made

tense,
little

as

258

FACE

AND

BRAIN
SUBSEQUENT

the

although
retained
cycle

imifant

she

took

most

of

seizures

gm.

per

She

6
at

the

interhemispheric
lobes,
only

and

of

1. This

trigomiocc)hlalv

ciliarv

view

aml(l

tile

The

(lepressiomis.

shows

a shgllt

again

super-

accomil)anvimig

of

flatness

the

nose

is

evid(’mit.

and!

ureter

vise

the

spontaneous
her

movememit,

range

elbow,

was

undler,

her

brisk,
flexion

slioved

no

handis

she

move,
as

hands

she

usually

She

had

failed

had

were

very
to

the

cerebri
olfactory

crista

galli
for

gastrointestinal

tract

left

but

not

renal
dilated.

ooas

\oeighed

pelvis
Other-

normal.

only

6

The
gui,

half

2
Negro

male,

delivery,

riodhic

a prom-

reflexes

responses

mal

The

tract

weight.

to

falx
of

4,

amid!

perforations

The

d!uphcated,

expected

This

folded

The
trace

no

and

malformations.

the

cavity
3

found.

genito-urinarv

Patient

the

heart,

proc’ss.

only

foulidi.

and!

single

cranial

in Figures

No

The

A

median

extended

be

weighed

cm.

the

fused.

be

together

3,95()

2 months.

32

the

shown

were

glands

were

thumbs

Nivotatic
and

triple

did
such

the

completely.

response.

exceedimigiv
strong,

with
her

fingers

she

joints,

2()-30#{176}. Her

to

opening

startle

when

major

clenchedl,

on

extend!

at

restricte(l

and

imient

and

motion

tightly

imsuallv

to

of

As

aolrenal
of

body

filled

could

were

to
several

medica-

in

gill

from

absent,

no

had
weighed!

was

could

tracts

lungs,

shiooved

degree

250

posteriorly.

nerves

The
Patient

she

fissure

completel’

continued

The

only

which

gm,

usually

of 8 months.

gm.

present

olfactory

2.

age

erupted

310

weighedi

and

anticonvu!sant
age,

completely

and1

was

FIG.

had!

brain

bulbs

formula

circumference

tooth

was

of

hospi-

200

41#{176}C. She

of

of

of

about

temperature

spite

the

a gain

occipitofrontal

frontal

her

EXAMmNATION:

gm,

The

on1

and

nionths

c!ied

incisor

of

Her

in

dhi\,

AUTOPSY

4,200

all

34.5

\Vhen

7 weeks

gained!

it.

between

tion.

During

COURSE:

talization,

horn

weigheol
he

cvamiosis,

respiratory

full

at

2,720
rd’(luired!

rhythm

terni

gm.

after

Because

oxvgeml

continued!

to

a norof

therap.

1)0

peIlis

irregular.

On

all

stereotyped,

p1antmr

stimiiula-

tion.
Slu’
pretedi

as

objects

comitrol

.

with

She

only

miormiial.

1 .0

fast

the

cm

to
1ei1s,

waves

arose

Iriplieral
tile
tured,
treate(l
aceto-orcein.

amid
with

or
head!

included
right

onlo

hand

blood

and

and

a

and!

range
be

no

20

froni

1)0th

in

the

Cells

from

karyotype,

chroniosomal

amiomiialies.

waves

in

activity

right-

spikes

low

higher

The

left-

and
amid!

sharp

a

:3.

FIG.

Holoprosencephiahic

fromital
skimi

biopsy

taken

l)roc(.ss

ap)ro)riate

chromosoirie

and

sides.

and

colchicine,

gahli.
of

slow

phiiltrmmii-premiiixi1la
after

cps

1-4

imidepemidemit

and

crista

mixture

arhvthniic

of

illdld’1)en(lent
J1i(l

count

showed!

a

rl#{236}vthms around

blood

miie(lian

no

the

I11)1rt

rhythmic

sided

fixate

had!

sllowed

frequency

tehldle(l

not

and

Roentgenograrns

Electroencephalograms

amiiplitude

could

Routine

RESULTS:

\vdre

voltage

inter-

indlicateci

hernia.

LABORATORY

urinalysis

in

be

that

eves

crd’ase

umbilical

coull
or

malformations

I)illm1i1r

orbits

that
adal)tive,

her

Extracephalic

a single
small

or

)rOgreS5.

developmental

fohlo\o

behavior

1)ur1)oseful

1)t’rio(!s
fixed,
both

and!
sources

without

fromii

of
stained!
showed
any

traced
the

ooere
growth
with
a 46
evident

vie\o.

the

fromii

poimit

The

braimi

b

gyms

undenieath
are

all

other

is
gvri

lobes

the

l)ros(mceI)h1Iihic
cleavage
this
I)oint
a vessel
(V)
as

fissure

temiiporo-occipital

indhicated

Patient

frormi

imlterh(misphlcric
arroovs,

forooard

ovhere

has !xcomiie
arrested!.
continues
veiitrallv,

comitinuous
on
fromital

Downloaded from by guest on September 23, 2016

the

across
orbital

lobe.

1,

can

the
surface

be
to

sagittal
but

From
the

nhidlhimid,
of

the

ARTICLES
one

occasion

iiiouthi

lie

FAMILY

l)and,

to

1-Ic
Old1,

clinically

110

I Icr

\o(re

1)0th

attemidimig
lhid

nu)ther

dlcmltl
(lied!

the

did!

not

One
of

his

had

a

lumbosacral

4 \odeks

of age.

ooere

marriage

her

husmonths

attrii)Imted

b

her

ahnoriiiahitv.
this

ovith

and

first
5

at

whether

back

amiol

The

amiomiialies.
h)

h)orn

hus-

health

1)hitdmittl

kmiow

Plrt
at

a

infant,

old.

amidl her

in good

i)eimig

to

mouth-to-

Stihhh)ormi

(l(atlL

PhYsician

malformneol.
loover

was

by
das

.35,

pregnamicics

(hii(l

age,

gestational

18

t congemiital

(‘\‘idl(n

first

revived!

mother,

h1Ldl 4 kmiowmi

anther

bamid.

be

(110(1 \ohiefl

The

HIsToRi:

:32

hia(l

had

respiration.

a

child
“cyst

p(lrill)zed!

was
on

legs”

re1)Orted

to

to

her

be

(fld!

2 cilildlremi

other

free

the
cvi-

mvelomeningocele
The

259

froni

of this

malforma-

tiomi.
\Vhiile

married

mother

has

iiai

5

current

llmmsband!,

p’gc#{128}’

She

living

children

1-2
months
of
amu! the
remaimider

\oerc

reported!

to

s1)m1t(1m1t’01s

The

7 knoovn

kimishiip

abortion

at

be

miomnial.

the

had!

1

gestation.
of this

Shld

denied!

consamiguinity.
PHYSICAL

life,

imifant

l)d,Camiie

tent.

On

EXAMINATION:

the

ap)eared!
whemi

cyanotic

his

cry

ooas

the

a(le(11iat(l\’
renioved
feeble

11th

from
amid

day

nourished.
his

of
He

oxygen

infrequent.

His

Fuc.

5.

Patient

shO\V5

tile

lateral

lateral

of the

cleft

facial

able,

2.
of

gestalt

inclU(ling

but

This

Iostmiiortem

Phi iltruni-premaxil

Patient

lip

in

2 has

amil

no

hint

occil)itofromital

ooas

not

transihluminate.
5.

Figure

of

the

directed

never

a(le(lUat(IV

lie

lie

moved

kept

all

his

t’xtremities
sive

or

mo(Ierately

triple

cmii.
his

anomalies
had!

an

iris

The

an-

hidadi

d!id

in

cmilobomi

with

Tue

fumndi

althoumgh
niost

of

increased
no

headl

he

The

to

Pusre-

reflexes

hia(!

very

response

in

timue.
righting

Myotatic

amid

reflexes

feebly.

tIm

resistance

showed!
reflexes.

brisk,

lid)

shown

are

extremities,

mild
lie

flexion

29

size.

clenchedi

rooting

nose,

visualized.

foumr

had

flat
and

inferomediahly.

hands

miiOV(m(hit.

flexes

ooas

nornial

eye

defect

ooere

of

right

and

trigomiocephalv

dlepressiomis.

Facial

The

hi-

similarity

1 aml(l 2 is imnmistak-

circmmmnferemuc

fontamiel

an(l

The

hivpotelorism

Sth1)ercihiar\

tenor

Amilage

pulitu.

Patiemits

orbital

photograph

ha

were

stereotyped!

to

1)lLntlr

stim-

ulation.

lie

had!

ami apical

genitalia

\ere

extremiiities

except

lII1(l a single

I)uthliiulr

4.

Iloloprosencephalic

o(’hitral

view.

failed!

to (‘Xtelidl

fromital

lobes,

absemit.
has

failed!

Sagittal
and

to

the

tracts

no

the

orbital

interhemispheric

horizontal
occur,

fromu

prosemic(phi1hic

arounc!

Because
to

brain

prosencepliilic
trace

cami

of
be

olfactory

foumid!.

Patient

1,
llas

cleavage

surface

of the
fissure

is

of
tory

and

plete

values

of

elevated!

cells

showed

halamice,

orbits

counts
osith

the
EEG

cultomres

a karvotype

failed
0.9

on
left

counts

gm/100

all
hand

cm

Downloaded from by guest on September 23, 2016

the

increased
in

infant’s

range

in

an

of

percemitiges
the

not

to grow.
apart
and

P’-

and!

differential

I)recariouls

could!
domie

showedl

ml
in

leukocytes
of

exto’rnal

(ligits
The

Bloodl

mm’,

an
skin

foot.

17-18

white

per

Becaumse

and!

left

his

six

crease.

polvmorphonuclear

cotmnt.
Blood!

cleavage

bulbs

18,000

the

STUDIES:

hemoglobin

Fid;.

nitmrmiiumr.
hinl

He

for

LABORATORY

sistently

cardiac

normal.

respira-

he

obtained!.

att&.mnpt

to comu-

Roentgenograms
no

crista

galhi.

FACE

260

AND

EXAMINATION
: The
brain
completely
cranial
cavity
but weighed
only 200 gm
(normal
weight
360 gm). It was virtually
identical
with the brain of Patient
1 in Figures
4 and 5. The
most
striking
external
feature
was
incomplete
sagittal cleavage
of the frontal
lobes.
The interhemispheric
fissure
stopped
at the frontal
pole rather
than continuing
on around
to the orbital
surface.

patients
differ,
prosencephalies

AUTOPSY

filled

No

the

trace

galli,

of

and

olfactory

no

bulbs

perforations

nients
present

were
found.
posteriorly,
cerebelli
with
the

and
for

tracts,

no

olfactory

tients

of the

haps

lies.

first

type.

heart
had
just below

arteriosus

an 0.5 cm interventricular
septal
the tricuspid
valve.
The ductus
patent.
The
right
lung
showed

was

bronchopneumonia.
The left kidney
kidney

had

an

weighed

extreme

and

a hydroureter.

the

ureter

Near

into

the

abruptly

diameter.

Histologically,

the dilated
was dilated
weighed

is 8.2
rotatedl,

gm

of entrance

bladder,

from

1.5

cm

the
to

time

of

lumen

0.2

cm

in

(normal

for

an

infant

2,700

gm

can

The
two

anomalies

were

bridge,

nasal

and

palate

senting

the

orbital

anomalies

and

bilateral

with

a median

lateral

trigonocephaly,

process

tients

flat

entiation

of

the

but

repreI

had a flat forehead.
The parallel
normalities
of the two infants
consisted
of
incomplete
sagittal
cleavage
of the cerebrum
and absence
of olfactory
bulbs
and
tracts, which we would
term
lobar
holoprosA.2 See
abnormalities

encepha!y

type

Physiologic

included

infants

and

apneic

or

uterine

any

growth

of

3 and
4.
one
or both

poikilothermia,

hyperreflexia
spells

Figures

triple

flexion

seizures,

intra-

retardation,

psychomotor
progress.
In spite of parallel
facio-cerebral

lies, the extracephalic

anomalies

lack

the

and

organogenetic
at

mandible,
the

any
too,

other

patients

facial
who

lower

the
of

in the two

tissue

prechordal
of mechaniterato-

originating

cleavages
on

stage
may

differ-

of
be

bones,

it

may

pros-

become

development.
affected,

The

along

as in some

showed

in it

of the

with

of Potter’s

micrognathia,1

or

in

animals.bo
Diagnosis
reviewing

literature

sonally
and

anoma-

the

When

dependent

arrested

only

as nervous

bones

the
pa-

to

environmental

midline

encephalon

rise

in these

because
or

exneu-

mesoderm.

not

is defective,
the

is

defective

“determines

ii

paper,

rostral

gives

the ectoderm
its morphology.”i

also

of this

a brief
embryologic
of median
facial

of

Upon

extra-

are

facio-cerebral

prechordal

bones

cal,#{176}genetic,10

responses,
and

and

Differential

spasticity,
and

facial

gens,12’

second
brain
ab-

the
theme

mesoderm

mesoderm

Anlage.
had mini-

infant

whereas

by

ectoderm

the

cleft

a chromoat this

extracephahic

with
holoprosencephaly
the induction
of the

by

median
of

of

is the

emphasized
by
The
association

Prechordal

hypotelorism,

philtrum-premaxilla
1 and 5. One

Figures

ma!

facial

parallel
infants

See

be

ral

Features

of maltrisomy,

anomalies
of

unity

which

review.

COMMENT
Clinical

the set
13-15

irrespective

striking

plained

of

The

13-15

or karyotype.

The

stomach.

Comparison

group.

shown

facio-cerebral

an

karyo-

unable
to complete
The point
underscored

anomalies,

gm). The large
intestine
was incompletely
the cecum
an!
appendix
being
located
in the
middle
of the abdomen,
beneath
the

high

blood

Pathogenesis

were
absent
in
The urinary
bladder
The
two adrenals

ureter.
walled.

2 had
with

the

anomalies

and
shown

this

Patient
associated

unit,

second
anoma-

chromosome

generally

is that

a lawful

46

have

but we were
some
study.

neurons

part of the
and
thin
2.6

the point

urinary

narrowed

formations

13.5 gm. The
right
of hydronephrosis

degree

of skin
generally

1 exemplifies

group
5H

The
defect,

studies

Patient

or per-

the

of

have

bobPamalfor-

extracephahic

normal

second

trivial,

patients

group

apparently

The
cerebral
falx was
only
at the junction
of the tentoriuni
occiput,
and was only 0.5 cm

have

the
groups.5

extracephalic

multiple

Chromosome
the

in

that
two

group
major

whereas

have

wide.

lip

one

mation,

fila-

illustrating
fall into
first

only

group

crista

nerve

BRAIN

at

had

facies

studying

14 such

necropsy,

we

ception

to

median

facial

the

than 75 patients

more

who

rule
anomalies,

Downloaded from by guest on September 23, 2016

patients

found

that

I-IV
not

these
when

and

in
per-

clinically
a single

patterns
present,

ex-

of
pre-

ARTICLES
diet

the

o)ver,

holoprosencephali

virtually

c brain

every

bar
holoprosencephalv.1
1)ilboried,
l)ut
challenging,
is

U)fliOfllC

facies

I-IV,

which

pro)sence)haly,
For

facies

we

V,

patients

refined
in

point

the

of

or

given

illustrate

the

tecting
normal

end

spectrtmni,
reviewed
these

four

the

the

286,

data

tients),

408.

proaches

finds

so

from

does

the

condition

for

diagnosis,

hypotelorism,

cut

condition.

other

de-

clinical
dethe

tions

of orbital

dian

facial

causes

the

the

plastic.
from

face

ap-

patients,

The

in some
diagnostic

hut
cases.

hemispheres

liolopros-

raphy.

The

thus

become

types

I-V,

are

collected,

encephalv
possible,
to

type

after

establish

patients

othersi7

as

such
as
However,
may

more
new

)lacing

seems

B).

It

hold

to

may

patients

catego)ries
such
as 286
catego)rv
VI,

408 and
others
th e face-brain

weaken

(lobar

at

as

in the Table,
of Smith
amid
and

category

correlation

,

strongly
in categories
this level;
Patau’s

VII.
which

I-V.
original

paroxysmal
flattening

illtmmination.’
cian

still

the

patient

patients

grams

will

l)etween
have

to

await

category

V amid normality

cephalometric

and

other

outlines

eral

and

electroencephalog-

study,

abnormal

multiple

in

independent

hypersynchrony,
the

and

areas

of

studies,

doubt

about

is in some

trans-

semilobar
is

suspected.

he

anticipated

previous
or l)rain

authors,

if the

the

way
should
or

atypical,
be done,
bobar
in

are

either

chini-

diagnosis

The

lioboprosencephaly

Some

trans-

cytogenetic

foregoing

has

to

lobar

include

skull,

over

when

I)atient
with
cleft
lip amid ialite
had
olfactory
l)ull)S
audi tracts,’
while
I)1tiemlt
408 who dliii not have
clefts had no olfactory
bulbs
amid tracts.
Any final classification
of

two

roentgenograms,

should

mo)encephabography
ticularly

in our

24

the

After

and
the
or hypo-

be necessary

may

showing

hy-

determined

is invariably

usually

encephaly

the

be

skull

me-

from other
to estab-

is absent
is absent

could

Besides

spikes,

alThe

22

other

differentiate

planigrams

EEG

21,

combina-

with

roentgenograms

of the

po-

in

on

it is essential

dermatoglyphics,2(

patients

based

To

procedures

illumination

408

be

points

skull

frontal
poles
of Patient
163 (lohar
hoboprosencephaly
type
A2) to the completely
cleft
of Patient

20.

hypotelorism

These

cleft

a normal

development,

the crista
galli
nasal
septum

plain

may

hoboprosencephaly

must

defects.

the

patient

of holoprosencephaly

lish that
subjacent

pa-

brain.

of

din-

occurs

defective.i,

of microcrania,

three

incompletely

be

diagnosis

I-V

have

and

will

the

a suffici-

backing

the

and

survival

categories

arrange

the

defects,

normal

many

roentneces-

hypotelorism
in a patient

facial

mentally

of
is not

When

median

is orbital
hypodefined
by Cur-

substantiation

trigonocephaly

can

comparing

as

sary

with

listed
in
clinical

the

on P-A skull
an absolutely

ical

though

Patient

I-IV

rarino
and
Silverman
genograms.2#{176} Although

1)telrismii

only

that

normality,

progresses

On

correla-

anomalies
one for

of categories
as quantitatively

Iatiemits

follows,

for

diagnosis
telorism,

for

o)f increasing

as

(available

one

brain

order

the median
facial
I, the necessary

four

One

ic

Of
Table

temitial

ho)boprosencephalic

facies

and

of
toward

to the

in

I)atients

of

288,

brain

possibility

oriented

face-brain

Procedures

and

however,

facies

one can turn
lv’ Smith.15

normality
163,

of

bulbs

incompletely

exciting

Diagnostic

be

interorbital

classified;

diagnostic

new

the
specific

no

the

is

he

in

because

olfactory

brain

holo-

from

trisomy,
about

cannot

lobar

reported

and

the

and

examples

precluded

13-15

palate,

tracts,

few

several
infants
Unfortunately,

.

are

of

is

distance,

for

type.

and

patients,

of view

statement

to

facies

is obvious

similar

scribed

too

studies

of

tio)mis.

hobo-

abobar

have

correlations

many

clarification

predict

of

brains

literature

clinicopathobogic

toward

formulation
of face-brain
the resemblance
of our

to

prosencephalic

the

refined

alo-

If the much
word
patliog-

6

reliably

a strong
but

relationships,

,

Mo)re-

had

it is justified

usually

to permit
two

2.

justified,

ever

.

has

patient

261

or
pneupar-

holopros-

ventricular
semilobar

shown

in

or
by

sev-

roentgeno-

photographs.1’2531

diagnostic

Downloaded from by guest on September 23, 2016

confusion

may

arise

in

262

FACE

an occasional
holoprosencephalic
who
has
increased
intracranial

pressure.

These

patients

may

an otherwise
observed
one
and

type,2

one

506).l I In
prosencephaly

both,

is

and

Patients
ally

he

\Ve

pictured

by

or

tient

lesser

with

II\T

of

the

potential
first

bobar

year

of

(p.

often
tenth

some

minimum

showed

of environmental

and

awareness,

studies

patients

or brain
malformations
have
a normal
po)tential.2

with

Some
as

the

are

face

predicts

in the
and

this

with

and

bilateral

and
palate
premaxibla
tients

with
Anbage

had

cephaly),

an

arrest
or

and
an

brain

in

1. Yakovlev,

2.

of

proplasia

bulbs.

intermediate

stage

facio-cerebral
with
cycbopia,

brain

transform

through

diagnostic

of

Careful
will

relationships

fects
zures,

normality,

oif

cebocephaly,

can

include
rigidity,

development.

me-

the type
attention

of brain
malto face-brain

significantly

extend

facies
which
Physiological

poikilothermia,
and
lack

of

the

palate

Alohar

: Clinical,

considerations.
196:3.

Cacciatore,

the

philtrum.

A. :

Decker,

the

facial

(Basel),

trisomv

man.

karot’pe
on

the

(Smmhmitted

for
der

Anatomic
Springer,

of

(arhin-

pubhicatiomi).

speziehlen

unc!

in

relation

hoboprosencephialy

B. : Ilandbhuch

1)ulthiol-

Ilistologie,

13/4

1956.

F. :

Congenital

miialforniatiomi

J.

Neuropath.

Exp.

brain.

prc-

of

1960.

remarks

to

and

devebopmiient
40:278,

with

prenuttuul

maxihla

\V. : A 46 chromosonie

olettler,

de-

lcconstr.

D. : The

j.

of

Amiat.

Berlin:

The

Plast.

1962.

the

gischen

bobmediami

electro)ence1)h-

nosologic

and!

in

l)eMer,

of

Exp.

with

and

30:313,

B. S.,

ence1)haly).

7.

Neumropath.

\V. :

23 :1,

W.,
of

13-15

of

Neurol.,

the
6:98,

1947.
Kuhlenbeck,

Ii. :

Confin.
9. Ad!elmanml,
Quart.

10.

\Vright,
the

pg

guimiea

alobar

ce1ihalv)

ovitli

Re1)Ort

\V.,

Thacker,

hiummiian

di(ncephabomi.

\V.,

median

Comp.
and!

Phosiol.,

C. C.

Palmer,

Downloaded from by guest on September 23, 2016

(arhiinenlii)

46

aml

1)uuhtt(.

chiromosonies.

1963.
L.

J. :

dept
ooith

13:913,
James,

E.

Cell.

holoprosemicephaly

patient

of

Neurolog,
Binns,

j.

1960.
\V., Zeman,

Familial

12.

The

Neurol.,
Sumppl. 14, 1954.
H. B. : The
1)rohlem
of cvcbopia.
Rev. Biol.,
11: 161; 284,
1936.
S. : The gemietics
of vital characters
of

56:123,
1 1. I)eMyer,

curde-

apnea,
seipsychomotor

Zeman,

an(l

cebocephalo,

8.

two
patients
preo)f these
patients

diagnostic
be recognized.

and

an!

I.

Acta

of

extends

J.

Neurol.,

Monie,

stuld!ies

Arrhinenceph-

(arhinencephal)

lip

niaxilia

are

series

or

1959.

\V.,

6. Ostertag,

malformations
which
and then,
as face and

cleft
lip, and
the
here.
The
facies

formation.

number
rently

a graded

ethmocephaly,

dian
sented

with
poles

in

The
brain

III.

inter-relationships

by

patients

trisoniv.

I. : Pathoarchitectonic

18:22,

I)eMyer,

4. Kraus,

5.

frontal

two

46

anomalies

(holotelencephahies).

Surg.,

cleavage

The

13-15

malformations.

cleft

philtrumBoth
pa-

of

toward

l.

abographic

lip

characterized

no

a

hoboprosencephalic

prosencephaly

series

of

or

have

extracephalic

O)f

Neurol.,

(arhinen-

prosencephalic

olfactory

are

hypoplastic
are described.

defect

incomplete

median
begins

cleft

have

to
the

uilies

hypotelorism,

holoprosencephaly
a

no

a

apt

velopment

lateral

such

few

karvotype.
Others,
such as Pamany
extracephalic
anomalies.
suggests
that
the batter
pa-

Confin.

orbital

ts,

have

REFERENCES

SUMMARY
j)atients

who

malformations,

irrespective

these

degrees

patien

I)atiemit,

cerebral

to be cared
other
hand,
in

pmieumoencephalog-

karvotpe.

evidence

mildest

chromo)some

sometimes

first

tients

even

electroencephal-

hoboprosencephalic

our

The

pa-

galli,

skull

hvpotelor-

raphy.

3.

nose,

and

,

usti-

fare

hut

face

Two

crista

include
orbital

dermatoglyphics,

life.

dying
patient1

the best of the lot, had
young
infants.
On the

the

flat

absent

chromosome
tient 2, have
The
literature

Table

malformations

studies
to show

ography,

and

hoboprosencephalic
facial

slightly
better,
although
first
year.
Yakovlev’s
othersl

diagnostic

extracephalic

the

semilobar

may

Potter

the alohar
bobpredicted
from
the

ficies

within

patients,
for like

have
of this

infant

developmental

die

ism

microcephalic,

Management

with

no

Useful
roentgenograms

facies.

Prognosis

BRAIN

patient

finding.

however,
could
be

pathogmiomonic

have

not

constant
hvdrocephalic

AND

F.,

Shiupe,

Cvcbopian-tpe

J. L.,

an(l
miialforma-

ARTICLES
tions

in lambs.

Arch.

Environ.

health,

5:106,

263
23.

13.

Ingahis,

T.

II.,

and

(ctromelia,
fish.
14.

an(l

Arch.

Potter,

2nd

Sniithi,
L.

\V.,

D.

trisomv

10:389,

Pe!iat.

Inhomn,
trisomv

aiio!

D.

D1

congenital

an

E.

H.,

autosome.

and!

28.

Gerald,

brain

P.

defect

trisomv.

.

5. :

specific

A

K.,

(arhinencephaly)

Emigl. J. Med.,

New

Therman,

E.,

Patau,

R.

I. : The

l)eMars,

xO

J.
20.

gonadal
Humii.

Currarino,

G.,

265:

Bertelsen,

T. :

the
cranial
Suppl.,
51:1,

and!

F.

J.

two

74 :206,

M.,

Acta

H.,

Kausuistischer

and

deWulf:
(les

Rev.

Identity

and
19:72:3,

surgical
1962.

30.

Kbh.,

31.

con-

Paediat.

die

deux

cer#{233}brales,”
et

sur
I.

et

median).

1947.
bes

dysraphies

Ag#{233}n#{233}sie
des

La

lobes

Neurol.

Morsier,

C.

1955.
de: La

dvsplasie

Trois

cas

observes

chez

et des
(teben-

dysplasie

Arch.

he

Neuropath.

Gauthier,

G. :

Acta

Neuroveg.

La

Downloaded from by guest on September 23, 2016

dsplasie

(Wien),

des

riuelle

cliniques

79:591,

Etudles

cas

exceptionnelle:

olfactoPsychiat.,

o)lfacto-g#{233}nitale.
veau.
Essai
do
Ben.,
1:433,

1962.

J. C.:
treat-

fissures

Neurol.,

de:

t#{233}ratogen#{233}se.
Acta
Todt,

zum
dIes

ilelv.

Etude

anatomiiiques

C.

umnd

cer#{233}brale

g#{233}nitahe. Schweiz.

of

Beitrag

Cyck’ncepsahie
lateral
ventricle.

synraphie

Morsier,

Neuro-

1954.

1952.

cephaloschizis

Orbital
trigono-

syiiostosis

13: 117,

(lysgenesie

74:309,

Ophthal.,

J. L., and

Gwinn,

Neurosurg.,

7:98,

J.

structures.

Neurol.,

olfactifs
(t#{233}lenc#{233}phaboschizislateral)
conimiiissures
cahleuse
et anterieure

1960.

prematumre

B., and Maloney,
J. : Malformaforebrain
with comments
on the
dorsal
cyst, the Corpus
callosum

der
single

Gastaut,

Epi!ep-

midl

1940.

cranio-encephialiques.

Amer.

F. :
and!

holoprosencephaly

preparation.)

13:97,

H. :

entraine.

29.

and

sisters.

Silverman,

The

and

in

(In

hiippocanipal

Exp.

anomalies

120,

\V.,

syndrome

the

Zlloveger,

“La

1961.

sumtures.
1958.

Trigonocephaly.
ment.

in

13:193,

Radiology,

Anderson,

D trisomily

D.

arhinencephalv

cephalv.

22.

Smith,

dsgenesis
C.enet.,

hipoteborism,
21.

K.,

the

of

dlune

in

1963.

19.

Lichtenstein,

Acta,

Alkami,

P. : Electroencephalo-

A. : Gehirnmissildung

l)roblem
genital

congeni-

extra

C. : Evaluation

medical
genetics.
10:409,
1963.

Amer.,
Whiite,

Nervenarzt,

and!

Inhorn,

H.

in

and!

Bannwarth,

1)ath.

1960.
Picard,

S.,

Warner,

E.,

Soltan,

abnormalities

tion

Amer.,

P. : Multiple

by

W.

so-called
and

N.

Thermami,

H.

caused

J. Q.,

13-15

\V.,

Wagner,

1:790,

Lancet,

26.

27.

Smiiith,

anomaly

Miller,

Chin.

and

(arhinencephal).
25.

1963.

K.,

S. L.,

18.

In-

Medical

K., Thermiian,
E.,
R. I. : The
D
62:326,
196:3.
No. 18 trisomy

syndiromes.

Patau,
tuil

Patau,
I)e\Iars,

A.,

graphic

the

Book

I.

l)eMyer,

sic.

J. Ped!iat.,
\V. : The

svmidrome.

17.

1962.

amid

Year

24.

1961.

and!

Smith,

Fetus

Chicago:

Zebra

in

5: 1 14,

tild

of

Ed.,

I).

S.
16.

health,

E. : Pathology

fant.

U. : Cycbopia,

miionstrosities

Enviromi.

Pumblishers,

15.

\Itmrakaiiii,
other

Uchida,

of dermatoglphics
Pediat.
Clin. N.

1962.

olfacto-gemiitale.

21 :345,

1960.

THE FACE PREDICTS THE BRAIN: DIAGNOSTIC SIGNIFICANCE OF MEDIAN
FACIAL ANOMALIES FOR HOLOPROSENCEPHALY (ARHINENCEPHALY)
William DeMyer, Wolfgang Zeman and Catherine Gardella Palmer
Pediatrics 1964;34;256
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication, it
has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked by the
American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village, Illinois, 60007.
Copyright © 1964 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005.
Online ISSN: 1098-4275.

Downloaded from by guest on September 23, 2016

THE FACE PREDICTS THE BRAIN: DIAGNOSTIC SIGNIFICANCE OF MEDIAN
FACIAL ANOMALIES FOR HOLOPROSENCEPHALY (ARHINENCEPHALY)
William DeMyer, Wolfgang Zeman and Catherine Gardella Palmer
Pediatrics 1964;34;256

The online version of this article, along with updated information and services, is located on
the World Wide Web at:
/content/34/2/256

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly publication,
it has been published continuously since 1948. PEDIATRICS is owned, published, and trademarked
by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove Village,
Illinois, 60007. Copyright © 1964 by the American Academy of Pediatrics. All rights reserved. Print
ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from by guest on September 23, 2016