HEREDITARY

L.

SOLOMON,

Fro,n

the

The

earliest

the

reference

detailed

century

all the
has

case

been

reports

described

Nevertheless,
associated

the

have

evolution

of these

growth
1,124 cases

of

in 1925 was marred

by inaccuracies
in the absence
of sufficient
evidence
entrenched

The
in a study

in the

clinical,
of this

Sick Children,
paper
(Solomon
cartilage-capped

disease

exostosis

was

Reports
had

since, and
1943).
curious
lesions,

are still
collected

been

their

described

(Bessel-Hagen

earlier
their

Royal

and

genetic

National

MATERIAL

distribution

papers
upon
conclusions

and

AND

have

Hospital

been

and

re-examined

the

Hospital

for

described
in a previous
and distribution
of the
lesions.

METHODS

at the Hospital
for Sick Children
for study
if indexed
under
any

and the Royal

of the following

exostosis,

aclasis,

National
headings

multiple

exostosis,

Orthopaedic
: hereditary

exostosis,

diaphysial

osteochondroma,

ecchondroma,

enchondroma,
chondroma,
chondromatosis,
chondroplasia,
Olliers
disease,
chondrosarcoma.
In most
instances
an examination
of the
notes
to

and

the

available

separate

those

(diaphysial
cases

radiographs
with

aclasis)

were

not

true

from

Thirteen

further
nine
but completed

patients

patients

could

declined
to attend
questionnaires.

The remaining
fifty-six
nucleus
of this study.
Four

of a sessle
exostosis.
End-on
gives the appearance
of vacuolation.

could

morbid

anatomical

292

be

traced
and

from

their

histological

earliest
examinations

one

as a result

were

examined

of this
in

logically.
In
were
available

each
for

appearance

the

of the

to

lesions
THE

case

exostosis
Doubtful
had
been
were

found.

not

be traced;

for

examination

patients
of them

disease;

dys-

sufficient

multiple

others.
until
they

included

of these

was

the

examined
by the author.
Records
of seventy-eight

lesions

the

which
they drew.
Yet
have gradually
become

characteristics

Orthopaedic

multiple

Radiograph
projection

of

and largely
unexplained.
by Stocks
and Barrington

Great
Ormond
Street.
The abnormalities
ofgrowth
were
1961).
The present
paper
deals with the development
exostoses
and the complications
associated
with these

All available
records
Hospital
were collected

turn

of the cartilage-capped

unusual

defined
literature

in 1814.

By the

the pathology

incompletely
from
the

by Boyer

in 1825.

disease.

pathological
at the

disease

in most of the
to the contrary

of the

description

radiological,

of the

the

London

multiple
Hospital

appeared
(Jaffe

and

Street,

Guys

features

AFRICA

Hospital

Ormond

hereditary

in the

of

analysis

Great

in detail

abnormalities

A statistical

Orthopaedic

Children,

with

clinical

SOUTH

National

appeared

important

1 89 1). Innumerable
exostoses

Sick

to a family

description

EXOSTOSIS

JOHANNESBURG,

Royal

Hospitalfor

A more

MULTIPLE

the

formed
have

other

the
died,

fifty-two

detail,
clinically
and
radioinstance
earlier
radiographs
comparison
and
often
the
present
were

JOURNAL

time.
also
OF

BONE

When

carried
AND

possible

out.
JOINT

SURGERY

HEREDITARY

another

In addition
to the patients
forty
forty-four
were
examined

subjects,

in whom

on

growth

bone

Differentiation

literature

anthropometric

of

were

family

and

led

multiple
Indeed,
to

exostoses

or cross-inheritance
Although
there
and

relatives
clinically
data

in diaphysial
aclasis
from dyschondroplasia

case descriptions
enchondromatosis.

MULTIPLE

were

exostosis
Stocks
and

conclude

that

in others,

and

between
them
are superficial

were
but

disease;

enchondromata

any

kind

as a radiolucent
extending
longitudinally

may

seems to be possible.
similarities,
particularly

streaking
from

of a previous

study

basis

two

occur

in

of the

two

in the
separate

history;

some

members

disorders

with

never.

are small
and
radiological
pattern,

forearms

conditions

in dyschondroplasia

due
the

of

in families

of the

distinct

of the metaphysial
region,
the epiphysial
plate
into

older

or multiple
review
of the

deformities
and

the

of

of dyschondroplasia
in their exhaustive

of admixture

spurs
or exostoses
that do occur
in dyschondroplasia
are the least significant
feature
of a well recognised

characteristically
of cartilage

the

and
these

enchondromatosis)-Most

include
examples
Barrington
(1925)

it is now well known

that these
are
clinical,
radiological
and genetic
features.
multiple
exostosis
there
is usually
a family

In
bony
they

formed

and radiologically
Seventy-six
of

1961).

ankles,

different

examined
clinically
not radiologically.

obtained,

(Solomon
(Oiliers

293

EXOSTOSIS

The

few in number;
which
appears

to retained
diaphysis.

columns
Central

enchondromata
are also common,
particularly
in the metacarpal
bones
Figure
1 shows
what has often
been mistaken
for an enchondroma
exostosis.
This appearance
is due to the radiographic
projection
giving

and phalanges.
in a case of multiple
an end-on
view of a

large

in hereditary

sessile

exostosis.

Central,

expanding

chondromata

do

not

by

some

occur

multiple

exostosis.
CLINICAL

The

name

simplicity,
the term
heritable

hereditary

cartilage-capped

exostoses

is completed
mities
resulting
bones

multiple

avoiding
any reference
diaphysial
aclasis-conveys
disorder
of the skeletal
which

PRESENTATION

exostosis-preferred

people

for

appear

by certain
characteristic
from
deficient
growth

in

different

deforof the

descriptive

parts

of

the

skeleton.

The

picture

70

involved.

Over 80 per cent of the patients

are
covered
in the first decade
of life males

disand

affected
with equal
frequency
(Fig. 2). The skeletal
distribution
is shown
in
Figure
3. In fact the earliest
lesions
may be
present
at birth
and are occasionally
detected
females

60
50

being

soon after by the searching

hands
of a parent
herself
afflicted
by the disease.
The
mere
presence
of a bony
lump,
coupled
with the
knowledge
is sufficient

that the disease

is
reason
for seeking

in the

majority

vast

in the family,
medical
advice

MALES:

49.

FEMALES:

50.5%

30
20

of cases.

____

FIG.2

Age and sex distribution

of multiple
exostosis
in fiftytwo index patients
and twenty-four
relatives
examined
radiologically.
The histogram
shows the age at which
lesions

were

first

discovered.

10
AG

IN
FIG.

45 B,

NO.

2,

MAY

1963

5%

10

VOL.

its

to the basic
pathology,
as yet unknown,
but hinted
at in
at least two important
features
of the disease.
It is a
system;
and its most striking
manifestation
are the numerous

15
YEARS
2

i
20

25

294

L. SOLOMON

mutants,

New

discovered
some other

24

deformities
first
42

on

the

other

accidentally
in the
illness.
Occasionally
or

calls

the

effect

attention

to

of

the

hand,

pressure

by

disease.

unaware

of the other
and
visible

of the lesions
is common
throughout
The patient
in an established
teristic
be seen

appearance
and palpated

more

actively

skeleton.

at the
of the

borders

Bone
deformities

of the

bilateral
absence

pectoral

bones
as well.
as the picture

after

the

natural

cessation

others
The

adjacent

how

seldom

structures.

In

large

pelvic

exostosis

renal

failure

and

uterus

occurred

and
were

they

case

urinary

malposition

in another.

arterial
aneurysms
not encountered

interstitial
pressure

one

death;

of

the

or

disease

Intestinal

have
in the

and
functional

exostoses

interfere

caused

it is

seriously
of

with

this

series

obstruction,
of a pregnant
obstruction

been
described,
present
series.

but
An

or subcutaneous
on a peripheral

bursa over an exostosis,

nerve or interference
with

tendons,

though

hardly

ever

removal
exostosis

of the
occurred

exostosis.
in two

removal

of the

loose

characteristic

lesions

serious,

may

call

for

Fracture
of a stalked
patients
and necessitated

fragments.
FIG.

The

growing
ends

scapulae,
too,

parts
in

of the

this period.
presents

of

the

origin,

tubular

the iliac
is affected,

in approximately

is unremarkable

there
is little
disturbance
of health
activity
in the usual
case.
Despite
the large
number
of
surprising

case

years of
or other
a charac-

three

endochondral

they

bones,

crests
giving

occur
in haphazard
association,
unmistakable
radiological
features

course

of growth

During
the
pain in one

Soon
of a

are

the

found

vertebral

and ribs.
rise to recognisable

out

of every

four

of

formity
of the knee and ankle,
tibio-fibular
synostosis
and
pelvic
girdles.
Of these,
only the ankle
deformity
is usually

and

and symmetrical;
the
of associated
exostoses.

Complications-The

their

these
subjects
(Table
I).
The commonest
are a shortness
of stature,
bowing
of the radius
with ulnar deviation
of the
wrist,
subluxation
of the humero-radial
joint,
valgus
de-

Distribution
of the exostoses
in fiftytwo index patients
and twenty-four
affected
relatives.
Numbers
are expressed
as percentages.

asymmetry

growth,

of

(Fig. 4). Numerous

bony
lumps
may
as they jut into the soft tissues
around

Juxta-epiphysial

typically

some

of the tibia and scapula

are usually
discovered
because
they are the most conspicuous
sites
A radiograph
at this stage invariably
shows
in many
palpable

remain

that

too,

Lesions
first, simply
in the child.

the

FIG.

exostosis

so mildly
throughout

exostoses
become

as to
life.

an

Doubtless,

generalised
skeletal
disorder
unfolds.
rapid growth
the exostoses
enlarge
and

Qi

sometimes

are affected
abnormality

early
these

Q4

are

course
of investigations
for
it is one of the secondary

in hereditary

multiple

exostosis.

but none ever in the

are described
below.

HEREDITARY

The
exostoses,
in

this

after

MULTIPLE

295

EXOSTOSIS

most serious
complication
is malignant
which
occurs
in a significant
percentage
series

developed

a hindquarter
The

carcinoma

a chondrosarcoma,

amputation.

other

three

of the

change
in one or other
of the cartilage-capped
of cases.
None of the fifty-six
index patients
but one of the secondary
cases
did so and died
is discussed
in detail
below.

deaths

lung,

This

subject

not

attributable

were

another

died

to this

of cardiac

failure

TABLE
INCIDENCE

(Fifty-two

index

Se
x

and

the

: one
third

had

a primary

DEFORMITIES

twenty-four

Multiple

Associated

exostoses

deformities

affected

relatives)

Percentage

with

deformities

Male

36

26

72

Female

40

30

75

76

56

73#{149}7

Total

patient

of bronchopneumonia.

OF

patients

disease

and

HEREDITY

Most

of our

knowledge

about

the hereditary

from
Stocks
and Barringtons
(1925)
cases they concluded
that the disease
an affected
parent;
that in one-quarter
she remained
unaffected
herself;
that
from

generation

to generation

; and

Unfortunately

many

of the

dyschondroplasia.
of the disease

by an

Furthermore,
unaffected

radiological

examination.
of the index

Forty-six

disease,

that

sources

patients

which

the

upon

of the
mother

of the

is being

females
appears

was 24 : 22. Sixty-three

per
to be determined
by a single

sex

ratio

which
thirteen
to her

in this

pattern

characteristics

of multiple

exostosis

is derived

report.
From
a statistical
analysis
of 1,124 recorded
was inherited
in 64 per cent of the cases,
usually
from
ofthe
cases in which the mother
transmitted
the disease
the number
of exostoses
in individual
cases
increased
work

quoted
offspring,

present

reported

a 7 : 3 preponderance

showed

this

series

was

based

included

of males.
examples
of

instances
of presumed
transmission
none
was verified
by physical
and
were

in detail

used

in a study

elsewhere.

The

of the hereditary
ratio

cent of these patients

had an affected
parent.
gene which
always
produces
some detectable

of males

to

The disease
bony lesion

in the heterozygote.
No subject,
either
male or female,
was found
to have transmitted
the
disease
without
being affected.
The condition
was inherited
by about
half the children
of affected
parents;
there
was no
tendency
for the lesions
to increase
in successive
generations.
The type and distribution
of the lesions
showed
no tendency
to intrafamilial
resemblance
except
in one family,
where
had exostoses
predominantly
the long bones
being
only

six of the affected

members
on the bones
of the hands,
mildly
affected.
It is possible

(two sisters
each with two children)
the more
usual
sites at the ends of
that a different
gene is concerned
in

this

only

to be responsible.

family.

In the

others

EVOLUTION

The
(though
irregular

one

OF

characteristic

lesion

this is often
in outline,

seen as well)
heaped
and

45 B,

NO.

2,

MAY

1963

THE

in multiple

One or more
of these may enlarge
outline,
sometimes
cauliflower-like
VOL.

mutant

gene

appears

LESIONS

exostosis

but rather
a diffuse,
cleft by innumerable
and
and

IN

MULTIPLE

is not

the

EXOSTOSIS

pedunculated

club-shaped
thickening
bony excrescences

project
as a pedunculated
of frightening
dimension.

mass,

cortical

exostosis

of the metaphysis,
or sessile exostoses.
sometimes

smooth

in

L. SOLOMON

296
.--

-1

The
growth

initial
is not

and

may

of the

deviation
related

occur

growth

Thus

normal

from

to any

at any

time

period

for

growth

normal

factor

birth

from

that

may

bone

precipitating

to the end

particular

precede

bone.

and

follow

starkly
abnormal
interlude;
or new exostoses
may be discovered
at successive
visits.
However,
in the present
series there
was no instance
of a
new
-

exostosis

The

an

S.

arising

earliest

after

asymmetrical

cortex

the cessation

lesion
or

immediately

beaked

epiphysial

projection

growth,

to

Exostoses

of the phalanges
in various
development,

stages

model
irregularly

duces

the

result

is totally

club-shaped

characteristic

at all.

The

occurs,

varying

patient

and

unpredictable,

abnormality
not

even

FIG.

nor

appearance
is it certain

manifests
only

within

from

the

same

itself

patient
bone

shaft

patient

at different

heaped

FIG.

but

6-A

growth.
Figure

Figure
8-Different

into

be followed
exostosis

times

by normal
jutting

from

to

will
an exostosis

each

another

FIG.

THE

pro-

of these

time

in the

same

8).

of the radius,
the development
of which
7-Broadening
and deformity
of the humerus
types of lesion affecting
the femur at different
apparently
normal
growth.

metaphysis,

phenomenon
bone

one

(Fig.

a broad

(Fig. 7). Which

site will develop

isolated
from

small exostosis

Figure

proceeds,
The juxta-

(Fig.

of the bone end

that any potential

as a completely
to

epiphysial

6); or the asymmetrical

in width
may
be established
as the new
for
further
growth,
and
new
bone,

increase

of

may

of the

the

as growth
evolve.

an isolated

leaving

the diaphysial

FIG

radiologically
overgrowth

adjacent

plate (Fig. 5). Thereafter,

one of two patterns
may

of growth.

detectable

was followed
by ten years of normal
arising
during
the same
period.
times, with intervening
periods
of

JOURNAL

OF

BONE

AND

JOINT

SURGERY

it

HEREDITARY

Associated
gives

rise

causes

ofthe

radius

Excessive

The

other

diaphysial

thickening

of secondary

a number

bowing

joint.

the

with

to

and

ulnar

deformities

there

fibula

ofthe

causes

coxa valga and shortness

of the
development
of these abnorhas
been
described
in detail

defect.
malities

(Solomon

1961)

and

will not

wrist

of bone

deformities

of stature,

hands

and

of the

are

which

of the

ofthe

asymmetry

feet

growth

shortening

or subluxation

valgus

as shortness

girdle,
The

pelvic

is a retardation
Disproportionate

deviation

such

297

EXOSTOSIS

deformities.

of the

shortening

common

MULTIPLE

ulna

radio-humeral

ankle

and

of the

all accounted

knee.

pectoral

for by the

or
same

be discussed

here.

As

long

ago

that

suggested

tudinal

growth

irregular
riot

1891

known

what

part

bone

of

loses
it

growth.

longi-

there

is

these

phenois that both

abnormality

and the exostoses

the ordinary
sense

in

exact

two

is important

growth,

an

in
still

between
a generalised

neoplastic

in

squanders
It is

whether

What

mena.

Bessel-Hagen

bone

transverse

relationship
are

as

the

of
are
of

not
the

word.

In

each
exostosis
ofthe
bone

structure
an

cortex

outer

cavity

continuous

bone.

Thus

the

cap

in
of

which

Here

the
crudely

and

Sometimes,
was

Lorincz
greatly

connective

by the
between
normal

than

outer

the

radiograph

part

of the

mass

covering

the bony

proceeds
the epiphyses

the cap

or

projection.

slowly
and
join (Fig. 9).

is thinned

to a narrow

After
lining

however,

it persists

and

may

(1960)
increased

found
that
in multiple

the

urinary
exostosis

even

the cessation
which

ofgrowth

may

increase

most

be entirely

absent

(1962)).

In

the

four

adults

a metabolic
Degeneration

abnormality.
and calcification

appearance

which

45 B,

NO.

2,

often
MAY

1963

the

AMPS

of the
causes

bulk
there

was

not

of cartilage
is no need

cartilaginous

unnecessary

cartilage
places.

excretion
of acid mucopolysaccharides
(AMPS)
and suggested
that this was due to a disorder
of

excretion

by the increased
exostosis,
and

ofthe
in many

in size.

tissue
AMPS
metabolism.
This investigation
has been repeated
in
more
accurate
method
of Di Ferrante
and Rich (1956).
The values
in
the ages of five and sixteen
were all considerably
above
the mean but
range (the normal
standards
used were those of Teller,
Burke,
Rosevear

equally
well be explained
in children
with multiple

VOL.

in con-

columnar
arrangement
of the
cells
of the
epiphysial
plate
reproduced,
and
endochon-

dral
ossification
irregularly
until
ossifies

of the

not sit upon

but arises
bone.

cartilaginous

surmounts

cartilage
is

size

marrow

cavity

does

parent
the

suggest,

inner

the

cortex,

the

Larger
consists

an

the exostosis

with

would

and
with

underlying

tinuity

is reproduced
the
from which it arises,

mass
alarm

raised
(which
on the

produces

(Fig.

10).

at all.

These

eleven
seven

still
and

patients
children
within
the
McKenzie

findings

may

is the main source

of AMPS)
present
evidence
to postulate
a characteristic
The

patchy

radiological
density

on

the

298

L. SOLOMON

FIG.

10

Radiograph
showing
dense calcification
of a cartilage-capped
exostosis
of the scapula.
The
uniform
density of the tumour
with its clear margins
and the normal
bone texture elsewhere
suggest that this is a benign lesion.

FIG.
Cross-section

of

tissue

the

have

calcified

exostosis

shown

replaced

the degenerating

II
in

Figure

cartilage

10. Confluent
throughout

THE

JOURNAL

masses

of calcified

the tumour.

OF

BONE

AND

JOINT

SURGERY

HEREDITARY

radiograph

may

change.

indicate

However,

pattern,

and

point
chalky

a tumour

unlike

the

limits

MULTIPLE

of enormous

size,

a chondrosarcoma,

of the

calcified

on the radiograph.
Extensive
material,
and calcium
detritus

areas
may

can

dividing
is hard

suggests

the

(Bennett

and

line between
to determine.

possibility

of

Berkheimer

possibility

shows

and

of malignant

a uniformity

unequivocally

in the

traced

at every

of degenerative
cartilage
are replaced
by the
occur also in the bony part of the tumour
(Fig.

abnormal
Any increase

malignant
1941) and

the

exostosis

be clearly

MALIGNANT

The
exostosis

suggesting

a benign

area

299

EXOSTOSIS

soft,
11).

CHANGE

growth
and neoplasia
in size after the normal

change;
here the

in a cartilage-capped

period

but children,
too,
point
of departure

of growth

suffer
from

always

this complication
benign
growth

is

imperceptible.

.,

.:.:,
#{149}.

I,

..*

..,

t.,:

I.

V.

,bi

#{149}1

...

#{149}

..

#{149}

..c
A

j.l
14

.#{149}

.,A

I
#{149}#{149} /

#{149}

.1:

.*

-S.,
#{149}?

*,,

.4

.:

4,?
4

*4

I
*

#{149} i,

.,s,,

#{149}

FIG.
12
FIG.
13
12-Radiograph
showing
a chondrosarcoma
developing
in a cartilage-capped
exostosis.
The variegated
the poorly defined outline
of the tumour
and the signs of bone destruction
strongly
suggest malignancy.
13-Photomicrograph
showing
the features
of a chondrosarcoma.
Note the marked
cellularity
and the
pleomorphism
of the tissue.

Figure
density,
Figure

Dahlin

(1957),

on

the

basis

of 272

cases

of osteochondroma

of

all types

studied

at the

Mayo
Clinic,
estimated
the incidence
of chondrosarcoma
in patients
with multiple
exostosis
at more than
10 per cent.
Jaffe (1958)
believed
it to be about
25 per cent.
These
figures
are
much
higher
than the experience
of most clinicians
suggests.
None
of the fifty-six
index
patients
in the present
series
developed
this complication.
Among
the secondary
cases only one example
of a histologically
proven
chondrosarcoma
was
discovered.

The

patient,

who

had

been

aware

of multiple

bony

remember,
injured
his right thigh at the age of fifteen.
the site of injury
and increased
steadily
in size over the
a radiograph
diagnosis
VOL.

45 B,

showed

a large

of chondrosarcoma
NO.

2,

MAY

1963

cartilaginous
was

made;

tumour
amputation

swellings

for as long

as he could

Six months
later a lump
appeared
at
next two years.
At the age of eighteen

at the

proximal

was

advised

end
but

of the femur.
refused

by the

A clinical
patient.

300

L. SOLOMON

in spite

ofradiation

evidence

of

invasion

of the

treatment.
there

was

bone

therapy

the tumour

destruction

with

tissues

as well

soft

plump
nuclei
for diagnosing

by steady
deterioration
Several
important
are

developed
the

increases

unrelated

condition

Radiation
as the

in size
before

therapy

diagnosis

has

and

the

no effect

and
(Fig.
and
by this

BETWEEN

Femur

Tibia

chondrosarcoma

proves

tumour;

Radius

RATE

Proximal

The

OF

its

it should

to surgical
but
presence

the alteration
commonest
sites
in the literature

Characteristically

the

patient

may

die

of

malevolence.

be removed

completely

as soon

II

GROWTH

figures

lesions

actively
are
These

of

72
62

95
82

Proximal
end
Distal end
.

55
45

69
55

91
72

Proximal
end
Distal end
.

80
20

65
3

85
4

Proximal
end
Distal end
.

25

75

64

85

Proximal end end .

Distal

15
85

527

689

contribution
are after

of the proximal
Lacroix
(1951).

for the proportionate

ends to bone length

exostosis

are

(Fig.
are the

not

OF

strictly

3).
sites

been

13

and

distal

LESIONS

limited

to bones

The tubular
commonly

satisfactorily

representative
distribution
within
of

than

10

bones,

involved;

developed

in cartilage;

the

the iliac crests

and
in the long
bones

the
the

the most heavily

affected
of all (Table
II). On the other
hand
and carpal
bones,
the patellae,
the vertebral
bodies
and the

have

selective

disease

#{176} #{176}
a

60
40

examination

the

e7eniige

Proximal
end
Distal end
.

is characteristic
of the scapulae

this

Number of
cases
affected

peculiarities

that

EXOSTOSES

77
94

growing
ends are
rare in the tarsal

Radiographic

OF

58
71

end

end

FREQUENCY

20
80

in multiple

distribution
borders

AND

cases)

DISTRIBUTION

peculiarity

femur.

indeed

Ul na

shown

ofthe

late;

Distal

Humerus

has

end

occur

Fibula

sternum.

afterwards.
often precedes

is difficult
to prove.
The
of the patients
reported

Proportionate
contribution
to
bone length (expressed
as a
percentage
oftotal elongation)

Bone

exostoses

he agreed

of a chondrosarcoma,
of the tumour,
the

he died soon
case.
Injury

or the proximal

(Seventy-six

more

radiological
suggesting

the increased
mitoses
conformed
to Jaffes
13). Disarticulation
at the hip was followed

metastases

on this

there was
tumour,

of twenty-three

histological
features
marked
cellularity

TABLE

The

age

years later
the calcified

is made.

RELATIONSHIP

detailed
vertebral

to

a causal
relationship
hip:
more
than
half
in the ilium

slowly

Four

outline

At the

the
The

of his general
condition
features
are illustrated

the chondrosarcoma

tumour

some

12).

and double
nuclei,
chondrosarcoma

clinical
pattern,
though
the bones
around
the

in

(Fig.

in size.

hazy

A biopsy
at this stage showed
still no evidence
of metastasis.

of cells with
(1958) criteria

in the

increased
a more

a reflection

at the different
sites.
The distal
end of the humerus
plates
contribute
very little to bone

explained.

sites at successive
the endochondral

of certain

differences

ages in forty-one
skeleton
may
in the

normal

subjects
be less a
process

of

growth

and the proximal

end of the
length,
are no more frequently
THE

JOURNAL

ulna,
where
the epiphysial
affected
than a tarsal
bone
OF

BONE

AND

JOINT

SURGERY

HEREDITARY

such

as the

after

the

main

calcaneum
body

of the

The

other

tarsal

and

Radiographs
two unusually

However,

when

which

also
bone

carpal

of the wrist taken

dense ossification

the

development

develops
has

bones

VOL.

45 B,

NO.

2,

MAY

1963

hardly

301

EXOSTOSIS

an epiphysial

been

ossified

(Fig.

ever

show

plate

and

grows

somewhat

of these

bones

is traced

in length

3).
obvious

lesions

in routine

FIG.
14
at five, nine, ten and twelve years of age. The earliest
centres in the bones which later developed
miniature

growth
can be demonstrated
at some
typical
case is illustrated
in Figure
14.
of

MULTIPLE

by serial

stage in at least half of the

At five years two unusually

radiographs,

radiographs.

film showed
exostoses.

abnormalities

patients
so examined.
A
dense
ossification
centres

302

L. SOLOMON

appeared-one
had developed
in

in the triquetrum
miniature
exostoses

and

size

overtake
radiograph

shape.

and another
in the scaphoid.
and the distal
pole of the

Thereafter,

as

these
bony
irregularities,
taken
at the end of

growth

proceeded,

Four years later these

triquetrum
was clearly

centrifugal

gradually
obscuring
growth
would
probably

ossification

two bones
abnormal

appeared

them
in later radiographs.
show
no sign at all of

to

A single
these
early

abnormalities.
bones

Only the
behave

carpal
bones
have been studied
in this
similarly.
They have this in common,

all directions

from

transport

of

ossification,
bones.
The
bodies,

the

the

centre.

growing

Consequently

end

from

its

there

develop

two

annular

it seems
likely that the
growth
and ossification

is no elongation

original

position

no extensive
modelling
process-all
presence
or absence
of an epiphysial

which

way;
that

relative

characteristic
plate as such

epiphysial

centres

at

of the

bone,

the

primary

to

other
small
proceed
in
no

marked
centre

of

features
of growth
in tubular
is not important.
The vertebral

the

upper

and

lower

surfaces,

are

extremely
rare sites of the disease.
On the basis of these observations
it is suggested
that all the bones
developed
in cartilage
are equally
exposed
to the genetic
disorder
in hereditary
multiple
exostosis.
The development
of detectable
lesions,
however,
is largely
determined
by the degree
of elongation
and modelling
which
the bone
undergoes
during
growth
; these
factors
are reflected
in the characteristic
differential

incidence

of lesions

at the

various

sites.

PATHOGENESIS

Of the

many

three warrant
MUller
(1914)
collections

theories

that

have

been

advanced

to explain

the

ofcartilage

that these
developed
Mullers
observations

cells

arising

from

into exostoses
and
have been confirmed

the proliferative

layer

ofthe

were due to a basic

by others
(Scherer

defect

of growth

of bone growth
and the associated
deformities
(1920)
noted
in radiographs
of patients
with

periosteum.

abnormality
1928, Jaffe

serious
objections
to his theory
of the pathogenesis
of multiple
far described
as showing
this phenomenon
have been adults,
occurs
in areas
that later
develop
exostoses.
Furthermore,
retardation
Keith

basic

serious
attention-those
ofM#{252}ller(l914),
Keith (1920) and Langenski#{246}ld
observed,
in the endochondral
bones
of a patient
with multiple
exostosis,

only
(1947).
small

He suggested

of the periosteum.
1943), but there are

exostosis.
All the patients
and it is not known
whether
this could
not account
for

which
multiple

have been
exostosis

described.
that the

so
it
the

cortical

density
invariably
stopped
short
at the metaphysial
deformity
(see Figs. 6 to 8). He believed
that a sleeve
of cortical
bone
extending
to the epiphysial
plate
was required
to confine
the
growing
cartilage
to its normal
dimensions
and prevent
undue
transverse
growth
; the absence
of this cortical
cuff would
leave
the epiphysial
plate
exposed
on the surface
of the shaft
and
free to give rise to irregular
outgrowths
or exostoses.
He suggested
that this was the

case

in multiple

endochondral
new bone
that

this

exostosis

and

attributed

the

abnormality

ossification
and longitudinal
growth
formation
at the periphery
of the plate.
is an abnormality

of epiphysial

growth

and

associated
skeletal
deformities.
Although
Keith
did not present
histological
ring of bone has,
in fact, been observed
in animals
zones

of the

epiphysial

plate

(Lacroix

1951).

human
bones
(Figs.
15 and 16). Histological
end of the femur
was carried
out in fourteen
healthy
subjects
who had died in accidents;
years.
The bony
sheath is particularly
well
subjects

it may

be altogether

to a lack

of coordination

between

at the epiphysial
plate
and subperiosteal
The most vital aspect
of Keiths
theory
modelling,

which

evidence
for
surrounding
The

same

account

for

is
the

his theory,
a perichondrial
the hypertrophic
and calcified

structure

and microradiographic
specimens
obtained
their
ages ranged
formed
in those

could

can

be demonstrated

in

examination
of the distal
at necropsy
from previously
from
six months
to eighteen
under
five years;
in the older

absent.
THE

JOURNAL

OF

BONE

AND

JOINT

SURGERY

HEREDITARY

This
bone

perichondrial

ring

encountered

essential
some

farther

for

normal

the

older

of

of bone

down

is simply

the

orientation

had

most

shaft

of epiphysial

advanced

and

there

growth

not

led

303

EXOSTOSIS

the

diaphysial

studied

subjects

MULTIPLE

edge

in humans.

to the

of the

is, as yet,

Certainly

irregularity

periosteal

no evidence
its

of growth

new
that

it is

absence

which

in
Keith

suspected.
Nevertheless

system

the

normally

growing

lesions

which

coordinates

cartilage

the

increases

its

been

have

parameters

described

do suggest

of cartilaginous

transverse

diameter

at

FIci.15
Figure
15-Photomicrograph
showing
the highly cellular
periosteal
hypertrophic
and calcified
zones at the periphery
of the epiphysial
radiograph
of the same region.
The periosteal
(membrane)
bone
advancing
trabeculae
of the metaphysis.

appositional
1955, Ham

growth
1957).

case:

the

that

from the
Langenskiold

epiphysial

overlying
(1947),

cartilage

of these
most
study
of

more

recent

This

concept

Mullers

disposes

peripheral
epiphysial
the

of

normally

cells.
growth

main

of whatever

It is generally
held
to the cell columns

expands
into
exostosis

by
the

interstitial

to Keiths

growth

proliferative
as a persistence

Support
for Langenskiolds
with
radioactive
tritiated

objection

theory

that
by

new bone adjacent

to the
plate.
Figure
16-Microextends
slightly
beyond
the

perichondrium
(Lacroix
1951, Weinmann
and
however,
presented
evidence
that the opposite

outermost
layer of cartilage
cells is transformed
He explained
the development
of multiple
property

a dysfunction

growth.
right
angles

and

and

Sicher
is the
that

the

layer of the periosteum.

of the chondrogenic
views has come
thymidine
(Rigal
is not

incompatible

from a
1961).
with

observations.
SUMMARY

I.
In

Hereditary
most

over
2.

exostosis

previous

records

characteristic
of cases

invariably
45 B,

has
were

been

studied

available

and

the

in fifty-six
progress

patients
and their
of the disease
could

relatives.
be traced

years.

many

The

series

VOL.

multiple

cases

are

produces
NO.

2,

noted.

lesions
are described
and
The disease
is inherited

detectable
MAY

1963

lesions

in the

the complications
in approximately

heterozygote.

encountered
two-thirds

in the present
of the cases and

304

L. SOLOMON

3. The
incidence

cartilage-capped
is closely
related

4. An attempt
likely theories

exostoses
to the

has been made

of the pathogenesis

are
growth

confined
potential

to the endochondral
of the sites involved.

to explain
the curious
distribution
of the disease
are discussed.

skeleton

of the

where

exostoses,

their
and

the

I wish to express
my gratitude
to Mr H. Jackson
Burrows
and Dr H. A. Sissons for their help in the preparation
of this paper;
to Dr C. 0. Carter
and Miss A. R. Buck of the Clinical
Genetics
Research
Unit, Great
Ormond
Street, for their patient assistance
in the studies on heredity ; to Mr S. Y. Au of the Institute
of Orthopaedics
for his advice on the estimation
of urinary
acid mucopolysaccharides
; and to Miss L. Stewart
of the Institute
of Orthopaedics
for preparing
the microradiograph
in Figure
16. I am grateful
to the Medical
Staffs of the
Royal National
Orthopaedic
Hospital
and the Hospital
for Sick Children,
Great Ormond
Street, for allowing
me to have access to their patients.
Figure 4 was provided
by the Photographic
Department
of the Middlesex
Hospital.
All the other photographs
were prepared by Mr R. J. Whitley ofthe Photographic
Department
of the
Institute
of Orthopaedics.
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Surgery,

G. E., and
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A. (1920):
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P. (1951):
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A. E. (1960):
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E. (1914):
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ihre

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E. C., ROSEVEAR,
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B. F. (1962):
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THE

JOURNAL

OF

BONE

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