MYOTONIC DYSTROPHY IN INFANCY AND CHILDHOOD

(1)

Philip R. Dodge, M.D., Ingrid Gamstorp, M.D., Randolph K. Byers, M.D.,

and

Patricia Russell, M.D.

Departments of Neurology and Pediatrics, Harvard Medical School

and

the Neurology and Children’s Services and Joseph P. Kennedy, Jr., Laboratories of the Massachusetts General

Hospital and the Neurology Service o,f the Childrens-Peter Bent Brigham Hospitals

(Submitted July16; accepted for publication September 2, 1964.)

Presented

in part to the New England Pediatric Society, September, 1961.

Dr.

Gamstorp

was

formerly

Jerry

Lewis

Fellow

of the

Muscular

Dystrophy

Association

of America,

Inc.,

and

Clinical

and

Research

Fellow in

Neurology

and

Pediatrics, Massachusetts General Hospital and Harvard Medical School. Dr.

Russell

was supported

by

N.I.N.D.B. No. 2B-5185.

This

work

was

supported in

part

by N.I.H.

Grant

No. 2B-5236.

ADDRESS:

(P.R.D.) Massachusetts General Hospital, Fruit Street, Boston, Massachusetts 02114.

3

PEDIATRICS, January 1965

M

YOTONIC DYSTROPHY

(dystrophia

myo-tonica)

is

thought

of

as

a disease

of

little

interest

to the

pediatrician

since

it is

generally

considered

to

be

asymptomatic

until

puberty

or

later.

This

feature

has

been

stressed

to

distinguish

myotonic

dys-trophy

from

myotonia

congenita

(Thom-sen’s

disease),

which

has

an

acknowledged

onset

early

in life.’

However,

over

the

years

a

number

of

cases

of

myotonic

dystrophy

beginning

in

childhood

have

been

report-ed.28

Thomasen,9

on

the

basis

of an

exten-sive

clinical

survey,

stated

that

more

than

half

of

the

patients

noticed

symptoms

be-fore

15 years

of age

and

concluded

that

the

disease

begins

most

commonly

between

the

ages

of 10 and

15 years.

Many

of the

young

patients

have

had

no

subjective

complaints

and

were

not

discovered

until

field

investi-gations

of

families

with

myotonia

were

car-ried

out.

This

observation

led

Maas

and

Paterson1#{176} to

emphasize

that

“pure

myo-tonia”

in children

and

young

adults

may

be

the

first

symptoms

of

myotonic

dystrophy,

the

complete

clinical

syndrome

evolving

in

subsequent

years.

Recently,

Vanier”

re-ported

6 cases

of myotonic

dystrophy

diag-nosed

in

infancy

and

childhood,

stressing

the

resemblance

of

certain

features

of

the

disease

in this

age

group,

to those

of

amyo-tonia

congenita

and

congenital

facial

diplegia.

In

the

9 infants

and

children

recorded

here,

the

diagnosis

of

myotonic

dystrophy

was

established

in

7 and

appeared

possible

in 2. The

patients

were

all

examined

during

a single

year,

although

in

several

instances

we

had

failed

to make

the

correct

diagnosis

on

an

earlier

examination.

In

all

but

one

case,

a family

history

consistent

with

myo-tonic

dystrophy

was

obtained

subsequently.

In

retrospect,

our

errors

resulted

primar-ily

from

lack

of

familiarity

with

the

varied

manifestations

of

the

disease

in

early

life

and

a failure

to consider

the

proper

diagno-sis.

Electromyography,

throughout

this

study

performed

with

concentric

needle

electrodes

and

a

Disa

electromyograph,

proved

to

be

of great

help

in orienting

our

thinking

correctly.

We

suspect

that

this

ex-perience

is

far

from

unique

and

that

the

disease

is more

often

symptomatic

in

early

life

than

is generally

appreciated.

It

is for

these

reasons

that

we

feel

justified

in

pre-senting

our

experiences

in some

detail.

Case

REPORT

OF

CASES

A 3-week-old boy was first admitted to the Chil-dren’s Hospital Medical Center on May 8, 1951,

because of difficulty in sucking and swallowing,

general inactivity and attacks of cyanosis. He

was

the

first-born

child

and

the

family history was

re-ported as negative. The second stage of labor was

prolonged

and

delivery

was

difficult,

requiring

(2)

in-effective and feeding was slow. Jaw closure was

P#{176} \Vlieii held upright there was ptosis of both (\(‘li(lS. Biceps tiid Patellar reflexes were obtained.

No test for mvotonia was made. At the age of 6

weeks, the patient was discharged with a diagnosis of cerebral damage secondary to a difficult birth.

lie was admitted to the hospital next at the age of 8 ears because of generalized weakness, a

fail-ure to progress in school, and (lifficulty with speech

and vision. At this time the mother, age 35 years, though she clailfle(l to be health, was shown to have mvotonia of grip hut no 1)ercussion niyotonia.

A diagnosis of muscular dystrophy had been estal)-lished earlier in two maternal uncles, age 50 and 51 ears. Another maternal uncle, a deaf mute, had been confined to an institution since early child-hood. One maternal aunt was well with two norulal children and another maternal uncle wa also well

but not nlarrie(l. The Illaternal grandfather had

bilateral cataracts. The pati(’nts father was a school

teacher and in good health. At the time of this admission, the patient had six siblings. A

6-year-old girl (Case 2) was examined at the same time 110(1 ShOVfl to have nivotonic dystrophy. The five

other children ranging in age from 2 months to 7 years were said to be healthy; they were not

cx-amine(l . On exaniination, the 1)1t1nt was diffusely weak with an expressionless face but no ptosis; his

jaw hung open most of the time and saliva drooled from the mouth (Fig. 1). His speech was lacking in expressive consonants and was difficult to under-stand, lie chewed with difficulty. Although the pa-tient was generally weak, the stemocleidomastoid,

deltoid and gluteal muscles were particularl’ af-fected. Percussion myotonia was easily

(lemon-strated in the deltoid muscles. Deep tendon reflexes

were normally active. Plantar reflexes were flexor.

Sensory examination was normal.

The left deltoid, left biceps brachii, and left quadriceps muscles were examined

electromvo-graphically. The biceps brachii and the quadriceps muscles showed no spontaneous activity and motor

unit potentials were normal in number, am-plitude, duration, and shape. Insertion of the needle

in the deltoid muscle, moving of the needle, or tap-ping of the muscle provoked typical bursts of myo-tonia. Motor unit potentials were normal in num-ber and amplitude, had a short duration, and the

proportion of polvphasic potentials was increased. Conduction velocity, measured in the left ulnar and median nerves, was normal.

An electrocardiogram was abnormal because of low voltage over the left precordial leads. An

oph-thalmological consultant saw flO cataracts and

at-tributed the visual difficulty to nwopia. A conduc-tive type of hearing loss was demonstrated in the left ear. An endocrine consultant considered the genitals to be average in size for the age.

The right deltoid muscle was biopsied. A few

FIG. 1. Case 1. Upper 2 photographs taken in the neonatal period. Note the drooping lids and

sag-ging lower face and lip. At 8 years of age, lower photographs, ptosis is no longer evident but

other-wise the facial appearance is basically unchanged.

Note the long thin neck.

fibers with densely packed chains of centrally

placed nuclei were seen (Fig. 6A).

Psychometric examination suggested that the pa-tient’s IQ was between 50 and 60.

Corn ment

The

feeding difficulty in early infancy is ex-plainable on the basis of weakness of facial and

)Ossibly other muscles. Weakness of the jaw

miis-des permitted the mandible to sag and with the facial weakness led to drooling and the character-istic facies of myotonic dystrophy, clearly evident at age 8 years. In the absence of obvious myotonia of facial muscles, as seen in Case 3, the ptosis in

in-fancy implies weakness of the elevators of the upper

lids. It is of interest that this had disappeared b

age 8, suggesting actual improvement in the

clini-cal

state.

A difficult birth with attendant asphyxia is not uncommonly followed by generalized hypotonia so

that

our

initial

misinterpretation

of the

findings

is

(3)

con-\Vas erroneously recorded as negative (luring the

first admission.

Case 2

A 6-year-old girl, the sister of Case 1, was

ad-nutted to the Children’s Medical Center for the first time n September 29, 1959. The mother reported

that the child was weak and cyanotic at birth and treated with oxygen for two weeks thereafter. She

remained in the hospital for over two months

be-cause of an inability to suck and swallow and had

to be tube fed. The sucking and swallowing

(lifh-culty persisted throughout infancy. All movem(’IIts

were weak and poorly co-ordinated. Development

was delayed. She held up her head at 10 months, walked alone at 2 years, and was toilet trained at 4 ears. At the time of examination, she was

attend-ing a school for retarded children. Speech was poorly articulated and the patient drooled

continu-ally.

On examination, the child’s face was weak and

expressionless. The jaw was small, hung open, and

saliva drooled from the mouth (Fig. 2). Her speech was unintelligible and lacking in explosive

con-sonants. Gait was waddling. There was generalized weakness of the muscles of trunk and extremities; the neck muscles were particularly weak. Percus-sion myotonia was demonstrated in the thenar

and deltoid muscles, but there was no rnvotonia on gripping with the hand. The tendon reflexes were normally active and there were no Babinski signs. Myotonic discharges were seen on

electronwog-raphy. An electrocardiogram was abnormal because

of an intermediate axis and low voltage in the standard and unipolar limb leads. An ophthalnio-logic consultant found no cataracts. Muscle fibers in the biopsy specimen of the gastrocnemius mus-cle varied somewhat in size and a few centrally

placed nuclei were seen but these changes were

minimal (Fig. 6B).

Cornrnent

Aside from absence of ptosis in early life this

girl’s illness closely resembles that of her brother.

Case 3

MCII. 1086585. A 6-week-old boy was ad-mitted to the Massachusetts General Hospital n

January 21, 1960, for evaluation of congenital

in-guinal hernias and a questionable abnormality of the shoulder girdle. The mother had had two nor-mal children previously and had no difficulty

dur-ing pregnancy, labor, or delivery. The infant

ap-peared normal in the neonatal period; but, al-though he sucked and swallowed well, he gained weight poorly. The patient was early noted to

re-1K;. 2. Case 2. Age 6 years. Facial app:arance

similar to that of her brother, Case 1. Note sunken temples, iml)assive facies, drooling, and thick neck.

sist passi\e abduction at the shoulders. The fam-ils history for neuromuscular disease was negative.

On examination bilateral indirect inguinal hernias

and a paucity of subcutaneous fat were note(l. His general responsiveness was normal for the age.

There was a suggestion of ptosis on the left and

curious intermittent stridor developed when startled. However, the larynx was normal on

di-rect examination and no abnormality was

demon-strated on barium swallow. The shoulder girdle ap-peared narrow and the shoulder muscles somewhat small but well delineated. All other muscles were

of good bulk and no definite weakness was noted.

The deep tendon reflexes were generally brisk and! the plantar responses equivocal. Moro and tonic neck reflexes were nornial for the age, and a normal

response to pin prick was demonstrated. On elec-tromvography spontaneous fibrillation-like poten-tials of a frequency high enough to give a “dive-bomber” sound and interpreted as nwotonia were obtained from the left deltoid! muscle. Fibrillation potentials, of a lower frequency and presumably normal for the age, were demonstrated in the left

trapezius, deltoid, and pectoralis major muscles. Normal conduction velocities were demonstrated in

the left median and ulnar, and right pro11e1l nerves.

No definite diagnosis was niade and the patient was discharged home. He returned! at 3 months of

age at which time a left herniorrhaph was

per-formed. A biopsy from the left rectus femoris mus-cle was considered normal. On this admission a

peculiar appearance of the eyelids, Periodic laryn-geal stridor, narrow shoulders, and hvpertrophy of the muscles of the extremities were commented upon by several observers. Wasting of the temporal muscles was also noted! at this time. Unquestion-able myotonic discharges were elicited on dcc-tromyography of the right deltoid and pectoralis

major muscles (Fig. 4).

(4)

plained. The severity and generalized extent of the

myotonia, its early age of onset, and the subsequent

hypertrophv of skeletal muscles is characteristic of mvotonia congenita but the temporal hollowing

suggests atrophy of temporal muscles and the diag-nosis of myotonic dystrophy. It seems likely that this diagnostic question will be resolved only by

repeated evaluation over a period of years. An-other disease associated with myotonia, paramyo-tonia congenita, was excluded from diagnostic con-sideration by the failure of precipitation of myo-tonia by cold, generalized muscle hypertrophv and

focal atrophy of muscles.1’

Case 4

Fic. 3. Case 3. Age 11 months. Blinking was

pre-cipitat(’d in the upper photograph by a bright flash

of light. Approximately 15 seconds later the lower

photograph was taken. Note the persisting p1rtial closure of eyelids caused by myotonia of the obicu-laris oculi muscles. Atrophy of temporal muscles

is also illustrated.

since the hermorrhaphy. Myotonia of the eyelids was striking; whenever he was startled by a loud noise or bright light, the eyes closed tightly and then slowly opened over a period of many seconds

thereafter (Fig. 3). In retrospect the father, a phy-sician, and the mother recalled having noted this

from early life. Exposure to cold did not aggravate

the mvotonia. Percussion of the extensors of the wrists elicited myotonic responses. No abnormal-ity of the shoulder girdles was noted. The infant

sat without support and no weakness or reflex

ab-normality

was

found.

Once

again

myotonia

was demonstrated in the left biceps, deltoid, and

an-terior tibial muscles on electromyography. Motor unit potentials were normal in number, amplitude, duration and shape.

Cornrnent

That this infant suffers from generalized myo-tonia seems definite. It is tempting to attribute the

stridor early in life to myotonia of laryngeal mus-cles. No inipairment of sucking, or swallowing,

noted in Cases 1, 2, 4, 5, 6, and 9, was observed,

and

the

failure

to gain

weight

could

not

be

ex-M.G.H. 1042893. A 3-year-old girl, sister of Case

5,

was born after a normal pregnancy, labor, and delivery. There was a history of difficulty in suck-irig and, during the early weeks of life, impassive

facies were first noted. Development, however, was

not abnormal-she sat at 6 months, stood at 10 months, and walked alone at 15 months of age.

First words were uttered at about 1 year of age.

She was always noted to walk peculiarly and was “pigeon-toed.” Motor skills had been gradually

im-proving but were sufficiently unusual to lead to a neurological examination at 2 years of age, when a diagnosis of muscular dystrophy’ was considered.

On examination the patient was an attractive

girl with impassive facies even during episodes of vigorous crying (Fig. 5). She was alert and scored

in the low-average range on the Stanford-Binet intelligence test.

Ocular niovements were normal, there was no ptosis and no lenticular opacities were seen. No

weakness of other muscles was

demonstrated

and

in

contrast to her brother she arose from the

re-cumbent position without difficulty. Tendon re-flexes were normally active and plantar reflexes were flexor. Sensation to pin prick was normal.

Myotonia could not be demonstrated on per-cussion of muscles but on electromyography there

were evident myotonic discharges in the left deltoid

and right biceps muscles. An increased proportion

of polvphasic motor unit potentials was also seen in these muscles. No electromyographic

abnormali-ties were noted in the left frontalis muscle. Nerve

conduction

velocities

(left

ulnar

and

median)

were

normal. A striking smallness in size of muscle fibers with considerable random variation in size was demonstrated in a biopsy specimen from the right

deltoid muscle.

Cornment

Bilateral

facial

weakness,

which

impaired

suck-ing

in early life, was evident from birth. There were no other definite clinical signs of disease

al-though

by history

gait

was “peculiar”

early

and

(5)

I,

I

s.w.

0’

_{3 mos.}

3-3--60

Right

Deltoid

lOmsec

FIG. 4. Electromyographic recordings from Case 3, demonstrating the spontaneously occurring high fre-quency myotonic discharges occasionally mixed with normal motor unit potentials.

It is easy to see

how

the

facial diplegia might be

mistaken

for the

Moebius

syndrome

as pointed

out

by Vanier.” The facial deformity, tpkal of myotonia dystrophy in older children and adults, had not developed or, possibly, was obscured by

“baby

fat.”

Case 5

M.G.H. 1008985. A 2-month-old boy, brother of Case 4, was admitted in February, 1958, for

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MYOTONIC

DYSTROPHY

Fic. 5. Case 4, age 3 years. The expressionless

facies are striking an(! similar in appearance to

those of her brother (Fig. 7).

kg). The patient was cyanotic in the neonatal pe-riod and! vet sucked better than his sister had!, He remained in the hospital for 5 weeks. Shortly after going home the patient became canotic after drinking some orange juice. He was treated for a few days with oxYgen an(l antibiotics and!

re-coverv was uneventful. Howeyer, he frequentls re-gurgitated half of his feeding and! was described by

his mother as a “lazy child.” Partial collapse of the right lung and eventration of the diaphragm were discovered during an outpatient re-evaluation of the patient. At that time a history of bilateral facial weakness in the older sister was recorded. Aside from an eventration of the right diaphragm and

questionable congenital deformity of the hips there were no relevant physical signs. Strength and

re-flex activity were deemed normal. The patient was discharged without treatment. He was seen next at

26 months of age for evaluation of hypotonia and slowness in motor development. The patient sat

alone at 7 to 8 months, stood with support at 12 months, and walked at 18 months of age. The family’ reported that he had great difficulty in

climbing stairs and could not run.

On examination he was a well-nourished boy

with moc!erately severe lumbar lordosis. The facies were impassive, the corners of the mouth sagged

and there was weakness of the temporalis muscles (Fig. 7). The remainder of the cranial nerves

func-tiOIl(’(! normally and! the lenses were free of

cata-ract. The patient could not arise from the

recum-bent position without rolling into the prone

posi-tion, kneeling, and then extending his legs at the

knees and hips and crawling up his legs with his

handls. There was no focal muscle atrophy and no

fasciculations were seen. Percussion of the exten-sors of the wrist elicited slight myotonia. The deep tendon reflexes were normally active, plantar

re-flexes flexor and pin prick sensation was normal. Pertinent laboratory findings included a normal

serum transaminase (35 units) and normal

electro-cardliograni. On electromographv, mvotonic

dis-charges were found in the right deltoid, biceps, and first interosseous muscles. In addition, many

poly-l)lasic motor unit potentials with short, sharp spikes were demonstrated in the right deltoid and biceps muscles. On muscle biopsy there was a

random distribution of large and small fibers. A nerve twig included in the muscle biopsy was

normal as were the conduction velocities of the left ulnar and median nerves.

The family history was recorded initially as nega-tive but the mother was noted to have bilateral

facial weakness, myotonia of grip, and percussion myotonia of thenar, wrist extensor, and tongue

muscles. There were no lenticular opacities seen on slit-lamp examination of the lenses. Typical myo-tonic bursts were demonstrated on electromyog-raphy. A maternal aunt was not examined but by

history clearly had the disease and there was a

history’ of cataracts in the maternal grandmother

and great-grandmother (Fig. 8).

Cornrnent

In addition to the early onset of facial weakness

and feeding difficulties, also experienced by the sis-ter, this patient’s general niotor development was

strikingly abnormal, and his performance on exam-ination indicative of proximal muscular weakness,

as is common in progressive muscular dystrophy. Nevertheless, there had been continued improve-ment, suggesting the syndrome of benign congeni-tal hypotonia.”

Elevation of the diaphragm in this case is of par-ticular interest for, as Caughey and Pachomov’4

have pointed out, this may be a feature of

myo-tonic dystrophy, but to our knowledge has not been demonstrated previously in a child with this disease. Its appearance so early in life adds cred-ence to the argument that it is probably an asso-ciated developmental defect. Unlike the usual case of total eventration in which the left side is almost

always involved the abnormality may affect either side or both.

Although details concerning the cataracts in

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dys-Fic. 6. (a) Longitudinal section of deltoid muscle, Case 1, showing chains of centrally placed nuclei. (b) Longitudinal section of gastrocnemius

mus-cle, Case 2, showing similar findings.

trophy. It is well known that cataract may exist as an isolated symptom of this disease, the fully

de-eloped syndrome appearing in subsequent gen-erations.

Case 6

P.A.D. 26-1280. This 93i-year-old boy was born one month before term after an uncomplicated preg-nancy, labor, and delivery. Birth weight was 2.4 kg. In the neonatal period he was noted to be generally weak, difficult to feed and was therefore kept in the hospital for a few weeks after birth. On several later examinations he was found to be slow in de-velopment, questionably stiff, without reflexes, and was considered to have an undetermined disease of central nervous sstem. At age 4 years he was

ad-mitted to the Paul A. Dever State School for the mentally defective. On his admission there he could neither speak nor walk. He subsequently acquired these skills and now attends classes for retarded

children.

No member of his family was available for

questioning or examination but both parents were said to be of limited intelligence and by de-scription the mother and maternal aunt have

myo-tonic dystrophy. The latter is a patient in a state mental hospital. Three siblings of the patient are

alive and said to be normal; one child was still-born.

On examination the patient was of limited in-telligence but alert and co-operative, lie

(8)

MYOTONIC

DYSTROPHY

Fic. 7. Case 5, age 2 years. Brother of Case 4 (Fig. 5).

meager vocabulary and poor articulation. No cata-racts were seen on slit-lamp examination. He was

of normal size for age with a markedly’ increased

lumbar lordosis and protruding abdomen. Both

testes were undescended. He had! an elongated face and sagging lower jaw (Fig. 9). There was bilateral

weakness of facial and temporal muscles and slight atrophy of the latter. Neck niuscies were of normal bulk and strength. Distal muscles of all four

ex-tremnities were atrophic and weak; mild weakness

was also noted in proximal muscles. Gait was slow,

waddling, and there was a bilateral foot-drop. Ten-don reflexes were sluggish and plantar reflexes were

normal.

Myotonia was apparent on handgrip and could

be elicted by tapping the tongue or any superficial

limb muscle.

Electrocardiogram was abnormal with a sinus tachycardia of 138 per minute and a first-degree

atrio-ventricular block (P-R interval 0.19 see). The QRS complexes were unusual with low R waves

and prominent S waves in left precordial leads.

Buccal smear showed a male chromatin pattern.

Electromyograms from several limb muscles showed

typical myotonic discharges; the number of motor unit potentials was normal, their duration was short, and the proportion of polyphasic potentials was

increased; the pattern was the same in all muscles

examined (Fig. 10).

Cornrnent

Despite an inadequate history it

seems

likely

that

the

feeding

difficulties

early

in life

were

a

consequence of the myotonic dystrophy. When seen at 9i years, the diagnosis was evident for the patient’s physical appearance was typical of the

fully developed form of the disease. And, in ad-dition to the prominent proximal and facial

weak-ness of the younger children with myotonic dys-trophy, this boy also showed distal atrophy and

weakness similar to that seen in adults, though the

sternomastoids were not affected. Grip and

(9)

2

$2

No disease

Cataracts (Not examined)

#{149}. Myotonic Dystrophy (Examined) Retrolental Fibroplasia

Myotonic Dystrophy(Not-examined)

One eye larger

than other

Difficulty

becoming pregnant

/‘ Propositus

FIG. 8. Family tree, Cases 4 and 5. Numerals beneath symbols give ages of propositus amid relatives at the time diagnosis established.

Case

7 M.G.H.

970094.

A 7-year-old

boy was first seen

in 1957 for evaluation of painful feet and weak legs.

The

mother

had

no myotonia

on hand

grip

but

she

was

without

facial

expression. The maternal

grandfather and uncle were said to have weak and painful legs. These symptoms began early in life and progression was minimal over many years. A diagnosis of progressive muscular dystrophy was

madle at another institution. The uncle was mentally retarded but no further historical details are

avail-able.

The patient’s early development was normal. He

had no difficulty feeding as an infant, walked by a

y’ear of age, and talked early. Several febrile

con-vulsions occurred between 1 and 2 years of age.

The

onset

of neurological

symptoms was

uncer-tain but he had always been clumsy and had

diffi-culty descending stairs. He ran with difficulty, tired easil’, and complained of pain in the feet with

ex-ercise.

On examination he was an obese boy with oval

face. Pes planus was present bilaterally. Mental status and cranial nerve functions were normal.

There were no cataracts. No weakness, atroph, or

fasciculations were present in the neck or arm muscles. There was weakness of the abdominal, hip

extensor and quadriceps muscles; this was most evident when he arose from the recumbent or

squatting positions or stepped up onto a chair.

There was no obvious atrophy and no fasciculations

were seen. Tendon reflexes were normally active, plantar reflexes were flexor, and sensation was nor

ma!.

Laboratory studies included a normal

electro-cardiogram, serum transaminase of 22 units, and normal electromyogram. Biopsy of the left quadri-ceps muscle was also normal.

The patient was considered to have a familial

myopathv of undetermined type, and he was

re-examined at intervals. By 1960, there had been no change in his neurological status but on electro-myography there was myotonia in the left

quadl-riceps, anterior tibia!, deltoid and first dorsal

in-terosseus muscles. Motor unit potentials recorded from these muscles and conduction velocities of the left ulnar, median and peroneal nerves were nor-mal.

Corn rn ent

A diagnosis of myotonic dstrophy was never

seriously considered until after the demonstration of myotonic discharges Ofl electromyographv 3 years after the initial examination. The failure to

(10)

ear-Fic. 9. Case 6, age 9 years. Facial appearance altogether typical of fully

developer! mvotonic dlvstrophy. The lumbar lordosis is striking but distal

ap-pendicular atrophy’ is slight.

her cannot be explained. Despite the atypical dhi5-tribution of the myopathy its lack of progression

over 3 years, its association with mvotonia, and the history of a relatively’ benign mvopathv in the

maternal grandfather and uncle seem most con-sistent with a diagnosis of mvotonic dystrophy.

Case

8

MCII. 1107701. This 10-year-old boy was ad-mitted for treatment of meningococcal meningitis.

During the examination mild ptosis, niore

pro-nounced! on the right sidle, was noted (Fig. 11). This was reporter! to be a congenital abnormality

and the paternal grandfather, father, and paternal uncle had a similar defect (Fig. 11). Careful his-tory and examination were negative for other

stig-mata of mvotonic dstroph, hut on electromyog-raphy a few myotonic discharges were fouiu! in

the left deltoid but not in the left biceps brachii muscle. Motor unit potentials were normal in both muscles. The findings were considered consistent with myotonic dystrophy but too slight to he

diag-nostic. Myotonia and short, sharp, polvphasic motor unit potentials were recorder! from the left deltoid, left biceps brachii, left extensor carpi radialis, and right deltoid muscles of the father, addling

sub-stance to this dliagnosis.

Cornrnent

In this case, the diagnosis of mvotonic dystrophy

appears possible, though far from established. It

(11)

F.M. 9yrs. 4-14-60 L. 1st

dorsal

interosseous

Spontaneous activity

[5OpV I-I

lOnisec

During contraction

IO.5mV

lOmsec

[50PV ii

SOmssc

Fic. 10. Electromvographic recordings from Case 6. A spontaneously’ occurring myotonic discharge is seen on the left and! at the bottom. Motor unit potentials are seen on the right, many of them are

poly-phasic and of short duration.

be considlered as a possible cause of congenital ptosis in childhood. Congenital ptosis may precede by several years the other symptoms of my’otonic

dy’strophv. Here it may’ have existed in at least two generations as an isolated symptom in much the same way as cataract did in the earlier generations

of the family’ of Cases 1 and 2, and 4 and 5.

Case

9

MCII. 1042.508. This 63-year-old boy was born

weighing 1.9 kg about 2 months before term; the mother’s pregnancy was complicated only by ankle

edema. During the neonatal period feeding diffi-culties created a serious problem. Sucking was nor-mal but unless he was fed very slowly’ he would choke. A poor appetite persisted! until the time of examination, the food being retained in his mouth without being chewed or swallowed. Choking oc-curred occasionally when he was forced to swal-low. In spite of these difficulties his physical and

mental development was normal and he was doing satisfactorily’ in the first grade of school.

He was brought to the hospital for evaluation

after a diagnosis of myotoiic dystrophy was

es-tablished in his mother. She was 37 years of age and had had slowly’ progressive atroph’ and vast-ing of distal musculature for 16 years. There were bilateral facial weakness, typical myotonic

dlis-charges on electromvographv of the left biceps brachii and quadriceps muscles, bilateral cataracts andohigomenorrhea. One of her three pregnancies ended in miscarriage. Other members of the family

were said to be healthy.

On examination the boy was found to be bright,

alert, and co-operative. He appeared to be of at

least

normal

intelligence.

General

physical

and

neu-rological examinations were normal, with the

ex-ception of sluggish gag reflex and poor movements

of the soft palate. Slit-lamp examination was not

performed

but

there

was

no

cataracts

seen

on

ophthalmoscopy. The left biceps brachii muscle was examined electromyographically. Typical my’o-tonic discharges were found; motor unit potentials

were within normal limits.

Comrnent

This is the only’ patient of the present series in

(12)

estab-N’IYOTONIC

DYSTROPHY

FIG. 11. Case 8, age 10 years; top panel, slight, bi-lateral ptosis is shown in photographs of the pa-tient and of his uncle (middle panel) an! father

(bottom panel).

lishedl earlier in an adhmlt member of the family.

The

patient was asmptomatic and without care-ful examination he would certainly have escaped

notice. In retrospect, the feeding difficulties in in-fancy may well have been a transient symptom of the disease, although they’ could! equally’ well have

been related to his prematurity.

COMMENT

The

pertinent

clinical

and

laboratory

data

are

summarized

in

Table

I. From

an

anal-ysis

of

these

data

and

from

published

re-ports,

three

clinical

syndromes

emerge.

The

first

is

clearly

dime

to

myotonic

dystrophy;

the

other

2 may

tentatively

he

viewed as

such:

I.

SYMPTOMATIC EARLY LIFE MYOPATHY

INCLUDING FACIAL DIPLEGIA, GENERALIZED

HYPOTONIA AND RETARDED MOTOR

DEVELOP-MENT:

This

syndrome,

exemplified

by

Cases

1, 2, 4, 5,

and

6,

l)egins

in

earliest

infancy

with

sucking

and

swallowing

difficulties

seemingly

related,

in large

measure

at least,

to the facial

diplegia.

In

Case

9, swallowing

difficulty was prominent although facial weakness was

not

described

and

not

noted

on

several

examinations

between

the

ages

of 4 and 6 years. The precise reason for

dysphagia

was

never

adequately

defined

and

inasmuch

as

myotonia

was

the

sole

finding

on

examination

we

have

elected

to

classify

it as group

II. In

every

instance

the

feeding

difficulty

gradually

abated.

This

change

with

age

most

likely

reflects

the

decreased

importance

of

sucking

in

the

securing of nourishment although the

dis-appearance

of ptosis

in Case

1 suggests

the

possibility of actual improvement in motor

function.

The

Moebius

syndrome

is

an

acknowledged

cause

of this

type

of feeding

problem

and

may

occur

in

the

absence

of

lateral rectus palsiesY Thus, it must cer-tainly be considered in the differential

diagnosis

to

be

excluded

by

the

associated

clinical

and

electromyographic

findings.

Varying

degrees

of generalized

weakness,

hypotonia,

and

retarded

motor

development

were

also

seen

in this

group

of cases.

In

con-trast

to

the

peripheral

distribution

of

mus-cle

weakness,

so

characteristic

of

myotonic

dystrophy in the

adult,

there

was

striking

involvement of trunk muscles with lumbar

lordosis

and

weakness

of

proximal

limb

muscles

giving

rise

to

a waddling

gait

and

difficulty

in

arising

from

the

recumbent

position.

In

no

instance

did

there

appear

to

be

worsening

of

motor

functions

with

passage of time, but rather improvement

was

the rule. Maturation of motor

mecha-nisms

seemed

to compensate

for

the

myop-athy

which

during

early

childhood

was

either

non-progressive

or

only

slowly

pro-gressive.

This

type

of proximal

weakness

of

legs

was

seen

also

in

Case

7,

but

a history

of

associated

facial

weakness

could

not

be

elicited.

These

clinical

features

probably

accounted

for

the

temporary

inclusion

of

two

of

our

cases

(4

and

5)

in

the

general

of

henigmi

congenital

hypotonia,

although

involvement

of

facial

muscles

is

uncommon

and

will,

when

present

in future

cases,

alert

us

to

consider

the

diagnosis

of

myotonic dystrophy.

The

myotonia

was

asymptomatic

in

this

(13)

demon-Case

6. Except

for

transient

ptosis

in

Case

1 this

symptom was notably absent in all of this first group. The typical appearance of the

lower

jaw

was

observed

in

Case

6 at

the

age

of 9 years,

but

when

this

first

appeared

could

not

be

determined

from

the

history.

It

seems

likely

that

this

deformity

resulted

from

weakness

of

jaw

muscles

during

the

growth period. That such weakness may exist from infancy seems well established in

this

case

material.

The

evolution

in the

facial

appearance

from

infancy

to

8 years

of

age

is well

documented

in

Case

1, and

by

age

6 years

his

sister

also

had

acquired

the

fa-cial

expression

of myotonic

dystrophy.

This

characteristic

facial

appearance,

as

well

as

the

atrophy

and

weakness

of distal

muscles

of

the

limbs,

was

observed

in the

mother

in

Cases

4 and

5 and

we

suspect

that

on

re-examination

in

adulthood

all

patients

in

this

group

will

present

the

fully

developed

syndrome. The commonly associated

find-ings

of cataract,

baldness,

and

gonadal

atro-phy

are usually accepted as developing in

middle

life,6’7

or

at

the

earliest

during

the

second

decade

so

that

their

absence

in

childhood

is not

surprising.

In

general,

the

mode

of

onset

and

pattern

of

clinical

find-ings

during

infancy

and

early

childhood

in

this

group

of

patients

agrees

well

with

those

described

by

Vanier.

II.

MYOTONIC DYSTROPHY MANIFESTED

SOLELY OR PREDOMINATELY BY MY0TONIA:

The

early

reports

of

Thomasen9

and

Maas

and

Paterson1#{176} serve

to

alert

us

to

a second

syndrome of myotonic dystrophy in early

childhood, namely, that in which myotonia

is the

first

symptom

or

sign,

other

expres-ions

of

the

disease

appearing

later

in

life.

Myotonic responses were demonstrated

electromyographically

at

18 days

of

age

in

Case

3. Symptomatic

myotonia

developed

only

a short

while

thereafter,

although

its

significance

was

incompletely

appreciated

until

age

11 months.

The

hollowing

in

the

temporal

regions,

indicative

of

small

tem-poral

muscles,

was

an

additional

finding

suggesting a diagnosis of myotonic

dys-congenita

arises.

We

agree

with

the

gen-erally accepted view that myotonia

con-genita

and

myotonic

dystrophy

are

sepa-rate

diseases,

genetically

distinct

and

with

only

one

symptom

in

common.8’

#{176}‘17, 18

J

a

young

child

with

pure

myotonia

or

with

mild

accompanying

symptoms,

the

signifi-cance

of

which

is hard

to

evaluate,

a

defi-nite

diagnosis

must

be

deferred.

Careful

examination

of

the

parents

is often

of

help

in

this

situation.

In

families

with

myotonia

congenita

the

penetrance

of the

gene

is high

and

its

manifestation

is

approximately

the

same in all affected members. Therefore, myotonia is as a rule demonstrable in one

of

the

parents.

Lack

of

other

symptoms

and

signs

is also

of

greater

significance

in

an

adult

than

in a young

child.

In myotonic

dystrophy,

on

the

other

hand,

penetrance

may

be

decreased

and

manifestation

may

vary,

so

that the symptoms and signs in the

gene-carrier

may

be

meager

and

easily

overlooked,

if not

specifically

sought.

When

careful

examination

of

the

parents

is

miss-ing,

one

may

consider

an

apparent

lack

of

positive

family

history

as

a point

in

favor

of

the

diagnosis

of

myotonic

dystrophy.

It

seems

appropriate

to

consider

Case

9 in

this

group.

He

was

asymptomatic

yet

myo-tonia

was

demonstrable

electromyographi-cally

and

thus

this

disorder

present

to

a

slight

extent

at

least.

When

the

mother’s

first

signs

developed

is not

known

but

she

was

also

asymptomatic

in

childhood

and

may

well

have

appeared

as her

son

did

at a

comparable

age.

III.

CONGENITAL PTO5I5 AS A

MANIFESTA-TION OF MYOTONIC DYSTROPHY:

The

syn-drome

of congenital

ptosis

may

represent

a

third

mode

of

presentation

of

myotonic

dystrophy

early

in

life.

Our

Case

8 would

seem

to be

such

an

example,

although

myo-tonia

was

not

prominent

even

on

electro-myographic study. However, the presence

of ptosis

in at least

three

other

family

mem-bers

and

definite

electromyographic

evi-dence

of

myotonia

in

the

father

would

tend

to

support

the

diagnosis.

It

should

be

(14)

tran-Case No. Age Age ()nset Diagnosis Disease Established Presenting Problem Feeding Difficulty infancy PIous Neonatal feeding difficulty Congenital Weakness Facial Muscles + “gpo-tonia infancy impaired Motor Develop-ment + S 4 Apparent Progre,,-sion Disease Present neonatal period, absent at 8 years

+

Mental Defect

+ Early 8 years

infancy

F:arly 6 years infancy

Early Suspected,

infancy 8 weeks

Early infancy

0 +

Neonatal feeding + 0 + + + 0 +

difficulty

abnormal muscles of shoulder girdle, inguinal

hernia

3 years

+ (myotonia of obicularis oculi)

Facial and generalized weakness 0 + + 0 0 0

+ + 0 0 +

(mild)

5

6

Early infancy

1 years Eventration diaphragm, slow motor development

+ 0 ₊ ₊ ₊ 0 ?

Early infancy

9 years Generalized weakness,

mental defect

+ 0 P

Bilateral age 9

years

P + 0 +

7 S 9 Infancy exact time Early infancy Early infancy

10 years Clumsy, weakness, and

pain in legs

0 0 ?

Bilateral

age 9

years

P 0 0

10 years Clumsy, weakness, and

pain in legs

0 0 0 0 0 0

6years No symptoms + Failed to gain weight. Choked and

aspirated (3

months of age)

0 0 0 0 0

MYOTONIC

DYSTROPHY

TABLE I

SUMMARY OF PERTINENT DATA FROM NINE CASES OF MYOTONIC DYSTROPHY IN INFANCY AND CHILDHOOD

(Continued on following page)

sient

neonatal

ptosis

in

Case

1,

this

sign

diagnosis

in

the

cases

presented

in

this

re-was

absent

in

the

children

of

Group

I. port.

The

common

finding

in

all

cases

with

ELECTROMYOGRAPHIC

FINDINGS

myotonia

was

spontaneous

bursts

of

fibril-It is important

to emphasize

the

role

that

lation-like

potentials,

the

frequency

of

(15)

Signs on Examination (‘linical Myolonia (‘ala-ract Erideni Endo- nine-pathy EMG Biopsy FKG ilelerant Family history

Bilateral facial, jaw, neck, and extremity (proximal >(listal) weakness

Bilateral facial, jaw, neck, and extremity

(proximal distal) weakness

+ Deltoid age 8 years

+

Peltoid and thenar

eminene, age 6 years 0 0 0 0 0 Myotonia Short. polyphasic motor unit potentials

Dystrophy; chains of aaron-lemma nuclei

Low voltage in left precor-dial leads

Disease in sibs of Case I Mother and two maternal

uncles

Bilateral cataracts in mater-nal grandfather

Myotonia

Normal motor unit

potentials Myotonia Normal motor unit potentials Variation fiber size; centrally placed muscle nuclei No abnormality low voltage Not done

Sibling (If (‘use I

Neg.

Myotonia, liolloweil

temples, large extremity muscles

+

Fae in e:trly in-fancy; percussion

arm before 1 year

0

Bilateral facial, trunk

and proximal extrem-ity weakness

+

Tongue and thenar eminence, age 3 years

0 0 Myotonia

Polyphasic motor unit potentials l)ystrophy Dystrophy Normal Normal

Sibling of Case 5. Mother has typical disease and

mater-nal aunt history of disease Cataracts maternal great

-grandmother and

grand-motler

Sitling of Case 4 Bilateral facial, trunk

and proximal extrem-ity weakness

+ ‘rone and thenar eminence, age I years

0 0 Moytonia

Short, polyphasic motor unit potentials

Bilateral facial, trunk and proximal distal

extremity weakness

+

Grip; percussion

tongue, forearm and thenar emi-nence, age 9years

0 0 Myotonia

Short, polyphasic

motor unit potentials

N0t done A-V block

Abn QRS

complexes

Mother and maternal aunt

have (lisease (listury only)

Trunk and proximal leg weakness

0 0 0 Myotonia

Normal motor unit potentials

No abnormality Normal Maternal uncle and maternal

grandfather “dystrophy” (history only)

Ptosis only 0 0 0 Normal motor unit

potentials Myotonia (slight)

Not done Not done Father and paternal uncle have ptosis. Myotonia in

fa-ther (EMG)

0 0 0 0 Moytonia

Normal motor unit potentials

Not done Not done Mother has disease (dystro-phy, myotonia, cataract, and premature menopause)