THE SPECTRUM OF MYOPATHIES I N THE CITY
OF SÃO PAULO
JOSÉ A . L E V Y * ABRAM TOPCZEWSKI *
LUCIA IRACEMA Z . DE MENDONÇA * M A Y A N A ZATZ *
R U T H B L A Y LEVISKY *
H a v i n g studied muscular diseases for the past 15 years at the N e u r o -logic Clinic of the Medical School of the University of S ã o Paulo, w e started a "study group", composed of neurologist, electromyographists, pathologists, geneticists and biochemists, and created an out-patient clinic specially for the treatment of these patients. Reviewing the studied cases w e found a total number of 466 patients ( T a b l e 1 ) . However, the cases of myatenia were not studied in depth, since this w a s done b y Prof. José Lamartine de Assis.
W e do not intend to discuss whether some of the types of diseases reported in this paper are actually and truly cases of myopathies, since at
this stage of events — and due to the daily progress made chiefly through
histochemical and electronic microscopic studies — there is much confusion
on the subject ( K i n g Engel, 1971)
3.
of the tests which are considered essential in the diagnosis and also because
many of the patients did not return for other consultations.
T h e criterion used in the diagnosis was clinic, genetic, electromyographic,
biochemical ( C P K , G O T , G P T , L D H ) , histopathological and
electrocardio-graphic.
C A S U I S T I C
A s can be verified in table 2, e x c l u d i n g the cases of myastenia and E a t o n L a m b e r t syndrome, w e h a v e 226 cases ( 7 0 % ) w i t h a confirmed diagnosis and 93 cases ( 3 0 % ) w i t h a p r o b a b l e diagnosis, w i t h a total of 319 cases. A m o n g the cases w i t h confirmed diagnosis w e h a v e 179 cases ( 7 9 % ) of progressive m u s c u l a r trophies ( P M D ) ; 19 cases ( 8 % ) of polymiositis; 19 cases ( 8 % ) of myotonic dys-trophy; and 9 cases ( 3 % ) of other disorders.
I n c o m p a r i n g the numbers of table 2 w e can see that for those cases not t i o u g h l y studied the diagnosis is h i g h l y p r o b a b l e . This is also verified in relation to o u r study of several forms of P M D ( T a b l e 3 ) , w h e r e w e find 179 confirmed and 83 p r o b a b l e diagnosis w i t h a total of 262 cases, the f o r m e r being thus distributed: 111 cases of D u c h e n n e ( 6 2 % ) ; 18 cases of Becker ( 1 0 % ) ; 39 cases of limb girdle ( 2 1 % ) ; 8 cases of facioscapulohumeral ( 4 % ) ; 2 cases of congenital ( 1 % ) ; and 1 case of o c u l o p h a r i n g e a l ( 0 , 5 % ) .
In the cases w i t h a confirmed diagnosis of P M D nothing important w a s shown in the enzymatic activity, but the fact that the C P K w a s increased in all the cases; this w a s not the case w i t h the G O T , G P T and L D H . T h e electrocardiographic studies ( T a b l e 4 ) , h o w e v e r , showed v e r y interesting results, since a v e n t r i c u l a r o v e r l o a d w a s found in 30 out of 33 cases of D u c h e n n e ( 9 0 % ) a n d also because in only one of these cases the test resulted n o r m a l ( 3 % ) . A v e n t r i c u l a r o v e r l o a d w a s found in 4 of the 7 cases of B e c k e r ( 5 7 % ) , w h e r e a s in the other forms the tests usually resulted n o r m a l . E l e c t r e n c e p h a l o g r a p h y resulted n o r m a l in 28 out of the 31 cases studied ( 9 0 % ) .
A s to the familial character part, it w a s present in 60 out of the i l l cases of Duchenne; in 15 of the 18 cases of Becker; in 18 of the 39 cases of limb girdle; in 6 of the 8 cases of fascioscapulohumeral; in the one case of o c u l o p h a r i n g e a l ; and in none of the congenital cases.
A m o n g the cases of Duchenne, six patients w e r e of female sex; and of these six cases, in three there w e r e manifestations of this disorder in heterozygous p a -tients ( t w o mothers a n d one sister, carriers of the g e n e ) and this could be explained by Lyon's theory. T h e other three seem to be D u c h e n n e cases w i t h a n autossomic c h a r a c t e r .
E l e c t r o m y o g r a p h y results w e r e compatible w i t h P M D in all of the confirmed cases; as for the muscle biopsy, the results w e r e compatible w i t h P M D in 62 out of 64 cases of D u c h e n n e ( 9 6 % ) ; in all the cases of limb girdle, fascioscapulohumeral, congenital and o c u l o p h a r i n g e a l ( 1 0 0 % ) .
In the cases of polymyositis the muscle biopsy results w e r e compatible with this disorder in 14 cases out of 19 ( 8 3 % ) ; in three of them the biopsy w a s typical of P M D and in t w o cases it w a s n o r m a l . A s for the electromyography, the results suggested polymyositis in half of the cases; the other h a l f w e r e typical of P M D .
Genetic Counselling — I n order to o r g a n i z e the Genetic Counselling Service
aspects: a ) confirmation or establishing of diagnosis; 6 ) s u r v e y of h e r e d o g r a m in as comprehensive a w a y a s possible; c ) use of t h e test m a d e for m e a s u r e m e n t of C P K enzyme activity in the blood s e r u m f o r defining diagnosis of the affected person, as w e l l a s f o r detecting h e a l t h y carriers of the gene of the D u c h e n n e a n d Becker types of P M D ; d) definition of types of heredity found in the a n o m a l y ; e ) estimate of the affection's recurrence risks; / ) orientation of families t h r o u g h Genetic Counselling itself.
M u r p h y et a l , (1966;5
, E m e r y a n d M o r t o n (1968)2
, E m e r y et al. (1967)1
, M u r p h y a n d M u t a l i k (1969)«, L e v i s k y ( 1 9 7 3 )4
; a n d Z a t z 1973)7
, h a v e reported on the impor-tance of a statistical method for estimating the total risks of a w o m a n b e i n g the c a r r i e r of a X l i n k e d g e n e . Besides t a k i n g into consideration the consultant's p o -sition in the g e n e a l o g y , such a method utilizes results of the test o£ detection of carriers by m e a n s of biochemical dosage of C P K . I t is k n o w n that one third of evident heterozygotes w i l l s h o w n o r m a l results, w h e r e a s only 5% of n o r m a l w o m e n w i t h no record of D u c h e n n e type P M D in the f a m i l y w i l l show a n increased C P K r a t e .
A combination is made, of these different types of d a t a , t h r o u g h the B a y e s method, f o r e v a l u a t i n g the probabilities of a w o m a n being the carrier of the P M D g e n e ( L e v i s k y , 1 9 7 3 )4
.
C P K dosages w e r e done in o u r l a b o r a t o r y for a l l patients affected b y the different forms of P M D , a n d also for m a n y of their relatives, specially mothers a n d sisters of patients suffering from P M D ( Z a t z , 1973)'. T h e method chosen for d o s a g e of C P K in the blood s e r u m is described in B u l l e t i n 520-80/F, published by S i g m a Chemical C o m p a n y (1967), a n d a l l o w s for the discrimination of the f o l l o w i n g scale of v a l u e s : normal: 0 to 12 S i g m a U n i t s ( U S ) per m l . of serum; borderline:
12 to 20 U S p e r ml. of s e r u m ; increased: o v e r 20 U S per ml. of s e r u m .
A r r o u n d 160 families of patients affected by the v a r i o u s types of P M D received orientation as to G C .
I n 1970, five adolescent heterozygotes b e t w e e n 12 a n d 18 years of a g e , w h o h a d a n increased C P K dosage (characteristic of female c a r r i e r s ) , received psycho-logical help before they faced G C .
D I S C U S S I O N
T h e evidence of 466 cases of myopathies, in a total of almost 100.000 out-patients of the N e u r o l o g i c a l D e p a r t m e n t of the Medical School of the University of S ã o P a u l o constitutes in itself d a t a to demonstrate the impor-tance of these affections.
According to all authors, P M D w a s the most frequently found myo-pathy in this research-work, the second being myasthenia gravis. T h e low n u m b e r of polymyositis cases can be explained by the fact that attention to this affection w a s only called, in our milieu, in the last ten y e a r s .
A m o n g the complementary tests, stress should be given to electrocardio-graphs, which w e r e a b n o r m a l in 32 out of the 33 cases of the Duchenne form of P M D , and to the C P K , which w a s increased in all confirmed cases of P M D .
S U M M A R Y
A review of all myopathic patients treated at the Neurologic Clinic of
the Medical School of the University of S ã o P a u l o during the past 15 years
is reported. A total of 466 cases w e r e examined and distributed as follows:
56% of progressive muscular dystrophy; 31% of myasthenia gravis; 6% of
polymyositis; 4% of myotonic dystrophy; and the remainder of several
diffe-rent diseases (central core disease, Kearns-syndrome, myotonia congenita,
adynamia episodica hereditaria, diabetic myopathy and E a t o n - L a m b e r t
syn-d r o m e ) . Enzymatic syn-dosages, electromyography, muscle biopsy, electrocarsyn-dio-
electrocardio-graphy and genetic counselling are also reported.
R E S U M O
Os autores fazem uma revisão de todos os casos de miopatias tratados
na Clínica Neurológica da F . M . U . S . P . durante os últimos 15 anos. F o r a m
examinados 466 casos, assim distribuídos: 56% de distrofia muscular
progres-siva; 31% de miastenia g r a v e ; 6% de polimiosite; 4% de distrofia miotônica
e, o restante, de várias outras moléstias (Central core disease, síndrome de
Kearns, miotonia congênita, adinamia episódica hereditária, miopatia
diabé-tica e síndrome de E a t o n - L a m b e r t ) . São relatadas também as dosagens enzi¬
máticas, eletromiografia, biópsia muscular, eletrocardiografia e
aconselha-mento genético.
R E F E R E N C E S
1. E M E R Y , A . E . H . ; W I L K I N S O N , E . & M U R P H Y , E . A . — Genetic counselling in. Duchenne m u s c u l a r dystrophy. Proceedings 2n d
I n t e r n a t i o n a l Congress of N e u r -o p h t h a l m -o l -o g y , M -o n t r e a l , 1967. E x c e r p t a Medica F-oundati-on, A m s t e r d a m , 1969,
v.
1, p. 106.2. E M E R Y , A . E . H . & M O R T O N , R . — Genetic counselling in lethal X - l i n k e d disorders. A c t a Genet. Stat. M e d . ( B a s e l ) 18:534, 1968.
3 . K I N G E N G E L , Z . W . — Classification of n e u r o m u s c u l a r disorders. In Daniel B e r g s m a — T h e Clinical Delineation of B i r t h D e f e c t s . W i l l i a m s and Wilkins, Baltimore, 1971, pp. 18.
4. L E V I S K Y , R . B . — Estudo genético e aconselhamento em distrofias m u s c u l a r e s p r o g r e s s i v a s . Tese de doutoramento, D e p a r t a m e n t o de Biologia, Instituto de Biociências da U S P , São P a u l o , 1973.
5. M U R P H Y , E . A . ; M U T A L I K , G . S . & E L R I G E , R . — T h e application of B a y e s i a n methods in genetic counselling. Proceedings 3r d
I n t e r n a t i o n a l Congress of H u m a n Genetics, Chicago, 1966.
6. M U R P H Y , E . A . & M U T A L I K , G . S . — T h e application of B a y e s i a n methods in genetic counselling. H u m . H e r e d . 19:126, 1969.
7. Z A T Z , M . — A t i v i d a d e d a creatinina-fosfoquinase ( C P K ) e estudos de ligação em distrofias m u s c u l a r e s progressivas de h e r a n ç a l i g a d a ao X . Tese de douto-ramento, D e p a r t a m e n t o de B i o l o g i a , Instituto de Biociências da U S P , São P a u l o , 1973.
