Muscular dystrophy (a clinical analysis of 126 cases).
Muscular dystrophy is a common, genetically determined disorder of muscle. However, Indian literature, on the subject is rather scant. Various attempts to classify this disorder have been made., However, there are a few cases which do not fit any classification. The present article is a documentation of our experience of 126 cases of muscular dystrophy, observed over a period of six years at the Department of Neurology, K.E.M. Hospital, Bombay.
One hundred and twenty-six cases of muscle dystrophy were admitted to the Neurology Department. Apart from clinical documentation and muscle charting, all these cases were investigated with conventional muscle histology and electro-physiological techniques. I.Q. was determined by Kamat's method. Attempts were made to exclude biochemical abnormalities when suspected. The cases were followed up and investigations repeated when needed.
[Table - 1] shows the frequency of different types of muscular dystrophy. It must be pointed out that the age at onset mentioned under various headings below are probably approximate as most of our patients did not even know their current age properly.
Duchenne muscle dystrophy
Of 68 cases of Duchenne muscle dystrophy two were females but neither had features of Turner's syndrome (one was karyotyped). Consanguinity in parents was found in but 5.3% of them.
Twenty-six cases had the onset of disease from the time they achieved locomotive milestones. Twenty-one started walking normally but had the onset of the disease before 5 years of age. Twenty-one had onset of disease between 5 and 8 years. The mean age of onset was seen to be 6 years. Patients were disabled to grade VI-VIII by a mean age of 9.7 years. The onset of disease was found in pelvic girdle musculature in 91%. Interestingly, 2 cases manifested onset with crural muscle weakness and one with calf hypertrophy.
The distribution of muscle weakness is central to this disorder. In 56.5% of cases, weakness was global. These were advanced cases. Of the remaining 43.5%, all had pelvic girdle weakness, 941 had shoulder girdle weakness, and 33% had distal muscle weakness, 18% of the latter showing leg weakness and 15% showing forearm weakness. The brachioradialis was a frequently affected muscle. Facial weakness was seen in 29%; of these 75% were associated with the advanced form of disease. Hypertrophy was seen in the calves in 97.5% of the cases; 15.8% had gluteal, 10.5% each had deltoid and triceps and 9.2% had quadriceps hypertrophy. Mental backwardness was psychometrically confirmed in 17% of cases, though it was clinically suspected in 25%.
Serum total creatine phosphokinase (C.P.K.) was found elevated in 94%. Electromyogram was myopathic in 91.5% and E.C.G. showed an R/S ratio of more than 1 in right ventricular leads in 63.8% of cases. Muscle biopsy was consistent with the clinical diagnosis in 95%. E.E.G. was abnormal in 53.5%. Neurogenic involvement was thus evidenced by 53.5% of E.E.Gs. being abnormal and 17% of patients showing mental retardation. Nerve conduction velocities were normal in all.
Most of our findings in this group of patients agree with published data, though mental backwardness was seen less often than is reported in the literature., This might reflect socio-linguistic heterogeneity of the population to which one standard test was applied. E.E.G. was abnormal in 53.5% of our cases; this corroborates another study.
Of 14 cases of Becker dystrophy, all were males and only one was born of consanguineous parentage. The mean age at onset was 13.5 years. The patients were disabled to grade III by an average age of 18.3 years. Twelve had onset of symptoms in the hip girdle. One case presented with calf hypertrophy and one with toe walking at onset. No patient was mentally backward. The face was involved in one case. Hip muscles were involved in all cases and the shoulder girdle was affected in 13 cases. Nine cases (63%) showed hypertrophic calves; this high frequency is in agreement with other reports. Mean serum C.P.K. was elevated (7 times the mean in normals) in 12 out of 14 cases. E.M.G. was myogenic in all cases. Muscle biopsy was diagnostic of dystrophy in all cases studied. The F.C.G. was normal in all cases.
We observed 12 cases of benign, nonmyotonic non-facioscapulohumeral, girdle dystrophy. None had familial occurrence of dystrophic muscle disease, either clinically or on investigation. Three cases were females. The average age at onset was 16.5 years. All progressed to a disability of grade IV by 22 years. The pattern of muscle involvement was typically that of the Becker or autosomal recessive childhood dystrophies. In a well developed case, the pelvic girdle was more involved than the shoulder girdle. In the pelvic girdle, the adductors, abductors, internal and external rotators, gluteus maximus, quadriceps femoris and biceps femoris were affected. Amongst these, gluteus maximus and quadriceps femoris were the weakest. In the shoulder girdle, all muscles were usually involved, with the serratus anterior and triceps being the most affected. Involvement of face or heart or low intelligence was not observed, and hypertrophy was rare. Biochemical and electrophysio-logical investigations supported the clinical diagnosis (Mean elevation of CPK: 6.5 X mean in normals; electromyography showed myogenic pattern). Muscle biopsy was diagnostic of dystrophy in all the case.
This is a heterogenous group which has new been subdivided into several types. The feature common to all of them is onset with involvement of either shoulder girdle or hip girdle muscles. Many of the cases are non-familial. The existence of this entity has now been questioned. It is believed that most of these cases resolve themselves into (i) Becker dystrophy in males. (ii) Duchenne dystrophy manifestations in female carriers (the prevalence of these cases approximates than of undifferentiated limb girdle dystrophy). (iii) Autosomal recessive dystrophy of childhood (iv) Various scapuloperoneal syndromes. (v) Spinal muscular atrophy with secondary myopathic changes; and (vi) A variety of genetic or acquired myopathies.
Bacon and Smith described a family with girdle dystrophy of late onset with involvement of the upper limb girdle earlier and more marked than the lower limb girdle. Schneiderman et al detailed a large kindred with several members manifesting late-onset dystrophy of both girdles simultaneously, without facial involvement or hypertrophy, associated with the Pelger Huet anomaly. These cases began disease around the 4th decade and were significantly disabled by the 6th-8th decade.
Our cases of girdle dystrophy were all sporadic. They were younger than those of Bacon and Smith and those of Schneiderman et al. They progressed to disability grade IV by the age of 22 years, rather like Becker dystrophy. Further, under observation, the patients developed involvement of the two girdles sequentially (within 5 years) rather than simultaneously. Our patients already had the disease for 2-15 year's when first seen by us; their disability ranged from grade III to grade IV. Our patients did not belong to the scapulohumeral or scapuloperoneal syndromes. Muscle biopsy ruled out polymyositis.
Our patients, therefore, do not fit into any of the six types mentioned above and would justifiably bear the label of sporadic girdle dystrophy. Long term follow up, repeated family screening and data from other centres might allow them to be uniquely defined or re-classified.
Autosomal recessive dystrophy of childhood
We observed 4 cases of autosomal recessive dystrophy of childhood. All 3 males had their sisters and the one female had a brother similarly affected.
The mean age at which a disability of grade V was reached was 28 years. All cases had the onset of the disease in the hip girdle though at the time of examination all cases had involvement of both girdles. None was mentally dull. Hypertrophy was not seen in any case. Serum C.P.K. was elevated in all cases (mean = 6 X normal). E.M.G. was myogenic in all. Biopsy was diagnostic of dystrophy in all cases studied and E.C.Gs. were normal in all.
Of 11 cases of this type of dystrophy, 10 were males. No consanguinity was found in the parents of these cases. The mean age at onset was 19.6 years. The onset of weakness was noted in scapulohumeral distribution in 8 cases and in the face in 3 cases. Of the latter, 2 manifested weakness of eye closure and one of perioral muscles as the initial symptom. All showed scapulohumeral weakness. Six cases had, in addition, pelvic or peroneal weakness while 4 had weakness of both pelvic and peroneal muscles. All had facial weakness. Hypertrophy was seen in 2 cases, both in the deltoids. Intelligence was found normal in all. In addition, two had sternomastoid and trapezius weakness and one had only trapezius weakness.
Investigations revealed elevated serum C.P.K. values (mean 2.6 X normal) in 50% with the rest showing normal values. E.M.G. was myogenic in all patients. Muscle biopsy was consistent with the diagnosis in 9 cases and was normal in two. No clinical associations of any significance were observed.
Myotonic muscular dystrophy
There were 14 cases of myotonic muscular dystrophy. All were adult males with a moan age of 23 years at the onset of disease. On an average, 7 years elapsed between the onset and presentation of these cases.
The onset of disease was myotonic (grip) in 8 cases and non-myotonic in 6 cases. In the latter group, the symptoms at onset were either weakness of limb musculature (5 cases) or nasality of voice (1 case). All these patients with a nonmyotcnic onset developed myotonia within approximately the next 3 years.
Higher functions were normal in all cases. Five had facial involvement and 4 had alteration of voice. Sternomastoids were involved in 2 cases and chewing affected in 1 case. Twelve cases had involvement of the grip and 3 cases had tongue involvement while 1 case had myotonia in both. The disease was advanced in 6 cases, all of whom showed global muscle weakness. When muscle weakness was non-global, all had hand weakness. Non-myopathic features included cataracts in 6, baldness in 6, testicular atrophy in 4, small pituitary fossa in 4, diabetes mellitus in 1, goitre in 1 and gynaecomastia in 1.
Investigations showed elevated serum C.P.K. in half of the cases. E.M.G. was consistent with the diagnosis in 89% and muscle biopsy was diagnostic of dystrophy in 2 cases, all the rest being normal. One case showed an intraventricular conduction defect on E.C.G. while 1 case shoved borderline biventricular hypertrophy.
The only feature worth elaborating here is that 57% of our cases had a myotonic onset. Walton reported a myotonic onset in 1/3 of patients. Forty-three per cent of our cases with a non-myotonic onset developed myotonia on an average within 3 years of the onset of the disease. Our other findings are in agreement with the accepted features of the disease.
Scapulohumeral and scapuloperoneal dystrophies
This group comprised three cases with no departure from the features described in the literature.,
Sincere thanks are offered to the Dean, K.E.M. Hospital, Bombay, for permitting publication of this material and for his continued interest in clinical research; and to the residential staff, past and present, for their continued care of these and other dystrophies.