Muscle Diseases in India

Awide spectrum of myopathies is routinely encountered in India. The clinical load of these patients is shared to a large extent by paediatricians and physicians and a proportion of these patients are then referred to the neurologists for further evaluation. This is not surprising as the number of neurologists servicing the large population of India is only just over a thousand [1]. Lack of availability of large scale laboratory facilities, especially in the fields of immunocytochemistry and genetic testing limits the molecular analysis of those myopathies seen in India and hence the available data may not be representative of the true situation. Also most of the prevalence data are based on hospital series and are not population based.

Muscular dystrophies

The most common muscular dystrophies are Duchenne muscular dystrophy (DMD) and limb girdle muscular dystrophy (LGMD). Of the 1950 patients studied by Das 2 , 27.4% were muscular dystrophies with 30% having DMD and 29.2% LGMD subtypes. In a tertiary neuromuscular center in Mumbai, DMD formed the main myopathy of childhood while limb girdle dystrophy was the most common diagnosis of adolescent and adulthood myopathies.

Duchenne Muscular Dystrophy: This is by far the most common muscular dystrophy. Though no ethnic variations have been observed, one hospital based study suggested a higher prevalence among certain Hindu communities [3]. The phenotype of DMD has been studied in detail by a number of investigators. The differential muscle wasting and hypertrophy giving the ‘Valley sign’ as described by Pradhan [4] can aid the diagnosis of DMD/BMD patients in cases without calf hypertrophy or late presentation. Due to the prevalent religious concepts and illiteracy, more than one case of dystrophinopathy in a family is not too uncommon in India. In general, familial cases with DMD seem to follow similar clinical courses but on occasions, striking intra-familial phenotypic variability has been see (Figure 1). For example, one family has been described in which three brothers were suffering from a dystrophinpathy; one with a DMD phenotype, the second with a BMD phenotype and the third cousin had only cramp-myalgia syndrome [5].

Gene studies In dystrophinopathy: Multiplex PCR has been used to study the dystrophin gene in many centres in India and information is available from large centres in the north, west and south of the country. The deletion rates have been consistently around 70% [5-8], with the deletions being seen in the central and proximal hot spots of the dystrophin gene. In one study, the proximal deletions were essentially seen in the familial cases and sporadic patients tended to have deletions in the central hot spot [5]. An interesting phenomenon of double deletions has also been noted. These patients have two non-continguous hot spot deletions in the dystrophin gene. The significance is not clear as there are only few reports in the world literature [5]. Becker muscular dystrophy has been genetically analysed and the frame shift hypothesis seems to hold true in the majority of patients.

Rehabilitation: Due to a lack of awareness of muscle diseases, parents of affected children often do not know where to seek help. Illiteracy is also an issue which makes counselling difficult. The social structure in India is also not kind to the physically challenged with no availability of ramps for public modes of transport. Home rehabilitation programs [9], designed for those patients who cannot come for regular visits, has proved to be more successful than clinic based programs, in Mumbai and other centers. DMD-look-a-likes (Phenocopies): Information on the myopathies presenting in early life with a DMD phenotype is scarce. Case reports of a severe childhood autosomal recessive muscular dystrophy [SCARMD] phenotype with immunohistochemical characterisation are available [10]. A series of adhalinopathy children has also been reported from the south of India. An unusual family with severe autosomal recessive muscular dystrophy with mental retardation and chorea has been documented as well [10].

Limb Girdle Muscular Dystrophy: LGMD is the most common muscle disease seen in the adult population. Sarcoglycanopathies and dysferlinopathies have been characterised.

Sarcoglycanopathies: The age at onset and tempo of the disease show a lot of variation. Proximal pelvic girdle involvement with later involvement of the shoulder girdle appears to be the most common phenotype. Due to severe involvement of the hip adductors and relative sparing of the hip abductors, the hip abduction sign has been observed [11]. Three series have been reported on this condition, with multiple sarcoglycan deficiencies most often being seen on the immunocytochemical studies [11,12,13]. In northern India, gamma sarcoglycan deficiency has been found to be more common.

Genetics of sarcoglycanopathies: There is as yet very little information available on the genetic aspects of sarcoglycanopathies. In a study from Mumbai, 16 patients were found to have abnormalities in the sarcoglycan genes. In this small study, the most common abnormalities were encountered in the gamma sarcoglycan gene, followed by alpha, delta and a single instance of a beta sarcoglycan gene defect. A noteworthy point was the prevalence of the 525delT deletion mutation amongst those with the gamma SGP abnormality. This mutation is seen in select Mediterranean populations and its appearance in Western India is curious. It may relate to the pattern of human migration or may simply reflect a hot spot region in the gene.

Dysferlinopathy: Data on dysferlinopathy is lacking with only one series of 14 patients having been reported [14]. Nine patients had a distal presentation with calf atrophy. ‘Calf head on a trophy’, an appearance resulting from focal muscle wasting [15] and the diamond sign [16] were described in those with dysferlinopathies by Pradhan, emphasising the focal and patchy wasting of various muscles. Large scale genetic data is not available and case reports have shown a variety of genetic abnormalities within the dysferlin gene.

Other muscular dystrophies: Facioscapulohumeral dystrophy (FSHD) is not uncommon but published data is scarce. In a series of 211 cases of muscular dystrophy, Srinivas [17] saw only five (2.3%) patients with FSHD and Das2 in only 8 (1.3%).The differential wasting in certain muscles with relatively preserved bulk or mild hypertrophy of the muscles around the shoulder girdle describes the ‘poly hill sign’ of Pradhan [18]. Myotonic dystrophy is less common in India. Gourie Devi [19] found myotonic dystrophies to form only 8% of all muscular dystrophies. Basu et al has studied the CTG repeats in these patients with myotonic dystrophy and found similarity in the molecular anatomy of 90% of the Indian patients with Caucasians. In the remaining 10%, the expansion of the CTG repeat was of a new haplotype suggesting a unique founder effect probably indigenous to the Indian population [20].

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Congenital myopathies: In a study from Bangalore, 100 cases of congenital myopathies (CM) were diagnosed over a period of 20 years and the spectrum of CM consisted of centronuclear myopathy (39), congenital fiber type disproportion (35), central core disease (9), multicore disease (7), myotubular myopathy (5), nemaline myopathy (4) and one case of congenital myopathy with tubular aggregates. In a north Indian study, 4 nemaline myopathy cases out of 15 were identified [21].

Mitochondrial myopathy: Case series of mitochondrial myopathies have been published. In a large study from Hyderabad [22], the most common clinical syndrome associated with ragged red fibres (RRFs) on muscle biopsy was progressive external ophthalmoplegia with or without other signs. Kearns-Sayre syndrome and myoclonic epilepsy with RRFs was seen less often.

Osteomalacic myopathy: Though it is less common at present in India, Irani [23] reported 15 female patients of whom eight had constantly worn the burkha when outdoors. Notably these patients were multiparous with prolonged periods of lactation. The striking features were bone pains and pelvic limb girdle weakness.

Inflammatory myopathies: All types of inflammatory myopathies are encountered [24,25,26] although of interest is that inclusion body myositis is rare. Gayathri [27] reported five patients (four sporadic and one hereditary), and all had progressive muscle weakness with spared cranial nerve innervated muscles.

Conclusion

Thus a wide variety of myopathies are encountered in India and as the diagnostic facilities become more easily available, further useful information will come to light.

References

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19. Gourie Devi M, Choudhury JR, Vasanth A et al. Correlation of clinical profile of myotonic dystrophy with CTG repeats in the myotonin protein kinase gene. Indian J Med Res 1998;107:187-96.

20. Basu P, Gangopadhaya PK, Mukherjee SC et al. Molecular anatomy of myotonin protein kinase gene among myotonic dystrophy patients from east India. Hum Mutat 2000;369:1-7.

21. Deepti AN, Gayathri N, Veerendra Kumar M, Shankar Susarla K. Nemaline myopathy: A report of four cases. Ann Ind Acad Neurol 2007;10:175-7.

22. Challa S, Kanikannan MA, Jagarlapudi MM, Bhoompally VR, Surath M. Diagnosis of mitochondrial diseases: Clinical and histological study of sixty patients with ragged red fibers. Neurol India 2004;52:353-8.

23. Irani PF. Electromyography in nutritional osteomalacic myopathy. J Neurol Neurosurg Psychiatry 1976;39:686-93.

24. Prasad ML, Sarkar C, Roy S et al. Idiopathic inflammatory myopathy: clinicopathological observations in the Indian population. Br J Rheumatol 1992;31:835-39.

25. Narayanaswamy AS, Akhtar M, Kumar N et al. Polymyositis: a review and follow-up of 24 cases. J Assoc Physicians India 1993; 41:354-56.

26. Thassu A, Prabhakar S, Bansal SK et al. Polymyositis: a clinical profile. Neurol India 1993;41:93-97.

27. Gayatri N, Vasanth A, Veerendra Kumar M et al. Inclusion body myositis. Clin Neuropathol 2000;19:13-20.