Neurology India Medknow Publications on behalf of the Neurological Society of India ISSN: 0028-3886 EISSN: 1998-4022 Vol. 51, Num. 3, 2003, pp. 417-418

Neurology India, Vol. 51, No. 3, July, 2003, pp. 417-418

Merosin negative congenital muscular dystrophy: A short report

Ralte AM, Sharma MC, Gulati S, Das M, Sarkar C
Departments of Pathology, All India Institute of Medical Sciences, Ansarinagar, New Delhi - 110029

Correspondence Address:
Department of Pathology, All India Institute of Medical Sciences, Ansarinagar, New Delhi - 110029
sarkarcs@hotmail.com

Code Number: ni03140

ABSTRACT

We report a rare case of an infant with congenital muscular dystrophy who presented at birth with marked generalized hypotonia and normal mental development. Creatinine phosphokinase (CPK) level was markedly raised; however no white matter abnormalities were detected by brain imaging techniques. Immunohistochemical staining for merosin (laminin alpha 2) was negative, thereby confirming merosin-deficient congenital muscular dystrophy.

INTRODUCTION

Congenital muscular dystrophy comprises a group of muscle diseases consisting of the Fukuyama type, Walker Warburg syndrome, muscle eye brain disease and classical congenital muscular dystrophy. The latter is classified into laminin alpha 2 positive and laminin alpha 2 negative subtypes. The merosin negative subtype comprises about 30% of congenital muscular dystrophies (CMDs).[1] We report a rare case of histologically proven congenital muscular dystrophy (CMD). To the best of our knowledge such a case has not been documented earlier in Indian literature.

CASE REPORT

A 4-month-old female child, born of non-consanguineous marriage, presented with history of decreased limb movements and low-pitched cry since birth. She had poor suck reflex resulting in poor feeding, which required nasogastric supplements. There was intercostal muscle weakness; however, respiratory distress was not evident. Examination revealed generalized gross hypotonia with reduced bulk of muscles. There were no fasciculations and deep tendon reflexes were not elicitable. Social smile was present at 3 months of age indicating normal mental development. There were no joint deformities or contractures. Creatinine phosphokinase (CPK) level was 2451 U/L and electromyogram was suggestive of a myopathic disorder. Brain imaging revealed no abnormality. Muscle biopsy showed a dystrophic pattern with marked endomysial and perimysial fibrosis and infiltration by adipose tissue [Figure-1a] & [Figure-1b]. No regenerating or degenerating fibers or myophagocytosis was seen. Immunohistochemistry for muscle membrane proteins dystrophin 1,2 and 3 showed a normal staining pattern [Figure-2a], [Figure-2b] & [Figure-2c]. The antibody used for the immunolabeling of merosin was lyophilized monoclonal antibody (clone mer 3/22 B2-Novocastra Labs) to the 300 KD fragment, at a dilution of 1:50. The absence of staining for merosin confirmed the diagnosis of merosin negative congenital muscular dystrophy.

DISCUSSION

CMDs comprise a heterogenous group of autosomal recessive disorders of infancy.[2] They were first described by Batten[3] in 1903 but it was Howard[4] who referred to this disease as 'dystrophia muscularis congenita'. The reports of different clinicopathological phenotypes and the recent progresses in immunocytochemistry and molecular genetics allowed the precise identification of specific entities within the group of CMDs. The two more common forms are the merosin deficient CMD which accounts for about 30% of classical CMDs, and the Fukuyama CMD which is associated with major brain abnormalities and is almost exclusively observed in Japan. Other well-individualized forms are the muscle eye brain disease, almost exclusively reported in Finland, and the Walker-Warburg syndrome which is also a rare disease but spread worldwide.

Merosin, also called laminin alpha 2 is a component of the extracellular muscle membrane linked to alpha dystroglycan whose genetic locus is on chromosome 6q2.[5] The laminins influence adhesion, differentiation, growth, shape and migration of cells. Laminin alpha 2 plays a role in myogenesis, promoting myotube stability by preventing apoptosis.[6] Mutations of the laminin alpha 2 gene induce the formation of abnormal laminins, which disturb the assembly and stability of the laminin network resulting in the typical clinicopathological phenotype. This can be demonstrated by immunohistochemical studies using a monoclonal antibody that reacts with either the C terminal 80 kDa polypeptide or the 300 kDa fragment.[7]

Patients with merosin negative CMD present with severe neonatal hypoxia often requiring ventilatory assistance, markedly delayed motor development and generalized muscle atrophy with weakness of limb and trunk muscles leading to contractures and joint deformities. In contrast with other CMD patients, those with merosin deficiency have high creatinine phosphokinase levels[1] and white matter abnormalities are detected by brain imaging techniques.

The electromyogram is generally considered myogenic as was seen in this case but slow motor conduction velocities have been found in a series of cases.[8]Although there is a considerable variability from case to case, the histologic changes observed in the skeletal muscle are similar to those seen in the muscular dystrophies that occur at an older age like marked variation in the size of muscle fibers, absent or few necrotic and regenerating fibers and marked increase in endomysial connective tissue along with clinical features which help in making this diagnosis. This is further substantiated by merosin negativity in muscle fibers.

The evolution of this disease is often severe mainly due to respiratory insufficiency; the motor functions in most cases do not deteriorate significantly after the first years of life. Prenatal diagnosis can be made by immunocytochemical studies of chorionic villous samples and genetic linkage analysis. [9]

Remarkable progress has been made towards the elucidation of the molecular etiology underlying this disease using animal models.[10],[11] This has made an impact on the diagnosis and understanding of the disease, to provide better patient care management and to offer, hopefully in the not too distant future, significant therapeutic perspectives.

REFERENCES

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