A clinical and genetic study of spinal muscular atrophy.
OBJECTIVE
This study evaluates clinical, electromyography (EMG) and genetic analysis of consecutive patients with spinal muscular atrophy (SMA) in a tertiary care adult neurology practice in India.


METHODS
Consecutive patients with SMA attending the neurology out patient department during 2001-2003 were included. They were subjected to a detailed clinical examination, nerve conduction and EMG and muscle biopsy. Clinically patients were classified into generalised and segmental SMA. SMN gene deletion study was carried out in all the patients.


RESULTS
There were 15 patients with type III and type IV SMA and 15 with segmental SMA (Hirayama disease). The age ranged between 5 and 23 years in type III SMA, 33-50 years in type IV SMA and 16-30 years in Hirayama disease (HD). The latter was found exclusively in males. Family history was observed in 1 patient each in all the groups. In SMA III mother and brother were affected, in SMA IV two siblings and in HD one brother had similar disease. One type III SMA family was associated with deafness and one type IV family had strong association with maturity onset diabetes in young. The EMG was characterised by lack of fibrillations in all type III and IV SMA patients except 1 whereas in HD, 11 out of 15 had fibrillations suggesting ongoing denervation. The EMG was suggestive of reinnervation in generalised SMA in both upper and lower limb muscles where as these abnormalities were restricted to C7-T1 mytomes in HD. Muscle biopsy in 10 patients with generalised SMA revealed group atrophy in all, and loss of fascicular architecture in 3, clumping of nuclei in 7 and hypertrophic fibers in 4. SMN1 gene deletion was present in 3 patients with type III but none in type IV and HD.


CONCLUSIONS
SMN gene deletion was positive in 33% type III SMA whereas it was negative in type IV and HD. Presence of HD only in males may be consistent with X-linked disorder.
Mishra
V N
VN
Department of Neurology, Sanjay Gandhi PGIMS, Lucknow. ukmisra@sgpgi.ac.in
Kalita
J
J
Kesari
A
A
Mitta
B
B
Shankar
S K
SK
Misra
U K
UK
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D017362:Cyclic AMP Response Element-Binding Protein; D004576:Electromyography; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009431:Neural Conduction / Q000502:physiology; D010375:Pedigree; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; D014897:Spinal Muscular Atrophies of Childhood / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D013127:Spinal Nerves / Q000503:physiopathology; D055533:Survival of Motor Neuron 1 Protein
D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein