A 9-year-old girl presented with mild motor delay and progressive proximal limb-girdle weakness. Socio-cognitive milestones were normally attained. Examination revealed normal head size and intellectual functioning, proximal limb girdle weakness, mildly prominent calves, and preserved deep tendon jerks (including both ankles). She had hyperlaxity of finger joints and both elbow joints (Beighton score 4/9). She also had polyminimyoclonus. Creatine kinase levels were elevated (790 IU/L) while electrocardiogram revealed tremor (Fig. 1). Nerve conduction studies revealed motor axonal loss with sensory sparing while electromyography (EMG) was suggestive of abnormal spontaneous activity (fibrillations and fasciculations) signifying active denervation. She was not cooperative for voluntary EMG assessment. Multiplex ligation-dependent probe amplification (MLPA) revealed homozygous deletion of exon 7 and 8 of SMN1 gene confirming the diagnosis of spinal muscular atrophy type 3 (SMA type 3).

Fig. 1 Electrocardiogram of the index patient showing the high frequency (30-40 Hz) tremor (arrows) due to muscle fasciculations (seen predominantly in limb leads).

Important differential diagnosis for progressive limb girdle weakness presenting in late childhood (with onset beyond infancy) include muscular dystrophies (especially Duchenne muscular dystrophy and limb girdle muscular dystrophies) and SMA type 3. It may be difficult to differentiate these conditions based on deep tendon jerks and creatine kinase levels because these are often misleading. Deep tendon reflexes may be preserved in SMA type 3 [1]. Joint hypermobility and hyperlaxity, although an overlooked feature of SMA, if present favors a diagnosis of SMA over muscular dystrophy [2,3]. The caveats include early-onset muscle disorders such as congenital muscular dystrophies and congenital myopathies [2]. In SMA, anterior horn cell loss begins in early infancy and may possibly account for distal hypotonia and hyperlaxity. Hyperlaxity, especially of upper limb joints may persist till adulthood in more than half of patients [4]. It is perplexing to see that this finding was not captured in major prospective cohorts of SMA type 2 and 3, which predominantly addressed the weakness and ambulation. This finding needs to be further confirmed in large cohorts not only because of diagnostic significance but also for rehabilitation point of view, considering the improved outcomes with newer therapies in SMA.

1. Lannaccone ST, Browne RH, Samaha FJ, Buncher CR.　Prospective study of spinal muscular atrophy before age 6 years. Pediatr Neurol. 1993;9: 187-93.

2. Donkervoort S, Bonnemann CG, Loeys B, Jungbluth H, Voermans NC. The neuromuscular differential diagnosis of joint hypermobility. Am J Med Genet C Semin Med Genet. 2015;169C:23-42.

3. Haaker G, Fujak A. Proximal spinal muscular atrophy: Current orthopedic perspective. Appl Clin Genet. 2013;6:113-20.

4. Tofts LJ, Elliott EJ, Munns C, Pacey V, Sillence DO. The differential diagnosis of children with joint hypermobility: A review of the literature. Pediatr Rheumatol Online J. 2009;7:1.