ICNC Abstracts, ICNC 2018

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Next generation sequencing: a magic bullet or a cautious sword?
Shruti Bajaj, Mamta Muranjan, Anaita Hegde, Mukesh Agrawal

Last modified: 2018-09-09


Introduction: Next-generation-sequencing (NGS) is guiding the diagnosis in many neurological disorders where multiple differentials exist due to phenotypic overlap.

Diagnosis inapparent

a) 4-year female presented with developmental delay and idiopathic infantile-spasms. Investigations revealed normal neuroimaging, metabolic work-up and abnormal EEG. NGS-panel for infantile spasms was unyielding. Reflexive NGS-testing of all candidate neurological genes diagnosed Neurodegeneration-with-brain-iron-accumulation-type5 (WDR45 gene).

b) 18-month female presented with acute encephalopathy, developmental delay, antenatal-onset microcephaly, growth-retardation, craniofacial dysmorphisms and lissencephaly-pachygyria complex with partial corpus-callosum-dysgenesis. Two older siblings with similar phenotype expired at 4-months and day-2. WES-trio diagnosed proband as Microcephalic-Osteodysplastic-Primordial-Dwarfism-type1 (RNU4ATAC gene).

Diagnosis apparent

c) 8-years male presented with delayed motor milestones, waddling gait. Examination revealed hypotonia, head drop, proximal muscle weakness in the limbs, absent lower-limb reflexes, elbow and ankle contractures, calf muscles’ wasting and positive Gower’s sign. EMG suggested generalised myopathy. CPK was elevated. Clinical-exome revealed autosomal-dominant Emery-Dreifuss-muscular-dystrophy (LMNA gene), as suspected clinically.

d) 4.5-year female presented with floppiness, delayed motor milestones and recurrent shoulder dislocations. Examination revealed hypermobile joints, skin hyperlaxity, fleshy scars, blue sclera, microcornea, global hypotonia, preserved power, normal reflexes. EMG, NCV tested normal. The constellation of floppiness, elevated CPK and abnormal musculoskeletal-MRI, prompted a suspicion of congenital myopathic spectrum, elsewhere. Muscle biopsy and myopathic-panel were planned, but deferred. Connective-tissue-disorder was suspected. Clinical-exome yielded diagnosis of Ehler-Danlos-VI (PLOD1 gene).

Conclusion: Common neurological presentations have wide range of clinical differentials, caused by different genes. NGS can yield results if applied after careful clinical correlation.


Next generation sequencing;Neurogenentics;Infantile spasms; Muscular Dystrophy; Microcephaly; Hypotonia

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