Atchayaram Nalini (India)
NIMHANS Department of NeurologyAuthor Of 1 Presentation
NOVEL MUTATION OF EXOSC3 PRESENTING AS HEREDITARY SPASTIC PARAPLEGIA PLUS SYNDROME.
- Dipti Baskar (India)
Abstract
Background and Aims:
RNA processing protein 40 (RRP40) is an exosome complex involved in processing RNA, of which EXOSC3 forms a non-catalytic subunit. Homozygous mutation in EXOSC3 causes Pontocerebellar hypoplasia-1 (PCH-1), characterised by postnatal psychomotor retardation with spinal motor neuron degeneration. Imaging in PCH-1 shows severe cerebellar and variable pontine atrophy. Here we report an adolescent male with EXOSC3 mutation who presented with spastic paraparesis and nystagmus since childhood with severe vermian atrophy and normal pons suggestive phenotypically Hereditary spastic paraplegia plus syndrome (HSP-Plus).
Methods:
A 19 years old male born of non-consanguinous parentage presented with symptoms of unsteadiness while walking along with slurring of speech since three years of age. Examination showed a high arched palate, low set ears, elbow joint contracture, gaze-evoked nystagmus, spastic dysarthria, upper limb power 3/5, and spasticity of lower limbs with power 4/5 and bilateral extensor plantar.
Results:
The visually evoked potential was prolonged bilaterally. MRI brain showed severe atrophy of vermis with moderate atrophy cerebellar hemispheres without pontine atrophy (Figure). Clinical exome sequencing revealed a homozygous mutation in exon 3 of EXOC3 (variant- c.571G>A).
Conclusions:
This report reveals the variable phenotypic spectrum of EXOSC3 mutation and its analysis to be considered in patients with early-onset spastic paraparesis and nystagmus with cerebellar atrophy in the absence of pontine atrophy and other classical features.