Case details:

We report a sibling pair who presented with mixed upper and lower motor neuron signs with a rare mitochondrial fusion protein disorder.

Case 1: An 18 month old boy child, born at full-term after an uneventful delivery, presented with motor delay and hypotonia. At 3 months of age he was investigated for an apnoeic and floppy episode. At that time MRI brain and spine was normal. On examination at 18 months he had lower limb muscle atrophy, hypotonia and brisk reflexes. Electrophysiology revealed axonal neuropathy and the repeat MRI showed periventricular hyperintensities. Genetic studies revealed a heterozygous missense variant in exon 18 of the MFN-2 gene.

Case 2: His older half-sister now 10 years of age initially was hypotonic in infancy and later developed spasticity and atrophy with brisk reflexes. Electrophysiology showed severe sensory motor axonal neuropathy. Brain MRI showed periventricular hyperintensities. She has also got the same mutation as her brother.

 Discussion:

Mitofusin-2 (MFN-2) is a protein required for mitochondrial fusion that in humans is coded by the MFN-2 gene. Mutations in MFN-2 are mainly responsible for Charcot Marie Tooth disease type 2A.

Conclusion:

Our cases are not only rare but also had unusual presentation of MFN-2 mutation. They demonstrated spasticity with brisk reflexes clinically but had severe neuropathy on electrophysiology. We recommend that MFN-2 mutation testing should be considered in any child presenting with unexplained neurological examination with contradictory neurophysiological results and periventricular hyperintensities.