(CR 15) MORC2 Neurodevelopmental Disorder - a Mitochondrial Disease Masquerader

Introduction:

MORC2 gene mutations cause a newly described neurodevelopmental disorder with growth retardation and variable craniofacial dysmorphism. We present a case report of a patient with a heterozygous MORC2 mutation who was initially diagnosed with Leigh syndrome based on clinical presentation and typical MRI brain findings. The aim of this case report is to highlight the possibility of other genetic conditions masquerading as a mitochondrial disorder.

Case Report/Description :

A 2-year-old boy with a background of global development delay and hypotonia presented with hemiplegia, dystonia and neuroregression following a minor fall. Physical examination revealed left upper motor neuron facial nerve palsy, left hemiplegia, generalized hypotonia and hyporeflexia. His serum and cerebrospinal fluid lactate levels were increased. MRI brain showed bilateral symmetrical T2 hyperintensities in the basal ganglia and brainstem.  Leigh full panel and SURF1 gene analysis by Sanger sequencing did not detect any causative mutation. Whole exome sequencing identified a heterozygous likely pathogenic variant in the MORC2 gene: c.79G>A (p. Glu27Lys) which is consistent with his clinical phenotype.

 Discussion/Conclusion :

Microrchidia CW- zinc finger type 2 (MORC2) encodes for an ATPase fundamental for epigenetic silencing by the human silencing hub (HUSH) complex, which is expressed in neural tissues. As it binds to ATP             citrate lyase which catalyses formation of acetyl Co-A, this is the potential mechanism for mitochondrial-like disease features. In view of the wide differential diagnosis for abnormalities of the basal ganglia, it is important to pursue a molecular diagnosis and be open to expanding clinical spectrums for newly described disorders.