Phenotypic Delineation of Combined Oxidative Phosphorylation Deficiency-12: Clinical Features of 2 Patients

Combined oxidative phosphorylation deficiency-12 (COXPD12) is a rare autosomal recessive disorder. Neurological findings and lactic acidosis can be presenting signs of COXPD12.

Here, we present identical dysmorphic facial features that have not been described before in the literature, in 2 patients with two different EARS2 gene variants. Case 1 was a 2.5-month-old male who presented with hypotonia and lactic acidosis. Cranial magnetic resonance imaging (MRI) showed diffusion restriction in the supratentorial deep white matter, around the ventricle, in the bilateral periaqueductal gray matter at the level of the basal ganglia, and in the dentate nuclei in the tegmentum. Case 2 was a 2-month-old boy who also presented with lactic acidosis and hypotonia. Diffusion MRI reported hypomyelination. Dysmorphic facial features including slight metopic ridge, ptosis, wide palpebral fissure length, sparse eyebrows, bulbous nose, thin upper lip, full cheeks, small chin, large ears, thin ear helix, and prominent antihelix were common findings in both patients. Molecular genetic analysis indicated c.319C>T(p. Arg107Cys) common genetic variant in our 2 patients. In case 2, the second allele was a novel genetic variant.

For COXPD12 disease, facial features are considered the main diagnostic clue, such as hypotonia or lactic acidosis; thus, the characteristic facial phenotype will help clinicians diagnose the disease.