The core clinical picture of RMND1-related disorders is characterized by hypotonia, developmental delay and sensorineural deafness. Beside the rare congenital form, the most severe phenotype so far described is the infantile form. This entails the presence of global developmental delay, hypotonia, myopathy and early childhood death due to end stage renal failure.
Brain imaging is characterized by diffuse brain white matter abnormalities suggestive of hypomyelination. Biochemical analysis often shows increase lactate in serum (~60% of patients). Muscle biopsy reveals COX negative and ragged-red fibers, as well as decreased activity of multiple respiratory enzyme activities (complex I, III and IV). Interestingly, in RMND1-related disorders, renal failure has been reported in up to 60% of the patients and it is due to tubular acidosis type 4 or cystic/hypoplastic kidneys (in contrast with other mitochondrial nephropathies characterized by proximal tubulopathy or glomerulopathy). Cardiopathy and failure to thrive are also frequent.
It is worth mentioning that severity of RMND1-related disorder varies. Although most of the patients have limited survival, with death within the first 3 years of age, there are individual who have been diagnosed at age 40 and even a subject diagnosed at 61 years of age, with ovarian insufficiency and sensory neural hearing loss (Perrault syndrome), and chronic renal failure.
RMND1