DNM1Lpathogenic variants lead to mitochondrial fission dysfunction. According to the latest publication in Jan 2025, 97 unrelated probands (AD de novo and 1 homozygous), 3 couples of siblings (AR) and 1 couple of half-siblings (AD) have been reported for 44 different DNM1Lpathogenic variants. The median age of onset (or first evaluation) was 24 months (birth – 11 years). Lethality was 27%, 29.5% and 20% for patients carrying a pathogenic variant in the GTPase, middle and GED domains, respectively. The total lethality was 28% (death occurring between 8 day – 17 year of life). Prevalence is very rare, less than 1:1,000,000.
Main clinical features include encephalopathy, cardiomyopathy, neurodevelopmental disorder, epilepsy, neuropathy, movement disorder. Plasma very long chain fatty acids(C26) are mostly normal. Some patients present with lactic acidosis, and/or respiratory chain deficiencies in muscle and/or skin fibroblasts. Most patient's fibroblasts disclose abnormally elongated mitochondria and some show abnormal peroxisome morphology.