Refining Domain-Based Prognostication in DNM1 Encephalopathy: A Mild Phenotype Associated With a GTPase Domain Variant.
Caroline Crain, Hope Northrup, Laura S Farach et al.
✦ AI-curated · Sources linked
Case in brief
A female patient presented with well-controlled epilepsy and mild dysmorphic features, without the developmental impairment commonly described in DNM1 encephalopathy. Trio exome sequencing identified a de novo likely pathogenic variant in the GTPase domain of DNM1, supporting the diagnosis. Her attenuated presentation contrasts with the severe phenotype typically associated with the condition and with prior milder cases that included developmental impairment. The report highlights that the clinical spectrum may be broader than previously recognized and that the patient’s course challenges confident prognostication based on variant domain alone.
What made this case unusual
The patient had a GTPase-domain variant—historically associated with more severe disease—yet presented with well-controlled epilepsy and mild dysmorphic features without reported developmental impairment.
Diagnostic / clinical pearl
A DNM1 GTPase-domain variant does not necessarily predict a severe phenotype; interpret domain-based prognostication cautiously in light of clinical variability.