Claudin-11-Mediated Hypomyelinating Leukodystrophy 22: New Insights Into Pathogenic Mechanisms.
Fabio Acquaviva, Serena Troisi, Gabriella Errichiello et al.
✦ AI-curated · Sources linked
Case in brief
A child presented with global developmental delay, hypotonia, limb hypertonia, esotropia, and absence of early milestones, later showing partial motor improvement but persistent cognitive impairment. Brain MRI indicated diffuse supratentorial hypomyelination. Genetic testing revealed a novel homozygous CLDN11 start-loss variant, indicating an autosomal recessive mechanism, contrasting with previously reported dominant variants.
What made this case unusual
The case highlights a novel homozygous CLDN11 variant, expanding the genetic spectrum of hypomyelinating leukodystrophy and suggesting distinct pathogenic mechanisms compared to previously reported cases.
Diagnostic / clinical pearl
Clinicians should consider CLDN11-related hypomyelinating leukodystrophy in patients with developmental delays and hypomyelination, especially when typical dominant variants are ruled out.
Why it matters
This case emphasizes the importance of genetic testing in understanding the diverse mechanisms underlying leukodystrophies, which can inform diagnosis and genetic counseling.