Novel Homozygous Mitochondrial Calcium Uptake Protein 1 Variant (c.38T>C, p.Leu13Pro) in a 7-year-old Girl with Congenital Ptosis and Proximal Myopathy: Expanding the Phenotypic Spectrum.
Poornima Lakshmi, Shiji Chalipat, Manasseh Kunchepu et al.
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Case in brief
A 7-year-old Indian girl presented with global developmental delay, congenital nonfatigable right ptosis, and proximal-predominant myopathy without calf hypertrophy. Examination also showed multiple dysmorphic features, and brain MRI demonstrated a thickened corpus callosum. Creatine kinase was 4068–4732 U/L; electromyography showed a myogenic pattern, with normal nerve conduction and nondecremental repetitive nerve stimulation. Whole-exome sequencing identified a homozygous MICU1 c.38T>C (p.Leu13Pro) missense variant, classified as a variant of uncertain significance. The findings were reported as a case of MICU1-related myopathy.
What made this case unusual
The reported combination included congenital ptosis, absent calf hypertrophy, and a thickened corpus callosum—features the authors identified as atypical for pediatric MICU1-related myopathy. The associated homozygous variant was novel but classified as a variant of uncertain significance.
Diagnostic / clinical pearl
In a child with developmental delay and proximal myopathy, congenital ptosis and a thickened corpus callosum may accompany a suspected MICU1-related disorder, even without calf hypertrophy. Interpret the genetic finding in light of its uncertain-significance classification.