Search

Chronic progressive external ophthalmoplegia (CPEO) is symptom complex with progressive ptosis and restricted ocular motility without diplopia. MYH2myopathy is rare disorder presenting with CPEO and muscle weakness. We report two Indian patients of MYH2myopathy with unique features. Patient-1 presented with early adult-onset esophageal reflux followed by, proximal lower limb weakness, proptosis, CPEO without ptosis. He had elevated creatine kinase along with characteristic muscle MRI findings of prominent semitendinosus and medial gastrocnemius involvement. Patient -2 presented with early adult onset CPEO without limb weakness. His creatine kinase was normal. Both the patients had novel MYH2mutations: a homozygous 5’splice variation in intron 4 (c.348?+?2dup) in patient 1 and homozygous single base pair deletion in exon 32 (p. Ala1480ProfsTer11) in patient 2. Unique features noted include adult onset, isolated CPEO, proptosis, esophageal reflux disease and absence of skeletal abnormalities. MYH2myopathy has to be considered in adult patients with CPEO.

Mitochondrial Calcium Uptake 1 (MICU1) is an important component of mitochondrial calcium channel regulator. Mutations in MICU1result in a rare syndrome of myopathy with extrapyramidal features. Here we report a rare case of MICU1related myopathy from India. A 23 years old male presented with 10 years history of proximal muscle weakness with exertional myalgia and fatigue. Examination showed facial dysmorphism with facial weakness and mildly reduced visual acuity. Limb girdle pattern of weakness with hypoactive tendon reflexes were noted without extrapyramidal signs. He had elevated serum creatine level of 1542 IU/L. Muscle MRI had novel findings of selective fatty infiltration of hamstrings, medial gastrocnemius and soleus. Muscle biopsy showed myopathic with secondary neurogenic changes along with few COX deficient fibres. Genetic analysis showed compound heterozygous pathogenic variants in MICU1gene at intron 9 (c.1072-1 G > C) – splice site variant and exon 5 (c.513T > A) – stop gained variant, both resulting in loss of function of the protein. The variants were segregating in unaffected parents in heterozygous state with variant c.1072-1 G > C in the unaffected father and variant c.513T > A (p. Tyr171*) in the unaffected mother confirming the diagnosis. This report highlights the phenotype of limb girdle weakness with facial dysmorphism and optic atrophy expanding the spectrum of MICU1 related syndrome with novel MRI muscle and histopathological findings.