Cosegregation of congenital dysferlinopathy phenotype and marinesco–sjögren syndrome: a case report with literature review

The congenital dysferlinopathy phenotype is the rarest and earliest manifestation variant, described in two closely related Spanish and Turkish families, with a homozygous pathogenic frameshift variant in exon 26 of the DYSF gene. This article presents a 1.6-year-old patient from a consanguineous Uzbek family with a clinical diagnosis of congenital dysferlinopathy phenotype and Marinesco–Sjögren syndrome with transient postnatal hypotonia, motor development delay, muscle weakness in the flexors of the neck and proximal limbs, convergent strabismus, cerebellar truncal ataxia, minimal intention tremor of the upper limbs, a slight increase in the levels of creatinine phosphokinase (CK) to 353 U/L (2.4×N) and that of myoglobin to 40 µg/mL (2×N). Magnetic resonance imaging (MRI) revealed pronounced edematous changes in the gastrocnemius muscle on short tau inversion recovery (STIR). MRI signs of minimal fat replacement and hypotrophy were noted in the medial and posterior thigh and gastrocnemius muscles. MRI of the head revealed hypoplasia of the vermis and cerebellar hemispheres. Whole-exome sequencing revealed compound heterozygous DYSF variants: NM_001130987.2:c.1000 C > T (p.(Arg334Trp)) and NM_001130987.2:c.518 C > T (p.(Thr173Met)), and a previously described homozygous SIL1 variant NM_022464.5:c.178G > T (p.(Glu60Ter)). Histopathological examination revealed minimal signs of myopathy and dysferlin in only 1% of the muscle fibers. At the ultrastructural level, signs of dysferlinopathy and Marinesco–Sjögren syndrome were detected. This clinical case is an example of the cosegregation of two diseases that mutually potentiate damage to skeletal muscles.