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Salih myopathy is an autosomal recessive early-onset myopathy with fatal cardiomyopathy characterized by global hypotonia, delayed motor milestones, and progressive dilated cardiomyopathy. In a 2-year-old proband requiring continuous mechanical ventilation, genetic testing revealed compound heterozygosity for two TTN variants: c.56572C>T (p.Arg18858Ter) and c.15218-2A>G (PMID:38482259). Motor delay (HP:0001270) was an early manifestation alongside rapidly deteriorating cardiac function.
The identification of a single proband with truncating and splice-site TTN variants supports a loss-of-function mechanism in this titinopathy. However, in the absence of segregation analyses or functional studies, the current evidence remains limited. TTN sequencing should be considered in infants presenting with congenital hypotonia and early cardiomyopathy to guide diagnosis and management. Key take-home: biallelic truncating or splice TTN mutations underlie severe Salih myopathy, warranting early genetic testing for diagnostic and therapeutic decision-making.
Gene–Disease AssociationLimitedOne unrelated proband with compound heterozygous TTN variants and characteristic phenotype Genetic EvidenceLimitedOne proband with compound heterozygous truncating and splice site variants; no segregation data Functional EvidenceNoneNo functional or experimental studies reported |