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Fatal infantile hypertonic myofibrillar myopathy (FIHMM) is an autosomal recessive disorder marked by early-onset muscle amyotrophy, progressive hypertonia, apnea, respiratory failure, and elevated creatine kinase. Approximately 18 affected individuals harboring CRYAB mutations have been reported worldwide ([PMID:36727013]). A 2-year-old Chinese female presented in infancy with restrictive ventilatory dysfunction, acute respiratory distress, pneumothorax, and cardiac arrest leading to fatal respiratory failure. Genetic analysis identified compound heterozygous CRYAB variants: c.302A>C (p.His101Pro) and c.3G>A (p.Met1Ile), each inherited from an asymptomatic parent ([PMID:36727013]). Muscle biopsy showed myofibrillar disintegration with accumulation of desmin, αB-crystallin, and myotilin, and electron microscopy revealed dense intramyofibrillar granules. These findings implicate loss of αB-crystallin chaperone function in FIHMM pathogenesis. CRYAB should be included in diagnostic panels for early-onset myofibrillar myopathies to confirm the diagnosis and inform genetic counseling.
Gene–Disease AssociationLimitedSingle published family; compound heterozygous CRYAB variants in one proband; ~18 cases reported worldwide Genetic EvidenceLimitedBiallelic missense variants identified in a single proband with no extended segregation Functional EvidenceLimitedMuscle biopsy and electron microscopy demonstrate αB-crystallin aggregation and dense granules consistent with myofibrillar myopathy |