King-Denborough syndrome: a clinicogenetic case report

Abstract

King–Denborough syndrome is a rare RYR1-related congenital myopathy characterized by dysmorphic features, muscle weakness, and susceptibility to malignant hyperthermia, often posing a diagnostic challenge in early infancy. We report a one-year-old female child presenting with developmental delay and generalized hypotonia. Clinical evaluation revealed craniofacial dysmorphism, bilateral ptosis, and esotropia, raising suspicion of an underlying congenital myopathy. Initial laboratory and imaging workup were inconclusive except for transient elevation of creatine kinase. Whole exome sequencing identified a heterozygous missense variant in the RYR1 gene (c.14126C>T; p.Thr4709Met), along with a likely pathogenic FOXP1 variant. In view of the characteristic clinical phenotype, a diagnosis of King–Denborough syndrome was considered. The child was managed with supportive therapy and developmental interventions, and caregivers were counselled regarding the risk of malignant hyperthermia. This case underscores the importance of clinicogenetic correlation in diagnosing rare myopathies and highlights the need for early recognition to enable appropriate counselling and prevention of anaesthetic complications.