King-Denborough Syndrome Caused by a Novel Mutation in the Ryanodine Receptor Gene

Malignant hyperthermia (MH) is a rare pharmacogenetic syndrome characterized by muscle rigidity, respiratory and metabolic acidosis, and an elevation in body temperature after exposure to inhalational anesthetics. MH has been associated with a number of myopathies, including central core disease (CCD) and King-Denborough syndrome.1 King-Denborough syndrome is defined by a tendency to anesthetic-induced MH in children with proximal weakness and characteristic dysmorphic features.2 Mutations in the skeletal muscle calcium release channel ryanodine receptor ( RYR1 ) gene cause MH and CCD.1 We describe a girl with phenotypic features of King-Denborough syndrome and confirmed susceptibility to MH, in whom sequencing revealed a novel heterozygous A97G point mutation in exon 2 of RYR1. ### Case report. The patient was born at term after a pregnancy complicated by decreased fetal movements and breech presentation. Hypotonia and dysmorphism (bilateral ptosis, limited vertical gaze, a high-arched palate, prominent philtrum, and scaphocephaly) were noted at birth. She had early failure to thrive. Neurologic examination showed hypotonia with mild facial and proximal limb weakness and normal deep tendon reflexes. The father and paternal grandfather had congenital ptosis without other signs of neuromuscular disease. The mother and siblings were clinically unaffected. Electromyography (EMG) and serum …