King-Denborough syndrome, do we know the mechanism?

Abstract

King-Denborough syndrome (KDS) is a rare condition characterized by dysmorphic features like Noonan syndrome and malignant hyperthermia susceptibility. The exact mechanism for this condition is not clear. Noonan syndrome is caused by mutations in genes in the RAS-MAPK pathway. Our 4-year-old male patient is one of three male siblings born to non-consanguineous couple with birth weight of 2.5 kg. He had bilateral ptosis and developed malignant hyperthermia while having anesthesia before surgery for ptosis. On examination, he has ptosis, low-set ears, webbed neck, pectus excavatum. His head circumference is just above 50th percentile, height and weight between 10th and 25th percentile. He does not have clinical evidence of heart disease and has a normal neurological examination. The father of our patient has been operated for scoliosis, but did not have facial features of Noonan syndrome. Our patient has a mutation in the RYR1 gene c.7523G>A p. Arg2508His. His mother or siblings do not have this mutation. He has been advised about the risk of anesthesia and is being monitored for his growth and development. Although there is overlap between Noonan syndrome and KDS, no definite mechanism has been reported in causation of KDS. Although we do not have any proven explanation for the presence of Noonan like features in KDS, we postulate that the RYR1 gene in combination with some other genetic modifier may be affecting the RAS-MAPK pathway. It is also possible that the similarity between KDS and Noonan syndrome is just a coincidence.