How common are ear, nose and throat disorders in children with Noonan syndrome and other RASopathies?

INTRODUCTION: Noonan syndrome and related conditions (RASopathies) are known to be associated with abnormalities in many organ systems. It is our impression that few otolaryngologists are familiar with the manifestations of these syndromes and we therefore reviewed our hospital's patient cohort to identify the prevalence of ear, nose and throat disorders in these children. METHODS: We cross-referenced various hospital department databases (otolaryngology, audiology, cardiology, haematology and genetics) to try to identify as many children with Noonan and other RASopathies as possible. We then performed a retrospective review of electronic patient records. RESULTS: We identified 67 children with Noonan, Costello, LEOPARD and other RASopathy syndromes. Around half have been seen in otolaryngology and audiology clinics. Otitis media with effusion requiring ventilation tubes occurred in 4% of children. 10% have suffered recurrent acute otitis media. 9% have a sensorineural hearing loss. 7% have undergone adenotonsillectomy for obstructive sleep apnoea. Airway anomalies and head and neck malformations occur but are rare. DISCUSSION: Children with Noonan and other RASopathies present commonly to otolaryngology and audiology clinics. The prevalence of sensorineural hearing loss is high and audiological screening is likely to be worthwhile. Surgeons should be aware that complications of surgery are common and can be very severe, especially in those with cardiac anomalies.

Troponin T is essential for sarcomere assembly in zebrafish skeletal muscle.

In striated muscle, the basic contractile unit is the sarcomere, which comprises myosin-rich thick filaments intercalated with thin filaments made of actin, tropomyosin and troponin. Troponin is required to regulate Ca(2+)-dependent contraction, and mutant forms of troponins are associated with muscle diseases. We have disrupted several genes simultaneously in zebrafish embryos and have followed the progression of muscle degeneration in the absence of troponin. Complete loss of troponin T activity leads to loss of sarcomere structure, in part owing to the destructive nature of deregulated actin-myosin activity. When troponin T and myosin activity are simultaneously disrupted, immature sarcomeres are rescued. However, tropomyosin fails to localise to sarcomeres, and intercalating thin filaments are missing from electron microscopic cross-sections, indicating that loss of troponin T affects thin filament composition. If troponin activity is only partially disrupted, myofibrils are formed but eventually disintegrate owing to deregulated actin-myosin activity. We conclude that the troponin complex has at least two distinct activities: regulation of actin-myosin activity and, independently, a role in the proper assembly of thin filaments. Our results also indicate that sarcomere assembly can occur in the absence of normal thin filaments.