Focus area: Physicians
Sleep disordered breathing and GH replacement in patients affected by PWS
Prader Willi syndrome (PWS) is characterized by several respiratory issues characterizing the evolution of the pathology. Sleep disordered breathing are one of the major comorbidities; their assessment is crucial to start and to continue GH (Growth Hormone) therapy.
Prader Willi syndrome (PWS) is a multisystem genetic disorder characterized by the lack of expression of genes represented on chromosome 15q11-q13. Obstructive apneas, central apneas and nocturnal hypoventilation are present in PWS patients. In this syndrome, an abnormal response to hypoxia and to hypercapnia has been demonstrated. Obstructive apnea is related to: obesity, hypotonia, micrognathia, small nose and oropharynx, viscous secretions. The lack of Necdin (NDN), one of a cluster of genes deleted in PWS, involved in the correct axonal development, determine an abnormal respiratory rythmogenesis causing central apneas. Central apneas are prevalent during REM sleep. Hypotonia, obesity and scoliosis are factors contributing to the determination of nocturnal hypoventilation.
GH (Growth Hormone) has been shown to be an effective drug in patients affected by PWS. However, there was considerable concern surrounding its safety following several reports of sudden death in PWS patients shortly after GH initiation. The development or worsening of obstructive sleep apnea has been reported in children who have started GH therapy. Conversely, the central hypoventilation has been demonstrated to improve with GH treatment for direct effects of the drug on the hypothalamic function. Therefore, the drug can be administered safely, in severe obese patients or untreated severe OSA. A sleep study should be performed prior to starting GH and OSA should be identified and eventually treated. A repeat sleep study should be performed 3-6 months following initiation of GH therapy and patients should continue to be monitored for signs and symptoms of OSA thereafter.
Ref: Tan HL, Urquhart DS.Respiratory Complications in Children with Prader Willi Syndrome. Paediatr Respir Rev. 2017 Mar;22:52-59.