Three New Families With Perry Syndrome From Distinct Parts Of The World- Novel Mutation And Successful Treatment Attempt Of Respiratory Insufficiency (P3.086)

OBJECTIVE: Perry syndrome is a rapidly progressive autosomal dominant disorder with Parkinsonism, depression, weight loss, and central hypoventilation. BACKGROUND: So far five mutations in 11 families have been observed: G71R, G71E, G71A, T72P, and Q74P located in exon 2 of the dynactin 1 ( DCTN1 ) gene on chromosome 2p13.1. In functional assays, all of them altered microtubule binding. DESIGN/METHODS: Genealogical, clinical, genetic, and functional studies were performed on three families from Colombia, New Zealand, and the USA. A diaphragmatic pacemaker was implanted in the Colombian family proband to treat her respiratory insufficiency. Dopaminergic therapy was initiated in the majority of the patients. RESULTS: In addition to three available probands, 14 symptomatic relatives from the three families were identified. The cardinal signs of Perry syndrome were present in all three probands with symptomatic disease onset in their sixth decade of life. Parkinsonian signs were mild to moderate with a poor response to dopaminergic treatment. All affected family relatives including the probands from the New Zealand and US families died of respiratory insufficiency. In the Colombian and US families the G71R mutation was identified, whereas in the New Zealand family a novel Y78C mutation was discovered, which also altered microtubule binding. The proband from the Colombian family is alive most likely due to early diagnosis and implantation of a diaphragmatic pacemaker. Follow-up examinations over the period of two years have revealed good function of the diaphragmatic pacemaker without any major complications. The patient has displayed a high grade of independence in her everyday life. CONCLUSIONS: Perry syndrome is a rare condition, but new cases will likely continue to emerge worldwide. Early diagnosis may prevent life-threatening acute respiratory failure. Diaphragmatic pacemakers should be considered as a safe and effective symptomatic treatment option. Parkinsonian features, although always present, may not be disabling. Study Supported by: NINDS P50NS072187, and NS078086, Mayo Clinic Center for Individualized Medicine, Gerstner Family Career Development Award, and Max Kade Foundation. Disclosure: Dr. Tacik has nothing to disclose. Dr. Fujioka has nothing to disclose. Dr. Ross has nothing to disclose. Dr. Springer has nothing to disclose. Dr. Fiesel has nothing to disclose. Dr. Pretelt has nothing to disclose. Dr. Castaneda Cardona has nothing to disclose. Dr. Kidd has nothing to disclose. Dr. Hlavac has nothing to disclose. Dr. Raizis has nothing to disclose. Dr. Okun has received royalty payments from Demos, Humana, Amazon and Cambridge. Dr. Okun has received research support from the Michael J. Fox Foundation, the National Parkinson Foundation, the Parkinson Alliance, the Smallwood Foundation, the Tourette Syndrome Association, the Bachmann-Strauss Foundation, and the National Institutes of Health. Dr. Wszolek has received personal compensation in an editorial capacity for Parkinsonism and Related Disorders, and for the European Journal of Neurology. Dr. Wszolek has received license fee payments from Mayo Clinic. Dr. Wright has received research support from the National Institutes of Health, Mayo Clinic Florida, and the Dystonia Medical Research Foundation.