Objective: To examine  genotype-phenotype correlations in a cohort of three patients with Perrys syndrome. 

Background: Perrys syndrome is a rare cause of familial parkinsonism. Since the identification of Dynactin 1 with ten pathogenic mutations in Perry’s syndrome,there has been an expansion of the clinical spectrum, including progressive supranuclear palsy like presentation, frontal behavioural syndromes and variable levodopa responsiveness.

Methods: A review of the clinical features and genetic mutations was undertaken in three unrelated subjects.

Results: A 66 year old female presented with severe depression and weight loss for 2 years followed by gait problems and urinary urgency. Her brother died within a few years of the onset of Parkinsonism in his sixties. Examination revealed symmetrical Parkinsonism and frontal cognitive deficits. She had no central hypoventilation. She had heterozygous mutations for DCTN1 c.202A>G(p.Lys68Glu). She had an excellent response to levodopa, but developed impulsivity and motor fluctuations within 12 months.

A 56 year old female presented with weight loss, tremors and cognitive problems. Multiple family members had developed Parkinsonian syndromes (age range 46-54 years), dying within 3 years of symptom onset. Examination revealed symmetrical Parkinsonism and frontal cognitive deficits. She later developed dysphagia requiring a PEG tube and central apnoeic episodes. She was heterozygous for DCTN1c.202A>G (p.Lys68Glu). She had no response to levodopa and died 4 years from onset.

A 46 year old man presented with difficulty concentrating. He was under psychiatry for 10 years with anxiety and resistant depression. He had prominent frontal release signs, abnormal saccadic eye movements and executive dysfunction. 2 years later, he developed Parkinsonism with partial levodopa response.He later required nocturnal ventilation for respiratory failure. Heterozygous mutation DCTN1 c.200G>A(p. Gly67Asp) was detected. He died 15 years after onset.

Conclusions: Given the expanding clinical spectrum,DCTN1 mutations should be considered in the differential diagnosis of all cases of atypical Parkinsonian syndromes with a strong family history. Based on other reported cases and this case series, there is no evidence to suggest a strong phenotype-genotype correlation. Whilst there is no cure, early detection of the syndrome may prompt early respiratory support, which could improve quality of life.   

References: 1. Chung EJ, Hwang JH, Lee MJ, Hong JH, Ji KH, Yoo WK, Kim SJ, Song HK, Lee CS, Lee MS, Kim YJ. Expansion of the clinicopathological and mutational spectrum of Perry syndrome. Parkinsonism Relat Disord. 2014;20:388–93.

2. Araki E, Tsuboi Y, Daechsel J, Milnerwood A, Vilarino-Guell C, Fujii N, Mishima T, Oka T, Hara H, Fukae J, Farrer MJ. A novel DCTN1 mutation with late-onset parkinsonism and frontotemporal atrophy. Mov Disord. 2014;29:1201–4.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/are-there-genotype-phenotype-correlations-in-perrys-syndrome/