Spectrum of Pediatric to Early Adulthood POLR3A-Associated Movement Disorders

Alonso Zea Vera; Adrienne Bruce; Travis R Larsh; Zachary Jordan; Norbert Brüggemann; Ana Westenberger; Alberto J Espay; Donald L Gilbert; Steve W Wu

doi:10.1002/mdc3.13635

Spectrum of Pediatric to Early Adulthood POLR3A-Associated Movement Disorders

Mov Disord Clin Pract. 2022 Dec 23;10(2):316-322. doi: 10.1002/mdc3.13635. eCollection 2023 Feb.

Authors

Alonso Zea Vera^{1

2}, Adrienne Bruce^{3

4}, Travis R Larsh^{5

6}, Zachary Jordan⁷, Norbert Brüggemann^{8

9}, Ana Westenberger⁸, Alberto J Espay⁷, Donald L Gilbert^{5

6}, Steve W Wu^{5

6}

Affiliations

¹ Department of Neurology Children's National Hospital Washington DC USA.
² Department of Neurology George Washington University School of Medicine & Health Sciences Washington DC USA.
³ Department of Pediatrics Prisma Health Greenville South Carolina USA.
⁴ University of South Carolina School of Medicine Greenville Greenville South Carolina USA.
⁵ Division of Neurology Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA.
⁶ Department of Pediatrics University of Cincinnati College of Medicine Cincinnati Ohio USA.
⁷ Department of Neurology University of Cincinnati Gardner Neuroscience Institute Cincinnati Ohio USA.
⁸ Institute of Neurogenetics University of Lübeck Lübeck Germany.
⁹ Department of Neurology University of Lübeck Lübeck Germany.

Abstract

Background: POLR3A pathogenic variants are associated with hypomyelination, hypodontia, hypogonadism, and movement disorders.

Cases: We describe the range of movement disorders seen in six patients (four female, two male) with POLR3A variants [three novel (c.2214del, c.3775G>A, c.3905G>T) and six previously reported (c.760C>T, c.1771-7C>G, c.1909+22G>A, c.2005C>T, c.2422C>T, c.3337-11T>C)]. Patient 1 presented with a neonatal progeroid syndrome and developed parkinsonism, dystonia, ataxia, and spasticity. Patient 2 presented with infant-onset rapidly progressive chorea, and dystonia. Three patients (patients 3, 5, 6) presented predominantly with ataxia in combination with spasticity and dystonia. Patient 4 developed segmental dystonia during adolescence and ataxia in early adulthood. Four patients had vertical gaze impairment. The most common brain MRI abnormality was T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain.

Conclusion: POLR3A-related disorders exhibit significant phenotypic pleomorphism. Vertical gaze dysfunction and T2-weighted/FLAIR hyperintensity of the superior cerebellar peduncles and midbrain may be useful signs suggestive of this condition.

Keywords: POLR3A; ataxia; dystonia; rare diseases; vertical gaze palsy.

Publication types

Case Reports