Dataset Information

Spectrum of Pediatric to Early Adulthood POLR3A-Associated Movement Disorders.

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.

SUBMITTER: Zea Vera A

PROVIDER: S-EPMC9941928 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Spectrum of Pediatric to Early Adulthood <i>POLR3A</i>-Associated Movement Disorders.

Zea Vera Alonso A Bruce Adrienne A Larsh Travis R TR Jordan Zachary Z Brüggemann Norbert N Westenberger Ana A Espay Alberto J AJ Gilbert Donald L DL Wu Steve W SW

Movement disorders clinical practice 20221223 2

<h4>Background</h4><i>POLR3A</i> pathogenic variants are associated with hypomyelination, hypodontia, hypogonadism, and movement disorders.<h4>Cases</h4>We describe the range of movement disorders seen in six patients (four female, two male) with <i>POLR3A</i> 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 parkinsoni ...[more]

PMID: 36825045

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