ADPRHL2 is involved in posttranslational modification and is known to have a role in physiological functions such as cell signaling, DNA repair, gene control, cell death, and response to stress. Recently, a group of neurological disorders due to ADPRHL2 variants is described, characterized by childhood-onset, stress-induced variable movement disorders, neuropathy, seizures, and neurodegenerative course. We present the diagnostic pathway of two pediatric patients with episodic dystonia and ataxia, who later had a neurodegenerative course complicated by central hypoventilation syndrome due to the same homozygous ADPRHL2 variant. We conducted a systematic literature search and data extraction procedure following the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 statement in terms of patients with ADPRHL2 variants, from 2018 up to 3 February, 2023. In total, 12 articles describing 47 patients were included in the final analysis. Median age at symptom onset was 2 (0.7–25) years, with the most common presenting symptoms being gait problems (n = 19, 40.4%), seizures (n = 16, 34%), ataxia (n = 13, 27.6%), and weakness (n = 10, 21.2%). Triggering factors (28/47; 59.5%) and regression (28/43; 60.4%), axonal polyneuropathy (9/23; 39.1%), and cerebral and cerebellar atrophy with white matter changes (28/36; 77.7%) were the other clues. The fatality rate and median age of death were 44.6% (n = 21) and 7 (2–34) years, respectively. ADPRHL2 variants should be considered in the context of episodic, stress-induced pediatric and adult-onset movement disorders and seizures.

1. Research project: A. Conception, B. Organization, and C. Execution.

2. Statistical analysis: A. Design, B. Execution, and C. Review and critique.

3. Manuscript preparation: A. Writing of the first draft and B. Review and Critique.

S.Ö.Y.: 1A, 2A, 2B, 3A; D.Y.: 3B; P.Ö.Ş.K.: 1A, 3B; R.G.: 3B; M.S.: 3B; G.E.U.: 3B; and G.H.: 1A, 1B, 1C, 2C, 3B.

The authors confirm that the approval of an institutional review board was not required for this work. Written and verbal consent from the parents were obtained for this study, including case presentations and video images. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

None.

Informed consent was obtained.

Received: 27 September 2023

Accepted: 29 December 2023

Article published online:
16 February 2024

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