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Background: Variants in dehydrodolichol diphosphate synthetase (DHDDS) and nuclear undecaprenyl pyrophosphate synthase 1 (NUS1) cause a neurodevelopmental disorder, classically with prominent epilepsy. Recent reports suggest a complex movement disorder and an overlapping phenotype has been postulated due to their combined role in dolichol synthesis. Cases: We describe three patients with heterozygous variants in DHDDS and five with variants affecting NUS1. They bear a remarkably similar phenotype of a movement disorder dominated by multifocal myoclonus. Diagnostic clues include myoclonus exacerbated by action and facial involvement, and slowly progressive or stable, gait ataxia with disproportionately impaired tandem gait. Myoclonus is confirmed with neurophysiology, including EMG of facial muscles. Literature Review: Ninety‐eight reports of heterozygous variants in DHDDS, NUS1 and chromosome 6q22.1 structural alterations spanning NUS1, confirm the convergent phenotype of hypotonia at birth, developmental delay, multifocal myoclonus, ataxia, dystonia and later parkinsonism with or without generalized epilepsy. Other features include periodic exacerbations, stereotypies, anxiety, and dysmorphisms. Although their gene products contribute to dolichol biosynthesis, a key step in N‐glycosylation, transferrin isoform profiles are typically normal. Imaging is normal or non‐specific. Conclusions: Recognition of their shared phenotype may expedite diagnosis through chromosomal microarray and by including DHDDS/NUS1 in movement disorder gene panels. [ABSTRACT FROM AUTHOR]

1) revealing diffuse leukodystrophy, basal ganglia and cerebellar atrophy, along with a thin corpus callosum, suggestive of hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome), a syndrome first described in 2002. Serial detailed phenotyping allowed recognition of childhood-onset, progressive, combined, dystonia as our patients gradually developed the typical disease milestones of dystonia, cerebellar signs and whispering dysphonia. Keywords: H-ABC syndrome; TUBB4A; TUBB4A-related disease; whispering dysphonia EN H-ABC syndrome TUBB4A TUBB4A-related disease whispering dysphonia S54 S57 4 08/28/23 20230802 NES 230802 We describe two sisters in whom careful characterization of movement disorder phenomenology and recognition of evolving biomarkers were key diagnostic factors after 30 years of follow-up. [Extracted from the article]

Neuronal intranuclear inclusion disease (NIID) is the pathological hallmark of a heterogeneous neurodegenerative disease spanning dementia, neuropathy, parkinsonism, encephalitic episodes, and seizures.[1] Onset may be in infancy, childhood, or adulthood and be sporadic or familial. "Biopsy-positive" I NOTCH2NLC i -ET with normal imaging, however, may later progress to the characteristic DWI change of NIID.[10] I NOTCH2NLC- i NIID with typical imaging findings may present as stable adult-onset CD. NOTCH2NLC GGC Repeat Expansion Presenting as Adult-Onset Cervical Dystonia. [Extracted from the article]

Isolated Craniocervical Dystonia Without Initial Neuropsychiatric Manifestations Associated with NMDA-Receptor Antibodies We describe a patient presenting with isolated craniocervical dystonia and serum and cerebrospinal fluid (CSF) NMDAR antibody positivity, without other manifestations of encephalitis at presentation. Keywords: NMDA; craniocervical dystonia; autoimmune encephalitis EN NMDA craniocervical dystonia autoimmune encephalitis 680 682 3 04/18/23 20230401 NES 230401 N-methyl-D-aspartate receptor (NMDAR) encephalitis classically manifests as varying combinations of neuropsychiatric disturbance, autonomic dysfunction, hypoventilation, and salient movement disorders. [Extracted from the article]

Background: Variants in EIF2AK2 have been recently associated with a spectrum of neurological disease encompassing isolated dystonia to fever‐related neurological decompensation, movement disorders and leukodystrophy. Case: A 32‐year old patient presented with childhood‐onset episodes of neurological decompensation after febrile illness, progressive anarthria, dystonia and spasticity. The T2/FLAIR MRI showed bilateral posterolateral putamen hyperintensities and white matter changes suggestive of leukodystrophy. Initial extensive metabolic workup and whole genome sequencing (WGS) was unremarkable. Re‐analysis of the WGS data revealed a variant in exon 3 of the EIF2AK2 gene [(NM_001135651.3): c.92C > G (p.Pro31Arg)]. EIF2AK2‐associated disorders should be incorporated into the differential diagnosis of the syndrome of fever‐related neurological decompensation with movement disorders, especially in the presence of abnormal neuroimaging. Literature review: Disease‐causing variants in EIF2AK2 have been reported in 24 individuals from 16 families in the literature to date. Two broad phenotypes have been described, including: (1) childhood‐onset generalized dystonia and a normal brain MRI; and (2) early childhood‐onset developmental delay combined with movement disorders, spasticity, and seizures in some. Notably, 92% of these patients have neurological deterioration after febrile illness or other physiological stress. Hypomyelination or delayed myelination and thin corpus callosum are seen in most patients and lower medullary lessions are common. Basal ganglia lesions have been reported previously in one case. Conclusions: EIF2AK2‐associated disorders should be incorporated into the differential diagnosis of the syndrome of fever‐related neurological decompensation with movement disorders, especially in the presence of abnormal neuroimaging. [ABSTRACT FROM AUTHOR]

Background: Variants in EIF2AK2 have been recently associated with a spectrum of neurological disease encompassing isolated dystonia to fever-related neurological decompensation, movement disorders and leukodystrophy., Case: A 32-year old patient presented with childhood-onset episodes of neurological decompensation after febrile illness, progressive anarthria, dystonia and spasticity. The T2/FLAIR MRI showed bilateral posterolateral putamen hyperintensities and white matter changes suggestive of leukodystrophy. Initial extensive metabolic workup and whole genome sequencing (WGS) was unremarkable. Re-analysis of the WGS data revealed a variant in exon 3 of the EIF2AK2 gene [ (NM_001135651.3): c.92C > G (p.Pro31Arg)]. EIF2AK2 -associated disorders should be incorporated into the differential diagnosis of the syndrome of fever-related neurological decompensation with movement disorders, especially in the presence of abnormal neuroimaging., Literature Review: Disease-causing variants in EIF2AK2 have been reported in 24 individuals from 16 families in the literature to date. Two broad phenotypes have been described, including: (1) childhood-onset generalized dystonia and a normal brain MRI; and (2) early childhood-onset developmental delay combined with movement disorders, spasticity, and seizures in some. Notably, 92% of these patients have neurological deterioration after febrile illness or other physiological stress. Hypomyelination or delayed myelination and thin corpus callosum are seen in most patients and lower medullary lessions are common. Basal ganglia lesions have been reported previously in one case., Conclusions: EIF2AK2 -associated disorders should be incorporated into the differential diagnosis of the syndrome of fever-related neurological decompensation with movement disorders, especially in the presence of abnormal neuroimaging., Competing Interests: The authors report no specific grants for this research financial disclosure. No conflicts of interest are reported by the authors., (© 2021 International Parkinson and Movement Disorder Society.)