Adult‐Onset Neurodegeneration in Nucleotide Excision Repair Disorders (<scp>NERD<sub>ND</sub></scp>): Time to Move Beyond the Skin

Cordts, Isabell; Önder, Demet; Traschütz, Andreas; Kobeleva, Xenia; Karin, Ivan; Minnerop, Martina; Köertvelyessy, Pèter; Biskup, Saskia; Forchhammer, Stephan; Binder, Johannes; Tzschach, Andreas; Meiß, Frank; Schmidt, Axel; Kreiß, Martina; Cremer, Kirsten; Mensah, Martin A.; Park, Joo Hyun; Rautenberg, Maren; Deininger, Natalie; Sturm, Marc; Lingor, Paul; Klopstock, Thomas; Weiler, Markus; Marxreiter, Franz; Synofzik, Matthis; Posch, Christian; Sirokay, Judith; Klockgether, Thomas; Haack, Tobias B.; Deschauer, Marcus

doi:10.1002/mds.29071

Cited by 12 publications

(6 citation statements)

References 45 publications

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“…Similar to published literature, the MRI of the brain suggested diffuse cerebral atrophy in our case [ 15 ]. Our case exhibited decreased interaction with his family members which could be attributed to apathy due to the atrophy of the bilateral frontal cortices (especially the left median frontal cortex) and the anterior cingulate gyri [ 16 ].…”

Section: Discussionsupporting

confidence: 90%

“…In a case report by Garcia-Moreno et al, XP-G was associated with a Huntington-like phenotype with mild apathy at the onset and overt neuropsychiatric manifestations developed later in the disease course [ 14 ]. Furthermore, prominent psychiatric manifestations at the onset have not been previously described among the 13 patients with adult-onset neurodegeneration due to mutations in the NER system [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

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Adult-Onset Neuropsychiatric Symptoms as the Presenting Feature of Xeroderma Pigmentosum Group G: A Report of a Rare Case

Saluja,

Kaur,

Anees

et al. 2024

Cureus

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Xeroderma pigmentosum is a rare autosomal recessive disorder resulting in heightened cutaneous photosensitivity due to aberrant DNA repair mechanisms. Early-life developmental delay and cognitive impairment have been described in xeroderma pigmentosum cases. However, psychiatric symptoms in adulthood as the presenting feature of xeroderma pigmentosum have not been reported. We report a young adult with xeroderma pigmentosum group G presenting with prominent neuropsychiatric manifestations and evidence of neurodegeneration. The clinical, laboratory, and radiological findings, skin biopsy, and the results of the genetic testing of the patient have been described after obtaining written and informed consent. A young adult male with skin photosensitivity since infancy developed hyper-religiosity, delusions, suicidal ideations, speech hypernasality, lower limb spasticity, and cognitive impairment over the past four years. The MRI of the brain showed diffuse cerebral atrophy. The skin biopsy from bilateral cheeks showed evidence of flattening and thinning of rete ridges, pigment incontinence, and perivascular and periappendageal inflammatory infiltrate. The whole exome sequencing in ethylenediaminetetraacetic acid (EDTA) blood revealed a compound heterozygous likely pathogenic mutation in intron 13 (c.2880-2A>G (3' splice site)) and a mutation in exon 15 (c.3146del (p.Asp1049ValfsTer12)) in the ERCC5 gene suggestive of xeroderma pigmentosum group G. This case highlights that prominent neuropsychiatric features in adulthood can occur due to xeroderma pigmentosum. Thus, xeroderma pigmentosum group G should be considered as a possibility among young adults presenting with neuropsychiatric features, evidence of neurodegeneration, and early-life skin photosensitivity.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Adult-Onset Neuropsychiatric Symptoms as the Presenting Feature of Xeroderma Pigmentosum Group G: A Report of a Rare Case

Saluja,

Kaur,

Anees

et al. 2024

Cureus

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“…It is worth noting that new genetic techniques are allowing the early diagnosis and phenotypic expansion of several diseases, especially in cases with unusual characteristics and/or milder phenotypes as observed in the CS III subject. Some reports described diagnoses of CS III with initial isolated developmental delay or ataxicdystonic signs or mild isolated ataxia followed by neurodegeneration in adulthood [12][13][14][15][16][17]. The abovementioned data seem to indicate that the ERCC6-related CS represents a spectrum ranging from very severe to milder forms in which the clinical characterization remains important from a diagnostic (i.e., easier clinical recognition of severe form vs. more difficult clinical recognition of milder forms) and prognostic point of view, since earlier CS II forms appear to have the most severe involvement and the worse outcome, while the outcome for milder CS III forms remains unclear, given the limited number of reported patients and poor long-term follow-up data.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms

Sartorelli,

Travaglini,

Macchiaiolo

et al. 2024

Genes

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(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a clear genotype-phenotype correlation for both the two causative genes ERCC6 (CS type B) and ERCC8 (CS type A). We assessed this, presenting a series of patients with genetically confirmed CSB. (2) Materials and Methods: We retrospectively collected demographic, clinical, genetic, neuroimaging, and serum neurofilament light-chain (sNFL) data about CSB patients; diagnostic and severity scores were also determined. (3) Results: Data of eight ERCC6/CSB patients are presented. Four patients had CS I, three patients CS II, and one patient CS III. Various degrees of ataxia and spasticity were cardinal neurologic features, with variably combined systemic characteristics. Mean age at diagnosis was lower in the type II form, in which classic CS signs were more evident. Interestingly, sNFL determination appeared to reflect clinical classification. Two novel premature stop codon and one novel missense variants were identified. All CS I subjects harbored the p.Arg735Ter variant; the milder CS III subject carried the p.Leu764Ser missense change. (4) Conclusion: Our work confirms clinical variability also in the ERCC6/CSB type, where manifestations may range from severe involvement with prenatal or neonatal onset to normal psychomotor development followed by progressive ataxia. We propose, for the first time in CS, sNFL as a useful peripheral biomarker, with increased levels compared to currently available reference values and with the potential ability to reflect disease severity.

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“…Cockayne syndrome (CS) is a multisystem dysfunction with growth failure, progressive demyelinating neuropathy, gait problems, and characteristic postnatal physical features. 1,2 This autosomal recessive disorder is divided into two subtypes; 20% of patients are Cockayne syndrome-A (CSA) related to ERCC8 variants, and 80% of patients are Cockayne syndrome-B (CSB), characterized by ERCC6 variants. 3 Herein, a CS patient carrying homozygous variants in ERCC6 with a short stature, and neck and hand tremor has been described.…”

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confidence: 99%

A Case of ERCC6‐Related Cockayne Syndrome Presenting with Levodopa‐Responsive Tremor Syndrome

Salari,

Rezaei,

Asadi

et al. 2023

Movement Disord Clin Pract

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Adult‐Onset Neurodegeneration in Nucleotide Excision Repair Disorders (NERD_ND): Time to Move Beyond the Skin

Cited by 12 publications

References 45 publications

Adult-Onset Neuropsychiatric Symptoms as the Presenting Feature of Xeroderma Pigmentosum Group G: A Report of a Rare Case

Adult-Onset Neuropsychiatric Symptoms as the Presenting Feature of Xeroderma Pigmentosum Group G: A Report of a Rare Case

Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms

A Case of ERCC6‐Related Cockayne Syndrome Presenting with Levodopa‐Responsive Tremor Syndrome

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Adult‐Onset Neurodegeneration in Nucleotide Excision Repair Disorders (NERDND): Time to Move Beyond the Skin

Cited by 12 publications

References 45 publications

Adult-Onset Neuropsychiatric Symptoms as the Presenting Feature of Xeroderma Pigmentosum Group G: A Report of a Rare Case

Adult-Onset Neuropsychiatric Symptoms as the Presenting Feature of Xeroderma Pigmentosum Group G: A Report of a Rare Case

Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms

A Case of ERCC6‐Related Cockayne Syndrome Presenting with Levodopa‐Responsive Tremor Syndrome

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Adult‐Onset Neurodegeneration in Nucleotide Excision Repair Disorders (NERD_ND): Time to Move Beyond the Skin