Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient | CS Type | Age (Years) | Sex | Age at Diagnosis (Years) | Pathogenic Variants | Genetic Classification |
---|---|---|---|---|---|---|
1 | CS I | 17 | F | 17 | ERCC6: homozygous c.2203C>T; p.Arg735Ter | CSB |
2 | CS I | 7 | F | 3 | ERCC6: c.2203C>T, p.Arg735Ter; 10q11.22-q11.23 microdeletion | CSB |
3 | CS I | 16 | M | 4.5 | ERCC6: c. 2203C>T, p.Arg735Ter; c.2096_2097insC, p.Leu700ValfsTer60 | CSB |
4 | CS I | 21 | M | 5 | ERCC6: c.2751C>T, p.Gly917Gly paternally inherited; c.2203C>T, p.Arg735Ter paternally inherited; chromosome 10 5.5Mb deletion maternally inherited | CSB |
5 | CS II | 2.5 | M | 1 | ERCC6: c.2784_2785delAG, p.Arg 928fsTer5; c.1881C>A, p.Tyr627Ter | CSB |
6 | CS II | 5 | F | 1 | ERCC6: homozygous c.1431_1432delGA, p.K478TfsTer9 | CSB |
7 | CS II | 3 | M | 1 | ERCC6: c.2383-1G>T, splice acceptor variant; c.3259C>T, p.Arg1087Ter | CSB |
8 | CS III | 9 | M | 9 | ERCC6: c.2096dupC, p.Leu700fsTer60; c.2291T>C, p.Leu764Ser | CSB |
Patient CS Type | Ophtalmologic | Gestation and Birth | Photosensitivity | Growth Failure | Dysphagia | Hypertransaminasemia | Other Features | Diagnostic Score: CS; CRS | Severity Score |
---|---|---|---|---|---|---|---|---|---|
1 CS I | Normal vision | Normal | Yes | Yes, <−5 SD | No | Yes (at age 1 y), then normalized | - | 9/20; 19/39 | 5/15 |
2 CS I | Small opacity in left eye lens; reduced retinic pigmentation (salt and pepper appearance) | Reduced head circumference growth during gestation | Yes | Yes, −2 SD | Yes | Yes (at age 4 y), then normalized | - | 8/20; 16/39 | 8/15 |
3 CS I | Astigmatism | CSec at 37 GW due to fetal bradycardia | Yes | Yes, <−5 SD | Yes | Yes | Photophobia. Cryptorchdism. | 7/20; 13/39 | 4/15 |
4 CS I | Hypermetropy | Normal | Yes | Yes, <−5 SD | Yes | Yes | Scoliosis. Cryptorchidism. | 7/20; N/A | 3/15 |
5 CS II | Normal vision | Reduced growth during last month | Yes | Yes, <−5 SD | No | Yes | Enophtalmia. | 10/20; N/A | 2/15 |
6 CS II | Bilateral congenital cataract, with recurrence after surgical treatment | CSec at 36 GW due to growth restriction; SGA at birth | Yes | Yes, <−5 SD | Yes | Yes | - | 10/20; 16/39 | 1/15 |
7 CS II | Hypermetropy | Right clubfoot and bilateral pyelectasis | No | Yes, <−5 SD | Yes | Yes | Thoracic kiphosis. Cryptorchidism. Enophtalmia. | 8/20; 13/39 | 2/15 |
8 CS III | Normal vision | Normal | No | No | No | No | Monolateral kidney dysplasia. | 0/20; 3/39 | 14/15 |
Pat. | CS Type | Spasticity | Ataxia | Seizures | Microcephaly | Maximum Developmental Milestone (Age) | Language Development | sNFL (pg/mL) | Brain MRI Findings | Neurophisiologic Findings |
---|---|---|---|---|---|---|---|---|---|---|
1 | CS I | Yes | Yes | No | Yes, −4 SD | Walk (2 y, lost 3 y) | Poor | 45 | Age: 4 y and 9 y: Progressive cerebral and cerebellar atrophy; thin CC; permanent hypomyelination | ERG: normal; VEP: increased latency; BAEP: increased I–V latency; SSEP: increased CCT |
2 | CS I | Yes | Yes | No | Yes, −3 SD | Walk with support (2 y) | Poor | 99–136 | Age: 10 m and 1.5 y: Progressive cerebral and cerebellar atrophy; thin CC; WM reduction and hypomyelination | NCV: normal |
3 | CS I | Yes | Yes | No | Yes, <−5 SD | Walk with support (1.7 y) | Poor | N/A | Age: 4 y: Permanent hypomyelination | ERG: reduced amplitude |
4 | CS I | Yes | No | No | Yes, <−5 SD | Walk (1 y), then regression | Poor | N/A | N/A | N/A |
5 | CS II | Yes | No | No | Yes, <−5 SD | Head control (4.5 m) | Poor | 175 | N/A | N/A |
6 | CS II | Yes | Yes | Yes | Yes, <−5 SD | No acquisition | No acquisition | N/A | Age: 5 m: Cerebral, cerebellar, CC, and WM reductions; reduced myelination for age | EEG: occipital anomalies; VEP: poor cortical definition; BAEP: increased I–V latency |
7 | CS II | Yes | Yes | No | Yes, <−5 SD | Head control (5 m) | Poor, then regression | 198–270 | Age 7 m: Cerebral, cerebellar, CC, and WM reductions; reduced myelination for age | NCV: demyelinating SM neuropathy; ERG: normal; VEP: high latency |
8 | CS III | No | Yes | No | No | Walk (1 y) | Normal | 49 | Age: 8 y: mild posterior WM T2 hyperintensity; increased posterior fossa | BAEPs: increased I–V latency; ERG/VEP: normal; NCS: mild decrease in motor conduction velocity in the lower limbs |
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Sartorelli, J.; Travaglini, L.; Macchiaiolo, M.; Garone, G.; Gonfiantini, M.V.; Vecchio, D.; Sinibaldi, L.; Frascarelli, F.; Ceccatelli, V.; Petrillo, S.; et al. Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms. Genes 2024, 15, 508. https://doi.org/10.3390/genes15040508
Sartorelli J, Travaglini L, Macchiaiolo M, Garone G, Gonfiantini MV, Vecchio D, Sinibaldi L, Frascarelli F, Ceccatelli V, Petrillo S, et al. Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms. Genes. 2024; 15(4):508. https://doi.org/10.3390/genes15040508
Chicago/Turabian StyleSartorelli, Jacopo, Lorena Travaglini, Marina Macchiaiolo, Giacomo Garone, Michaela Veronika Gonfiantini, Davide Vecchio, Lorenzo Sinibaldi, Flaminia Frascarelli, Viola Ceccatelli, Sara Petrillo, and et al. 2024. "Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms" Genes 15, no. 4: 508. https://doi.org/10.3390/genes15040508