{
  "abstract": "Cockayne Syndrome (CS) is a rare autosomal recessive neuro-progressive disorder caused by pathogenic variants in DNA repair genes (e.g ERCC6 and ERCC8). Since 2019, the National Service for Cockayne Syndrome/Trichothiodystrophy has enabled comprehensive clinical and molecular profiling of over 70 patients. Late-onset cases of CS are uncommon and often misdiagnosed.Here we report six patients with genetically confirmed ERCC6-related CS with a normal clinical course during the first two decades of life, followed by neurocognitive decline and hemiplegic migraine. Symptoms onset ranged from age 16 to the mid-30s, with diagnosis established between ages 20 and 59. Initial presentations included hemiplegic migraine (n=3) without variants in known familial hemiplegic migraine genes, early neurocognitive decline (n=3), and tremor, speech, and balance difficulties (n=3). MRI findings were consistent across all patients, showing diffuse leukoencephalopathy, basal ganglia calcifications, and cerebral and cerebellar atrophy.All patients were compound heterozygotes for the splice donor site variant c.2286+5G>A in ERCC6. We hypothesise that this variant results in aberrant splicing and deletion of exon 11 from the ERCC6/CSB mRNA and that a residual amount of normal splicing produces enough ERCC6/CSB protein to delay symptoms onset. We are currently testing this hypothesis.These findings expand the late-onset CS phenotype.",
  "authors": [
    {
      "affiliations": [
        "National Cockayne and Trichothiodsytrophy (CS/TTD) Service, Rare Diseases Centre and Clinical Genetics Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Arwa Babai"
    },
    {
      "affiliations": [
        "National Cockayne and Trichothiodsytrophy (CS/TTD) Service, Rare Diseases Centre and Clinical Genetics Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Shehla Mohammed"
    },
    {
      "affiliations": [
        "National Cockayne and Trichothiodsytrophy (CS/TTD) Service, Rare Diseases Centre and Clinical Genetics Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Hiva Fassihi"
    },
    {
      "affiliations": [
        "National Cockayne and Trichothiodsytrophy (CS/TTD) Service, Rare Diseases Centre and Clinical Genetics Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Phillipa Sellar"
    },
    {
      "affiliations": [
        "National Cockayne and Trichothiodsytrophy (CS/TTD) Service, Rare Diseases Centre and Clinical Genetics Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Paula Sullivan"
    },
    {
      "affiliations": [
        "National Cockayne and Trichothiodsytrophy (CS/TTD) Service, Rare Diseases Centre and Clinical Genetics Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Adesoji Abiona"
    },
    {
      "affiliations": [
        "Department of Clinical Genetics, St George’s University Hospitals NHS Foundation Trust, South West Thames Centre for Genomics, London, UK"
      ],
      "name": "Nayana Lahiri"
    },
    {
      "affiliations": [
        "Nottingham Clinical Genetics Department, The Gables, Nottingham City Hospital, Nottingham, UK"
      ],
      "name": "Abhijit Dixit"
    },
    {
      "affiliations": [
        "Nottingham Clinical Genetics Department, The Gables, Nottingham City Hospital, Nottingham, UK"
      ],
      "name": "Nora Shannon"
    },
    {
      "affiliations": [
        "National Cockayne and Trichothiodsytrophy (CS/TTD) Service, Rare Diseases Centre and Clinical Genetics Department, Guy’s and St Thomas’ NHS Foundation Trust, London, UK"
      ],
      "name": "Paola Giunti"
    },
    {
      "affiliations": [
        "Genome Damage and Stability Centre, University of Sussex, Brighton, UK"
      ],
      "name": "Alan Lehmann"
    }
  ],
  "title": "P10 Unique insights from a national multidisciplinary rare disease service: expanding the phenotype of late-onset ERCC6-related cockayne syndrome with hemiplegic migraine as a novel clinical feature",
  "uid": "cb24c32a-2500-533a-8042-ec66e48d74dd"
}