Cockayne Syndrome 

  • Author: Suguru Imaeda, MD; Chief Editor: Dirk M Elston, MD   more...
 
Updated: Jan 25, 2012
 

Background

Cockayne syndrome[1] is a rare autosomal recessive, heterogeneous, multisystem disorder characterized by dwarfism, progressive pigmentary retinopathy, birdlike facies, and photosensitivity. The syndrome is divided into 2 subtypes. Cockayne syndrome I, or classic Cockayne syndrome, presents in childhood with characteristic facies and somatic features that occur late in the first decade of life. Cockayne syndrome II, or severe Cockayne syndrome, presents at birth with accelerated facial and somatic features. Individuals who are affected with Cockayne syndrome I typically have progressive neurologic degeneration with death occurring by the second or third decade of life, whereas patients with Cockayne syndrome II typically die by age 6-7 years.[2]

Also see the eMedicine pediatrics article, Cockayne Syndrome.

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Pathophysiology

Cockayne syndrome is an autosomal recessive disorder. A DNA repair defect is a prominent feature of Cockayne syndrome.

Cockayne syndrome, xeroderma pigmentosa, and trichothiodystrophy are 3 distinct syndromes with cellular sensitivity to ultraviolet (UV) irradiation. These syndromes arise from mutations of genes critical for nucleotide-excision repair and RNA transcription. At least 28 genes are involved in the nucleotide excision repair pathway, which is involved in protection against UV-induced DNA damage.[3, 4, 5]

Cockayne syndrome is not associated with skin cancer, despite the photosensitivity and DNA repair defect, unlike xeroderma pigmentosa. Trichothiodystrophy patients have sulfur-deficient brittle hair with a normal skin cancer risk. Progressive sensorineural deafness is an early feature of both Cockayne syndrome and xeroderma pigmentosa, but not trichothiodystrophy. Furthermore, the main neuropathology of xeroderma pigmentosa is a primary neuronal degeneration, while in Cockayne syndrome and trichothiodystrophy, myelination of the brain is reduced, suggesting that the neurological abnormalities may be caused by both developmental defects and faulty DNA repair of neuronal cells damaged by oxidative stress.[3, 4, 6]

Cockayne syndrome group A or B (CSA or CSB) genes are required for transcription-coupled repair, a subpathway of nucleotide-excision repair. At least 10 known CSA mutations have been characterized to date, primarily mutations in group 8 excision-repair cross-complementation gene (ERCC8) on band 5q12.[7] CSB gene defects (ERCC6) result in altered expression of antiangiogenic and cell cycle genes and proteins, particularly p21, which can result in inhibition of cell cycle progression and growth. These may account for signs and symptoms not readily related to DNA repair deficiencies.[8, 9]

See Causes.

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Epidemiology

Frequency

International

Cockayne syndrome is rare worldwide.

Mortality/Morbidity

Patients with Cockayne syndrome I have progressive, unremitting, neurologic deterioration usually leading to death by the second or third decade of life. Patients with Cockayne syndrome II typically have a worse prognosis, with death occurring earlier, typically by age 6 or 7 years.

Race

No racial predilection is reported for Cockayne syndrome.

Sex

No sexual predilection is described for Cockayne syndrome; the male-to-female ratio is equal.

Age

Cockayne syndrome I (CS-A) manifests in childhood. Cockayne syndrome II (CS-B) manifests at birth or in infancy, and it has a worse prognosis.

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Contributor Information and Disclosures
Author

Suguru Imaeda, MD  Chief of Dermatology, Yale University Health Services; Chief of Dermatology, West Haven Veterans Affairs Medical Center; Assistant Professor, Department of Dermatology, Yale University School of Medicine

Suguru Imaeda, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Connecticut State Medical Society, Sigma Xi, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Jacek C Szepietowski, MD, PhD  Professor, Vice-Head, Department of Dermatology, Venereology and Allergology, Wroclaw Medical University; Director of the Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Poland

Disclosure: Stiefel GSK Company Salary Employment; Orfagen Consulting fee Consulting; Maruho Consulting fee Consulting; Astellas Consulting fee Consulting; Abbott Consulting fee Consulting; Leo Pharma Consulting fee Consulting

David F Butler, MD  Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH  Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, University of Medicine and Dentistry of New Jersey-New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Disclosure: Nothing to disclose.

Catherine M Quirk, MD  Clinical Assistant Professor, Department of Dermatology, University of Pennsylvania

Catherine M Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD  Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

References

  1. Cockayne EA. Dwarfism with retinal atrophy and deafness. Arch Dis Child. 1936;11:1-8.

  2. Natale V. A comprehensive description of the severity groups in Cockayne syndrome. Am J Med Genet A. May 2011;155A(5):1081-95. [Medline].

  3. Chu G, Mayne L. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes explain the diseases?. Trends Genet. May 1996;12(5):187-92. [Medline].

  4. Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, DiGiovanna JJ. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience. Apr 14 2007;145(4):1388-96. [Medline].

  5. Ridley AJ, Colley J, Wynford-Thomas D, Jones CJ. Characterisation of novel mutations in Cockayne syndrome type A and xeroderma pigmentosum group C subjects. J Hum Genet. 2005;50(3):151-4. [Medline].

  6. Hayashi M, Miwa-Saito N, Tanuma N, Kubota M. Brain vascular changes in Cockayne syndrome. Neuropathology. Jul 12 2011;[Medline].

  7. Henning KA, Li L, Iyer N, et al. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH. Cell. Aug 25 1995;82(4):555-64. [Medline].

  8. Kleppa L, Kanavin OJ, Klungland A, Stromme P. A novel splice site mutation in the Cockayne syndrome group A gene in two siblings with Cockayne syndrome. Neuroscience. Apr 14 2007;145(4):1397-406. [Medline].

  9. Cleaver JE, Hefner E, Laposa RR, Karentz D, Marti T. Cockayne syndrome exhibits dysregulation of p21 and other gene products that may be independent of transcription-coupled repair. Neuroscience. Apr 14 2007;145(4):1300-8. [Medline].

  10. Bhojwani R, Lloyd IC, Alam S, Ashworth J. Blepharokeratoconjunctivitis in Cockayne syndrome. J Pediatr Ophthalmol Strabismus. May-Jun 2009;46(3):184-5. [Medline].

  11. Christiansen M, Thorslund T, Jochimsen B, Bohr VA, Stevnsner T. The Cockayne syndrome group B protein is a functional dimer. FEBS J. Sep 2005;272(17):4306-14. [Medline].

  12. Nardo T, Oneda R, Spivak G, et al. A UV-sensitive syndrome patient with a specific CSA mutation reveals separable roles for CSA in response to UV and oxidative DNA damage. Proc Natl Acad Sci U S A. Apr 14 2009;106(15):6209-14. [Medline].

  13. Tan WH, Baris H, Robson CD, Kimonis VE. Cockayne syndrome: the developing phenotype. Am J Med Genet A. Jun 1 2005;135(2):214-6. [Medline].

  14. Morris DP, Alian W, Maessen H, et al. Cochlear implantation in Cockayne syndrome: our experience of two cases with different outcomes. Laryngoscope. May 2007;117(5):939-43. [Medline].

  15. Wooldridge WJ, Dearlove OR, Khan AA. Anaesthesia for Cockayne syndrome. Three case reports. Anaesthesia. May 1996;51(5):478-81. [Medline].

  16. Yuen MK, Rodrigo MR, Law Min JC, Tong CK. Myocardial ischemia and delayed recovery after anesthesia in a patient with Cockayne syndrome: a case report. J Oral Maxillofac Surg. Dec 2001;59(12):1488-91. [Medline].

  17. Raghavendran S, Brown KA, Buu N. Perioperative management of patients with Cockayne syndrome - recognition of accelerated aging with growth arrest. Paediatr Anaesth. Apr 2008;18(4):360-1. [Medline].

  18. Hurwitz S. Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 2nd ed. Philadelphia, Pa: WB Saunders; 1993:96.

  19. Nance MA, Berry SA. Cockayne syndrome: review of 140 cases. Am J Med Genet. Jan 1 1992;42(1):68-84. [Medline].

  20. Ozdirim E, Topcu M, Ozon A, Cila A. Cockayne syndrome: review of 25 cases. Pediatr Neurol. Nov 1996;15(4):312-6. [Medline].

  21. Spitz JL. Genodermatoses. Vol 1. Baltimore, Md: Williams & Wilkins; 1996:208-9.

  22. Sybert VP. Genetic Skin Disorders. Vol 1. ed. New York, NY: Oxford University Press; 1997:559-61.

 
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