Genetics of Cockayne Syndrome Workup

  • Author: David Flannery, MD, FAAP, FACMG; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Mar 12, 2012
 

Laboratory Studies

  • In patients with suspected Cockayne syndrome (CS), perform routine laboratory tests to exclude other disorders and to establish baseline renal function.
  • Request chromosome analysis to exclude any karyotypic abnormalities associated with growth failure.
  • Request chromosome breakage studies if considering Bloom syndrome in the differential diagnosis. Patients with xeroderma pigmentosum (a differential diagnosis for Cockayne syndrome type 1 [CKN1]) and Bloom syndrome demonstrate clinical phenotypes that overlap with those found in patients with Cockayne syndrome. Chromosome breakage studies and DNA mutation analysis are necessary to exclude Bloom syndrome and xeroderma pigmentosum.
  • Cultured skin fibroblasts of patients with CKN1 lack the ability to form colonies when subjected to UV irradiation. Very few laboratory personnel have expertise in this technique.
  • Mutational analysis of the gene associated with Cockayne syndrome is available on a research basis only.
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Imaging Studies

  • CT scan or MRI findings include increased ventricular size, cerebral atrophy, white matter abnormalities, and normal pressure hydrocephaly.
  • Skeletal radiographs depict vertebral body and pelvic abnormalities.
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Other Tests

  • Audiometry is used to determine if sensorineural hearing loss is present.
  • Electroencephalography is used to assess the patient for seizure activity.
  • Electroretinography reveals abnormalities in the electric potential of the retina.
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Histologic Findings

  • Ocular histopathologic findings indicate degeneration of all retinal layers. Pigment migrates into the photoreceptor layer. Nerve fiber bundles of the optic nerve head become markedly thin, while partial demyelination of the remaining nerves occurs.
  • For patients with sensorineural hearing loss, a significant loss of neurons occurs in the spiral ganglion and brainstem, with retrograde atrophy of the auditory pathways.
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Contributor Information and Disclosures
Author

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Elaine H Zackai, MD  Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia

Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate/Craniofacial Association, American College of Medical Genetics, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David Flannery, MD, FAAP, FACMG  Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia

David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

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  2. Laugel V, Dalloz C, Durand M, et al. Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Hum Mutat. Nov 5 2009;[Medline].

  3. Zhang H, Gao J, Ye J, Gong Z, Gu X. Maternal origin of a de novo microdeletion spanning the ERCC6 gene in a classic form of the Cockayne syndrome. Eur J Med Genet. Jul-Aug 2011;54(4):e389-93. [Medline].

  4. [Guideline] Cunniff C. Prenatal screening and diagnosis for pediatricians. Pediatrics. Sep 2004;114(3):889-94. [Medline].

  5. Cao H, Williams C, Carter M, Hegele RA. CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common polymorphism. J Hum Genet. 2004;49(1):61-3. [Medline].

  6. Chien YH, Chou HC, Hwu WL. Cockayne syndrome in a family. Acta Paediatr Taiwan. Jan-Feb 2002;43(1):46-9. [Medline].

  7. Cleaver JE, Thompson LH, Richardson AS, States JC. A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Hum Mutat. 1999;14(1):9-22. [Medline].

  8. Greenhaw GA, Hebert A, Duke-Woodside ME, et al. Xeroderma pigmentosum and Cockayne syndrome: overlapping clinical and biochemical phenotypes. Am J Hum Genet. Apr 1992;50(4):677-89. [Medline].

  9. Higginbottom MC, Griswold WR, Jones KL, et al. The Cockayne syndrome: an evaluation of hypertension and studies of renal pathology. Pediatrics. Dec 1979;64(6):929-34. [Medline].

  10. Kleijer WJ, van der Sterre ML, Garritsen VH. Prenatal diagnosis of the Cockayne syndrome: survey of 15 years experience. Prenat Diagn. Oct 2006;26(10):980-4. [Medline].

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  12. Mathur R, Chowdhury MR, Singh G. Recent advances in chromosome breakage syndromes and their diagnosis. Indian Pediatr. Jun 2000;37(6):615-25. [Medline].

  13. Moyer DB, Marquis P, Shertzer ME, Burton BK. Cockayne syndrome with early onset of manifestations. Am J Med Genet. Oct 1982;13(2):225-30. [Medline].

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  15. Proops R, Taylor AM, Insley J. A clinical study of a family with Cockayne's syndrome. J Med Genet. Aug 1981;18(4):288-93. [Medline].

  16. Rapin I, Weidenheim K, Lindenbaum Y. Cockayne syndrome in adults: review with clinical and pathologic study of a new case. J Child Neurol. Nov 2006;21(11):991-1006. [Medline].

  17. Ren Y, Saijo M, Nakatsu Y, et al. Three novel mutations responsible for Cockayne syndrome group A. Genes Genet Syst. Feb 2003;78(1):93-102. [Medline].

  18. Sugita T, Ikenaga M, Suehara N, et al. Prenatal diagnosis of Cockayne syndrome using assay of colony-forming ability in ultraviolet light irradiated cells. Clin Genet. Sep 1982;22(3):137-42. [Medline].

  19. 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].

  20. Traboulsi EI, De Becker I, Maumenee IH. Ocular findings in Cockayne syndrome. Am J Ophthalmol. Nov 15 1992;114(5):579-83. [Medline].

  21. Venema J, Mullenders LH, Natarajan AT, et al. The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA. Proc Natl Acad Sci U S A. Jun 1990;87(12):4707-11. [Medline].

 
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Autosomal recessive inheritance pattern.
 
 
 
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