Genetics of Cockayne Syndrome 

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

Background

Cockayne syndrome (CS) spans a spectrum that includes Cockayne syndrome type 1, the classic form; Cockayne syndrome type 2, a more severe form with symptoms present at birth (ie, cerebrooculofacial-skeletal [COFS] syndrome, Pena-Shokeir type 2 syndrome); Cockayne syndrome type 3, a milder form; and xeroderma pigmentosa–Cockayne syndrome (XP-CS). The discussion in this article is limited to Cockayne syndrome types 1 and 2, also termed Cockayne syndrome types A and B, respectively.

Cockayne syndrome type 1 (CKN1; Online Mendelian Inheritance in Man [OMIM] number 216400) and Cockayne syndrome type 2 (CSB; OMIM number 133540) are rare autosomal recessive disorders that feature growth deficiency, premature aging, and pigmentary retinal degeneration along with a complement of other clinical findings. Cockayne syndrome type 1 presents at birth, whereas Cockayne syndrome type 2 appears during early childhood. CKN1 was first reported in 1936. Fatality usually occurs in early adolescence, but some patients survive until early adulthood.

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Pathophysiology

Premature aging is the cardinal feature of both types; however, within the first 2 years of life, growth and development become abnormal. By the time the disease has fully manifested, height, weight, and head circumference are far below the fifth percentile. The characteristic physical appearance of cachectic dwarfism with thinning of the skin and hair, sunken eyes, and a stooped standing posture illustrates the aging process. Pathologic studies reveal diffuse and extensive demyelination in the central and peripheral nervous systems. Patients demonstrate pericapillary calcifications in the cortex and basal ganglia at an early age; severe neuronal loss in the cerebral cortex and cerebellum also occurs. These changes correlate with the physiologic changes of aging.

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Epidemiology

Frequency

United States

Incidence is less than 1 case per 250,000 live births.

Mortality/Morbidity

Patients are at risk for postnatal growth failure, pigmentary retinal degeneration, and premature death before adulthood.

  • Postnatal growth failure: Profound growth failure begins within the first year of life. Weight is affected more than length, and cachectic dwarfism results. A rare subset of patients, classified as having severe CKN1, have low birth weight with almost no postnatal growth.
  • Pigmentary retinal degeneration: This diagnostic criterion for CKN1 (salt-and-pepper appearance in the retinas) develops later in life. Cataracts are the second most common eye finding.
  • Premature death: The characteristic appearance of aging in children with Cockayne syndrome is striking. The mean and median age of death is 12 years, and most patients die as a result of pneumonia or other respiratory infections.

Race

CNK1 is panethnic.

Sex

Male-to-female ratio is 1:1, which is consistent with an autosomal recessive disorder. The pattern of autosomal recessive inheritance is illustrated in the image below.

Autosomal recessive inheritance pattern. Autosomal recessive inheritance pattern.

Age

As a progressive congenital disorder, clinical symptoms may not be manifested until late infancy or early childhood.

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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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Autosomal recessive inheritance pattern.
 
 
 
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