Cockayne syndrome
A rare autosomal‑recessive disorder marked by microcephaly, growth failure, photosensitivity, and multisystem degeneration that appears in infancy and worsens over time.
Overview
Cockayne syndrome is a rare disorder characterized by an abnormally small head size (microcephaly), a failure to gain weight and grow at the expected rate (failure to thrive) leading to very short stature, and delayed development. The signs and symptoms are usually apparent from infancy and worsen over time. Most affected individuals have an increased sensitivity to sunlight (photosensitivity); even minimal sun exposure can cause sunburn or blistering of the skin. Additional manifestations often include hearing loss, vision loss, severe tooth decay, bone abnormalities, constantly cold hands and feet, and brain changes visible on imaging.
People with Cockayne syndrome have a serious reaction to the antibiotic metronidazole; ingestion can cause life‑threatening liver failure.
Cockayne syndrome is sometimes divided into types I, II, and III based on severity and age of onset, though the boundaries are not always clear. Type II, also called cerebro‑oculo‑facio‑skeletal (COFS) syndrome, may be considered a separate but related condition or part of the same spectrum.
Frequency
Cockayne syndrome is estimated to occur in 2 to 3 per million newborns in the United States and Europe.
Causes & Risk Factors
The condition results from mutations in either the ERCC6 gene (also known as CSB) or the ERCC8 gene (also known as CSA). These genes encode proteins involved in DNA repair. Normally, cells fix DNA damage caused by ultraviolet (UV) rays, toxic chemicals, radiation, and free radicals. In individuals with Cockayne syndrome, DNA damage is not repaired properly, leading to accumulated errors, cellular malfunction, and cell death. Faulty DNA repair underlies the photosensitivity and is suspected to contribute to other features of the disorder, though the exact mechanisms remain unclear.
Genes associated with Cockayne syndrome
- ERCC6
- ERCC8
Inheritance
This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell carry mutations. Parents of an affected individual each carry one copy of the mutated gene but typically do not show signs or symptoms.
Other Names
- CS
- Dwarfism‑retinal atrophy‑deafness syndrome
Additional Information & Resources
Genetic Testing
- Genetic Testing Registry: Cockayne syndrome
Patient Support and Advocacy
- National Organization for Rare Disorders (NORD)
Clinical Trials
- ClinicalTrials.gov
Catalog of Genes and Diseases (OMIM)
- CEREBROOCULOFACIOSKELETAL SYNDROME 1; COFS1
- COCKAYNE SYNDROME A; CSA
- COCKAYNE SYNDROME B; CSB
Scientific Articles (PubMed)
- Cleaver JE, Lam ET, Revet I. Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. Nat Rev Genet. 2009 Nov;10(11):756‑68.
- Laugel V. Cockayne Syndrome. 2000 Dec 28 [updated 2024 Aug 29]. In: GeneReviews®.
- Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum. Mech Ageing Dev. 2013 May‑Jun;134(5‑6):161‑70.
- Nance MA, Berry SA. Cockayne syndrome: review of 140 cases. Am J Med Genet. 1992 Jan 1;42(1):68‑84.
- Weidenheim KM, Dickson DW, Rapin I. Neuropathology of Cockayne syndrome: Evidence for impaired development, premature aging, and neurodegeneration. Mech Ageing Dev. 2009 Sep;130(9):619‑36.
- Wilson BT, Stark Z, Sutton RE, et al. The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care. Genet Med. 2016 May;18(5):483‑93.
- Wilson BT, Strong A, O'Kelly S, et al. Metronidazole Toxicity in Cockayne Syndrome: A Case Series. Pediatrics. 2015 Sep;136(3):e706‑8.