History

Patients with Cockayne syndrome usually appear normal at birth. Eventually, they present with a typical facial appearance of a pinched, narrow face and a beaked nose. Mental retardation, microcephaly, and growth failure become evident over time. Photosensitivity and progressive worsening neurologic signs and symptoms of ataxia and quick jerky movements are also noted.

In Cockayne syndrome I, the phenotypic features of Cockayne syndrome may be subtle early in the disease course. The signs become evident later in the first decade of life.

In CS-II, severe developmental delays are evident in the immediate postnatal period, and characteristic facies may be present by age 2 years.

Appearance and habitus in Cockayne syndrome

Microcephaly, a thin nose, and large ears give the patient a Mickey Mouse appearance.

Patients may be cachectic.

Skin findings in Cockayne syndrome

Photosensitive eruption with erythema and scale may be observed.

Affected areas show hyperpigmentation, telangiectasia, and atrophy.

Subcutaneous lipoatrophy results in sunken eyes and an aged progeric appearance.

Cyanotic acral edema of the extremities^[16]

Nail dystrophies and hair anomalies^[16]

Musculoskeletal findings in Cockayne syndrome

Microcephaly, short stature, long limbs with joint contractures, large hands and feet, kyphosis, thickened calvariae, sclerotic epiphyses of the fingers, and osteoporosis may be observed.

Neurologic findings in Cockayne syndrome

Intracranial calcifications and diffuse demyelination of the central nervous system and the peripheral nerves result in progressive neurologic deterioration, such as ataxia, tremors, and cog wheeling.

Mental retardation may be noted.

Progressive sensorineural deafness may occur.

Ophthalmologic findings in Cockayne syndrome ^[17]

Salt and pepper retinal pigment, miotic pupils, cataracts, optic atrophy, corneal opacity, and nystagmus may be observed.

Vision is preserved.

Blepharokeratoconjunctivitis has been reported.^[18]

Dental findings in Cockayne syndrome

Caries may be present.

Endocrinologic findings in Cockayne syndrome

Hypogonadism occurs in 30% of males.

Irregular menses occur in females.

Complications

In Cockayne syndrome, death by the second or third decade of life occurs as a result of progressive neurologic degeneration.

Differential Diagnoses

Cockayne EA. Dwarfism with retinal atrophy and deafness. Arch Dis Child. 1936. 11:1-8.
Natale V. A comprehensive description of the severity groups in Cockayne syndrome. Am J Med Genet A. 2011 May. 155A(5):1081-95. [QxMD MEDLINE Link].
Wilson BT, Stark Z, Sutton RE, Danda S, Ekbote AV, Elsayed SM, 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. [QxMD MEDLINE Link].
Chu G, Mayne L. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes explain the diseases?. Trends Genet. 1996 May. 12(5):187-92. [QxMD MEDLINE Link].
Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, DiGiovanna JJ. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience. 2007 Apr 14. 145(4):1388-96. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Hayashi M, Miwa-Saito N, Tanuma N, Kubota M. Brain vascular changes in Cockayne syndrome. Neuropathology. 2011 Jul 12. [QxMD MEDLINE Link].
Zhang WR, Garrett GL, Cleaver JE, Arron ST. Absence of skin cancer in the DNA repair-deficient disease Cockayne Syndrome (CS): A survey study. J Am Acad Dermatol. 2016 Jun. 74 (6):1270-2. [QxMD MEDLINE Link].
Scheibye-Knudsen M, Tseng A, Borch Jensen M, Scheibye-Alsing K, Fang EF, Iyama T, et al. Cockayne syndrome group A and B proteins converge on transcription-linked resolution of non-B DNA. Proc Natl Acad Sci U S A. 2016 Nov 1. 113 (44):12502-12507. [QxMD MEDLINE Link]. [Full Text].
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. 1995 Aug 25. 82(4):555-64. [QxMD MEDLINE Link].
Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum. Mech Ageing Dev. 2013 May-Jun. 134(5-6):161-70. [QxMD MEDLINE Link].
Calmels N, Botta E, Jia N, Fawcett H, Nardo T, Nakazawa Y, et al. Functional and clinical relevance of novel mutations in a large cohort of patients with Cockayne syndrome. J Med Genet. 2018 Mar 23. [QxMD MEDLINE Link].
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. 2007 Apr 14. 145(4):1397-406. [QxMD MEDLINE Link].
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. 2007 Apr 14. 145(4):1300-8. [QxMD MEDLINE Link].
Christiansen M, Thorslund T, Jochimsen B, Bohr VA, Stevnsner T. The Cockayne syndrome group B protein is a functional dimer. FEBS J. 2005 Sep. 272(17):4306-14. [QxMD MEDLINE Link].
Frouin E, Laugel V, Durand M, Dollfus H, Lipsker D. Dermatologic findings in 16 patients with Cockayne syndrome and cerebro-oculo-facial-skeletal syndrome. JAMA Dermatol. 2013 Dec. 149(12):1414-8. [QxMD MEDLINE Link].
Wu Y, Zheng Y, Yan X, Huang Y, Jiang Y, Li H. Ocular findings in a patient with Cockayne syndrome with two mutations in the ERCC6 gene. Ophthalmic Genet. 2016 May 17. 1-3. [QxMD MEDLINE Link].
Bhojwani R, Lloyd IC, Alam S, Ashworth J. Blepharokeratoconjunctivitis in Cockayne syndrome. J Pediatr Ophthalmol Strabismus. 2009 May-Jun. 46(3):184-5. [QxMD MEDLINE Link].
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. 2009 Apr 14. 106(15):6209-14. [QxMD MEDLINE Link]. [Full Text].
Tan WH, Baris H, Robson CD, Kimonis VE. Cockayne syndrome: the developing phenotype. Am J Med Genet A. 2005 Jun 1. 135(2):214-6. [QxMD MEDLINE Link].
Wilson BT, Strong A, O'Kelly S, Munkley J, Stark Z. Metronidazole Toxicity in Cockayne Syndrome: A Case Series. Pediatrics. 2015 Sep. 136 (3):e706-8. [QxMD MEDLINE Link].
Morris DP, Alian W, Maessen H, et al. Cochlear implantation in Cockayne syndrome: our experience of two cases with different outcomes. Laryngoscope. 2007 May. 117(5):939-43. [QxMD MEDLINE Link].
Van Wyhe RD, Emery CV, Williamson RA. Cochlear implantation in pediatric patients with Cockayne Syndrome. Int J Pediatr Otorhinolaryngol. 2018 Mar. 106:64-67. [QxMD MEDLINE Link].
Wooldridge WJ, Dearlove OR, Khan AA. Anaesthesia for Cockayne syndrome. Three case reports. Anaesthesia. 1996 May. 51(5):478-81. [QxMD MEDLINE Link].
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. 2001 Dec. 59(12):1488-91. [QxMD MEDLINE Link].
Raghavendran S, Brown KA, Buu N. Perioperative management of patients with Cockayne syndrome - recognition of accelerated aging with growth arrest. Paediatr Anaesth. 2008 Apr. 18(4):360-1. [QxMD MEDLINE Link].
Hurwitz S. Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 2nd ed. Philadelphia, Pa: WB Saunders; 1993. 96.
Spitz JL. Genodermatoses. Baltimore, Md: Williams & Wilkins; 1996. Vol 1: 208-9.
Sybert VP. Genetic Skin Disorders. 1st ed. New York, NY: Oxford University Press; 1997. Vol 1: 559-61.

Media Gallery

Autosomal recessive inheritance pattern.

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Author

Suguru Imaeda, MD Chief of Dermatology, Yale University Health Services; Chief of Dermatology, Veterans Affairs Connecticut Healthcare System; 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, The Scientific Research Honor Society, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Former Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Military Dermatologists, Phi Beta Kappa, Texas Dermatological Society

Disclosure: Nothing to disclose.

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, New York Academy of Medicine, Royal College of Physicians of Edinburgh, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

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: Received consulting fee from Orfagen for consulting; Received consulting fee from Maruho for consulting; Received consulting fee from Astellas for consulting; Received consulting fee from Abbott for consulting; Received consulting fee from Leo Pharma for consulting; Received consulting fee from Biogenoma for consulting; Received honoraria from Janssen for speaking and teaching; Received honoraria from Medac for speaking and teaching; Received consulting fee from Dignity Sciences for consulting; .

Cockayne Syndrome Clinical Presentation

History

Physical Examination