Cockayne syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Cockayne syndrome is a rare disorder characterized by an abnormally small head size (microcephaly), an inability to gain weight and grow at the expected rate (faltering weight), very short stature, and delayed development. The signs and symptoms of this condition are usually apparent from infancy, and they worsen over time. Most affected individuals have an increased sensitivity to sunlight (photosensitivity), and in some cases even a small amount of sun exposure can cause a sunburn or blistering of the skin. Other signs and symptoms often include hearing loss, vision loss, severe tooth decay, bone abnormalities, hands and feet that are cold all the time, and changes in the brain that can be seen on brain scans.

People with Cockayne syndrome have a serious reaction to an antibiotic medication called metronidazole. If affected individuals take this medication, it can cause life-threatening liver failure.

Cockayne syndrome is sometimes divided into types I, II, and III based on the severity and age of onset of symptoms. However, the differences between the types are not always clear-cut, and some researchers believe the signs and symptoms reflect a spectrum instead of distinct types. Cockayne syndrome type II is also known as cerebro-oculo-facio-skeletal (COFS) syndrome, and while some researchers consider it to be a separate but similar condition, others classify it as part of the Cockayne syndrome disease spectrum.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Cockayne syndrome can result from mutations in either the ERCC6 gene (also known as CSB) or the ERCC8 gene (also known as CSA). These genes provide instructions for making proteins that are involved in repairing damaged DNA. DNA can be damaged by ultraviolet (UV) rays from the sun and by toxic chemicals, radiation, and unstable molecules called free radicals. Cells are usually able to fix DNA damage before it causes problems. However, in people with Cockayne syndrome, DNA damage is not repaired normally. As errors build up in DNA, cells malfunction and eventually die. The faulty DNA repair underlies photosensitivity in affected individuals, and researchers suspect that it also contributes to the other features of Cockayne syndrome. It is unclear how ERCC6 or ERCC8 gene mutations cause all of the varied features of this condition.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Cockayne syndrome is estimated to occur in 2 to 3 per million newborns in the United States and Europe.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of retinal pigmentation · Very frequent (99-80%)

Any deviation from the normal pigmentation of the retina.

Atypical behavior · Very frequent (99-80%)

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.

Cachexia · Very frequent (99-80%)

Severe weight loss, wasting of muscle, loss of appetite, and general debility related to a chronic disease.

Cerebellar atrophy · Very frequent (99-80%)

Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.

Cerebral dysmyelination · Very frequent (99-80%)

Defective structure and function of myelin sheaths of the white matter of the brain.

Growth delay · Very frequent (99-80%)

A deficiency or slowing down of growth pre- and postnatally.

Mental deterioration · Very frequent (99-80%)

Loss of previously present mental abilities, generally in adults.

Pigmentary retinopathy · Very frequent (99-80%)

An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.

Postnatal growth retardation · Very frequent (99-80%)

Slow or limited growth after birth.

Progressive microcephaly · Very frequent (99-80%)

Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.

Progressive sensorineural hearing impairment · Very frequent (99-80%)

A progressive form of sensorineural hearing impairment.

Severe short stature · Very frequent (99-80%)

A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.

Abnormal eye morphology · Frequent (79-30%)

A structural anomaly of the globe of the eye, or bulbus oculi.

Ataxia · Frequent (79-30%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Other findings in the same source

From: Orphanet

Additional reported features include Basal ganglia calcification (Frequent (79-30%)); Carious teeth (Frequent (79-30%)); Cataract (Frequent (79-30%)); Cerebral atrophy (Frequent (79-30%)); Cerebral calcification (Frequent (79-30%)); Cognitive impairment (Frequent (79-30%)); Congenital contracture (Frequent (79-30%)); Cutaneous photosensitivity (Frequent (79-30%)); Decreased nerve conduction velocity (Frequent (79-30%)); Deeply set eye (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Cockayne syndrome is Clinical Genetics, with a clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the exact genetic or chromosome finding explain the observed features?
• Would a genetic counsellor help the family understand the result?
• Which organ-specific assessments are appropriate for this particular diagnosis?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Cockayne syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.