The clinical spectrum shows great variability in the severity and age of onset of manifestations. The most common form of Cockayne syndrome (type I) occurs during the first year of life. Cases of earlier onset with more severe symptoms (type II) and later onset cases with more moderate symptoms (type III) have also been described.

Common Disease Signs

Growth Disorders and Physical Features

Progressive growth retardation occurs between 1 and 2 years with low weight, small height for age, and microcephaly. Dysmorphic features include a face long, a small protruding chin, sunken eyes, and big ears. As the child grows older, the face appears prematurely old, the body is very thin (cachectic), and the limbs are thin and slender.

Neurological Disorders and Intellectual Deficit

These signs appear and progressively worsen. They include walking difficulties, unstable gait, balance disorders, ataxia, tremor, and lower limb spasticity. Sometimes, the arms and legs remain permanently flexed. The muscles are often insufficiently tonic (hypotonia), and the reflexes are abnormal. Some children have epilepsy. The majority of children have intellectual difficulties, sometimes very severe. Speech is often hacked and difficult to understand.

Eye Abnormalities

Anophthalmia is common because of the disappearance of the fat that is normally behind the eyeball. The first signs of impaired vision may be photophobia, nystagmus, or strabismus. The decline in vision may be related to cataract, atrophy of the optic retinopathy pigmentary nerve. Uveitis or conjunctivitis may also appear and aggravate the seeing disorders.

Hearing Disorders

They appear in early childhood and result in hypoacusia, which progresses and can evolve into profound deafness where the child perceives almost no sound.

Sun Sensitivity

Children have very thin skin and sensitive to ultraviolet rays; the slightest exposure causes severe sunburns that can sometimes leave scars or hyperpigmented spots. This photosensitivity also concerns the eyes.

Dental Abnormalities

The milk teeth may appear late, be small, irregular, and spaced. Later, they are not always replaced by a definitive tooth (dental agenesis).

Sometimes the teeth remain small (dental hypoplasia) or are poorly or anarchically implanted. Children are more susceptible to cavities than average.

Other Events

The disease can affect the liver. This is mostly asymptomatic and only manifested by elevated plasma levels of transaminases. Sometimes the physical examination shows hepatomegaly.

Kidney damage may occur in some children and manifest as proteinuria. Sometimes, it results in high blood pressure.

Boys may have unusually small testicles and penises (hypogonadism). Chryptorchidism is also possible.[9][10][11][3][12][13][14][15]

The suspected diagnosis should be confirmed by an analysis that measures the rate of DNA repair on skin cells (fibroblasts). This technique is done on skin specimen taken by biopsy. The fibroblasts will be cultured and then exposed to ultraviolet rays to measure the rate of repair of their DNA. In some diseases, such as Cockayne syndrome the test shows a lower than normal repair rate.

The genetic test, in other words, the search for the ERCC6 or ERCC8 gene mutation, is possible from a blood sample. The examination is performed in specialized laboratories.[16]

The management of the Cockayne syndrome must start as soon as possible and be multidisciplinary. It is symptomatic and aims primarily to prevent complications.

Feeding Assistance

Most babies need help to feed themselves enough during the first months of life. Muscle weakness and neurological impairment may prevent some children from eating enough. The use of a nasogastric tube or even gastrostomy is sometimes necessary.

Treatment of Ocular Anomalies

Cataract can be treated through surgery to remove the opaque lens. Implantation of a transparent artificial lens (graft) is not recommended.

Strabismus, when it exists, must be taken care of very early. The treatment is based on re-education sessions with the help of an orthoptist. The masking of the healthy eye (occlusion), by an eye mask or an opaque eyeglass lens, makes it possible to force the affected eye to work. Surgery may be necessary to remove or reduce a persistent deviation.

Dental Care

A dentist should regularly monitor children because of their sensitivity to caries. This will provide the appropriate care as needed.

Prevention Against the Sun's Harmful Effects

Affected individuals need to protect themselves from UV light. It should also be known that some artificial lights, including neon and halogen, emit harmful UV radiation which patients must be protected. It is recommended to wear hats with large brim, clothes that do not let the UV, closed collars. Similarly, the use of sunscreen with a 50 or greater sun protection factor during activities and trips outside is recommended, even in winter or late afternoon when the brightness seems low.

The eyes must also be protected by special glasses or a mask filtering the UV.

Other Measures

Hearing disorders may require the introduction of auditory prosthesis. The equipment must be accompanied by orthopneic sessions which must begin early. This re-education is also essential in the acquisition of reading and writing.

Most patients require psychomotor rehabilitation and physiotherapy appropriate to the degree of their impairment. Some equipment may be necessary to maintain and support the body in a good position (corset for example) and allow movement (canes, walker, wheelchair).

Specific socio-educational support is necessary in case of deficit intellectual. It takes into account personality, age, intellectual level, and behavioral characteristics of the child. Psychological support is also needed.[9][10][12][13][14][15][17][18]

The differential diagnosis is mainly with the other syndromes which are also characterized by photosensitivity and premature aging:

• Xeroderma pigmentosum
• Progeria
• Bloom syndrome
• Werner Syndrome
• Rothmund-Thomson Syndrome[3][17]

Cockayne syndrome causes obstacles to the motor, sensory, and intellectual plans. Children with the most common form of Cockayne syndrome (type 1) have very good communication skills for a very long time despite the illness and very often seek contact. Their socialization and schooling should be encouraged as much as possible. On the other hand, children with the severe form (type 2) have little possibility of interaction with their surroundings because of the severity of sensory and intellectual impairment. The lives of patients with a lighter form (type 3) are close to normal early on, and children attend formal schooling.

In adolescence, the appearance of visual and auditory problems and general weakness require adaptation of the pace of life.[15][17][18]

Cockayne syndrome is a rare but serious genetic disorder whose pathophysiological mechanisms remain unclear. Future goals are to understand how the proteins made by the ERCC6 and ERCC8 genes work in cells and how their dysfunction causes this syndrome. By understanding these mechanisms, new treatments may be discovered.

Studies are underway to identify and specify the characteristics of neurological disorders, including through MRI, which may better diagnose the syndrome.[6][7]

Cockayne syndrome is a rare genetic disease that causes severe motor, sensory, and intellectual disabilities. It requires interprofessional medical management and continuous care and supervision with frequent hospitalizations. Patients need clear information about their illness and scalability, psychological support, and social security coverage. Financial, technical, and administrative concerns sometimes compound these difficulties. The supervision and ongoing care that sick children need also have repercussions on their working lives (absenteeism, parental leave, part-time work). As for patients, their social integration and schooling depend on their physical abilities and development. (Level V)