Cockayne Syndrome or also Progeria-Like-Syndrome

The Cockayne Syndrome is also called Progeria-Like-Syndrome. The symptoms of this disease are also very similar to those of Progeria Infiantilis and Werner Syndrome. However, there are several forms of Cockayne Syndrome and therefore they differ in nature and severity.

What is Cockayne Syndrome?

The Cokcayne Syndrome is a rare hereditary disease. This syndrome is one of the metabolic diseases that affect the central nervous system. This causes several serious symptoms, especially reduced growth and a rapid aging process in the body. The symptoms are partly similar to those of Progeria infantilis and Werner Syndrome. The difference, however, is that with Cockayne syndrome, in addition to physical, neurological and mental developments are disrupted.The name of the syndrome is named after Dr. Edward Alfred Cockayne. This doctor studied hereditary diseases in children. In 1933 he published the book “Inherited Abnormalities of the Skin and it’s Appendages” and in 1936 he described the Cockayne Syndrome.

Other names for Cockayne Syndrome are:

Progeria-Like-Syndrome
Neill-Dingwall Syndrome
Weber-Cockayne Syndrome
Dwarfism-Retinal Atrophy-Deafness Syndrome
Progeroid Nanism

How often and where does the syndrome occur?

Cockayne Syndrome occurs in 1 in 100,000 children worldwide. It is estimated that there are about 200-300 patients around the world. The syndrome is very rare in the Netherlands. It is seen more often in England and America.

Cause

In Cockayne Syndrome there is a defect in the NER system (DNA clearance system). This is caused by a mutation in the genes:

CSA (Cockayne Syndrome A): Due to the mutation in this gene, the damage in the DNA cannot be repaired. The damaged DNA cells are therefore broken down. They no longer have a function. This explains the rapid aging symptoms of Cockayne Syndrome. Other names for this gene are ERCC8 or CKN1
CSB (Cockayne Syndrome B): a mutation in this gene leads to hypersensitivity to UV light. Other names for this gene are ERCC6 or CKN2

The NER system.To keep the DNA intact, cells are equipped with various DNA repair mechanisms. One of these is the NER system. NER stands for Nucleotide Excision Repair . The NER system ensures that damage caused by, among other things, UV radiation and cigarette smoke is removed. A congenital defect in the NER system is mainly characterized by a range of physical and mental abnormalities. This is the case with Cockayne Syndrome.The hereditary pattern of Cockayne Syndrome is autosomal recessive. Autosomal means that it occurs equally often in boys and girls. Recessive means that the disease only occurs when both parents pass on the affected gene to their child. Only then can the child contract the disease.

Different shapes

The Cockayne Syndrome can be classified into three types.

Type I : This form is also called “Classical Cockayne Syndrome” or “Late Onset Cockayne Syndrome”. The symptoms become visible within the second year of life.
Type II : This form is also called “Congenital Cockayne Syndrome” or “Early Onset Cockayne syndrome”. The symptoms occur within the first year of life. Cataracts are often one of the first symptoms.
Type III : This is the mild form and often occurs later in childhood. The children show only some symptoms of Cockayne Syndrome. Sometimes there is a combination with “Xeroderma Pigmentosum”, a hereditary skin disease.

Xeroderma Pigmentosum (XP): a rare hereditary skin disease with strong hypersensitivity to UV light (especially sunlight), with a risk of developing skin cancer at a later stage.

Symptoms

Types I, II and III have similar symptoms, which can change in severity depending on the type.

Characteristic features:

The eyes are set deep in the face
Large (deformed) ears
The nose is striking (excellent)
Relatively long arms and legs
The patients are noticeably short in height
Often small head, but can also be too big.

Symptoms that (may) occur:

Delayed development of gross and fine motor skills
Delayed language development
Delayed speech (often slurred)
Crooked growth of the spine
Huge growth retardation
Learning disability (very low IQ)
Retardation of puberty
Cold hands and feet.
Spasticity
Hypersensitivity to sunlight
Visually impaired
Cataract
Glaucoma (green cataracts) resulting in blindness
Hair loss (little hair)
Tooth loss (often tooth decay)
Pigment spots
Skin infections
Skin rash
Hearing loss (often severe)
Limited mobility of joints (often due to inflammation)
Breathing problems
Decreased sweat secretion

Diagnosis

Cockayne Syndrome can be diagnosed by certain tests.

Via an MRI/CT scan: thickening of the skull roof, calcification, poorly developed white brain matter, disappearance of nerve fibers, decrease in mass in the cerebellum and inflammation of the meninges.
Via an X-ray: narrow diaphragm and narrow ribs and osteoporosis (bone destruction)
Via a nerve test: disturbed nerve conduction, whereby the stimulus transmission is delayed.
Through a special test: by examining cells via a skin biopsy (a piece of skin is removed). The cells are tested for sensitivity to UV light. RNA and DNA synthesis after UV damage is examined. This is reduced in Cockayne Syndrome.

Prognosis

Children with Cockayne Syndrome age prematurely. They have a low life expectancy. However, depending on the type they have. Patients with Type I live an average of 10 to 20 years. Patients with Type II have a short life expectancy, on average 5 years. Type III is milder in form and these patients therefore live slightly longer.However, there is a major dispute about life expectancy, because a patient is now known to be 31 years old. There also appears to be a patient with Type I who is now over 12.The cause of death is often the consequences of very diverse complications and combined factors.

Therapy

There is no specific treatment for patients with Cockayne Syndrome. So far there is no cure. However, medical scientists are developing a drug “DNage”, which slows down aging.

A number of important points of attention:

Avoid sunlight! (this prevents even more damage to the body)
Glasses for visually impaired people
A hearing aid for hearing loss.
Cataract surgery (lens replaced)
Speech therapy to improve language and speech development.
Special education (difficulty learning)
Good warm clothing in winter (prevents painful stiff joints)
Regular check-ups by the dentist.
Physiotherapy to stimulate motor skills.

Interest group for Cockayne Syndrome.

There is an American association that represents the interests of patients and their parents with Cockayne Syndrome. This is called: Share and Care Cockayne Syndrome Network’. The aim of this is to exchange experiences between families and professionals. Their mission is also to investigate the precise cause and cure of the syndrome.