Cockayne Syndrome

What is Cockayne Syndrome?

The condition known as Cockayne Syndrome is a rare form of dwarfism that has specific features. Symptoms presenting in this disorder starts in the infancy stage and have known to worsen as the child ages ^{[1, 2]}.

Cockayne syndrome (CS) is a hereditary medical disorder that is known to have distinct characteristics. Patients who are afflicted by this syndrome are found to have microcephaly or disproportionately small head, having a short built due to a delay in their physical growth and retarded intellectual development.

This syndrome results from mutations in the ERCC6 or ERCC8 gene. The genetic error may have been caused by ultraviolet damage, radiation, intake of toxic chemicals and free radicals. Annual incidence of CS is current at about 1/200,000 in European countries. Prognosis of cockayne syndrome is poor and its life expectancy is between 20-30 years of age depending on the type of CS. Figure 1 shows an example of an individual with CS ^{[1, 2, 3]}.

Figure 1- A person with Cockayne Syndrome

Types

There are several types of CS depending on the age of onset and the symptoms that the person is manifesting ^{[1, 2, 4]}.

The first type is CS type I or moderate CS. In this form, there is normal development prenatally with the abnormalities manifesting in the child’s first 2 years of life. These symptoms worsen and may cause severe disability. These individuals may live up to 20 years of age ^{[2, 4]}.

Cockayne syndrome type 2 is also known as severe or early-onset CS. These children manifest the symptoms at birth and they will present either a small amount or no neurologic development postnatally. They have a shorter lifespan and may only survive for up to 7 years of age ^{[2, 4]}.

Mild CS is the third known type of this condition. Patients with this variation will have normal physical and cognitive development during the early years of life. The symptoms will start manifesting at a later age ^[4].

The fourth type of CS is called Xeroderma pigmentosum-Cockayne syndrome (XP-CS). Aside from the symptoms associated with CS, the patient will exhibit freckling on the face and develop early skin cancers which are typical of Xeroderma pigmentosum ^{[1, 4]}.

Signs and symptoms

Apart from the distinctive features of CS, there are other symptoms that will exhibit by the patient depending on the CS variation that they have ^{[3, 4, 5]}.

Those with CS type I will have a height and weight that belongs to the 5th percentile due to the developmental delay. They will also develop vision and hearing problems due to the dysfunction of their nervous system. These will continue to deteriorate and will result in severe disability ^{[3, 4, 5]}.

Severe CS may cause postnatal spine contractures in their early years which will lead to either scoliosis or kyphosis. There may also be a structural anomaly in their eyes or a congenital cataract may develop ^{[3, 4, 5]}.

Patients with the milder form of CS will have normal development until the symptoms similar with CS type I appear at a later age ^{[4, 5]}.

The symptoms present in those with XP-CS is a combination of what is typically found in these 2 conditions. The freckling and appearance of early skin cancers will be accompanied by sexual underdevelopment, short stature and intellectual development delay ^{[4, 5]}.

Other symptoms that may be present include increased sensitivity to light, wrinkling of the skin due to the absence of fat under the skin and increased amount of pigmentation in their skin ^[5].

Diagnosis

Health history and physical examination

The primary reason for consultation is usually the presence of physical and intellectual delay in the child. The physician will evaluate the development of the child to assess the severity of the condition. Family history may also be elicited to assist in the establishment of the diagnosis ^{[1, 5]}.

Molecular genetic testing

Once the physician has identified the delay, a molecular genetic testing may be performed. This test is useful regardless of the CS variation and may detect mutations in the genes associated with CS. Mutations in the gene ERCC6 accounts for 65% of total CS cases while ERCC8 gene mutation accounts for 35%. The mutations maybe identified through DNA sequence analysis or deletion and detection analysis ^{[4, 5]}.

Treatment

Symptom management

The management for CS is symptomatic and supportive. Physical therapy and the use of assistive devices may be recommended to those who have developed abnormalities in their gait. Medication such as baclofen and carbidopa-levodopa may be prescribed to relieve spasticity and tremor respectively.

Education program that is tailored to the needs of the patient may be able to address the developmental delay. A gastrostomy tube may be placed to patients who are unable to feed themselves.

The development of hearing loss and cataracts are managed accordingly to decrease the effect the condition have on the patient. Sunscreens and sunglasses will be used to address the patient’s increased sensitivity to light ^{[1, 2, 4, 5]}.

Complication prevention

Complications may be prevented by continuous physical therapy to prevent the development of joint contractures. Dental management should be performed aggressively to decrease the possibility of dental caries development. Assessment of the home environment may be required to prevent any episodes of fall.

Annual reassessment of the patient’s condition is also essential to monitor the progression of the condition and manage the developing complication in a timely manner ^{[4, 5]}.
References

1. Dollfus, H., & Vincent, L. (2009, May). Cockayne Syndrome. Retrieved from Orpha.net: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=191
2. Genetics Home Reference. (2016, August 30). Cockayne Syndrome. Retrieved from Genetics Home Reference: https://ghr.nlm.nih.gov/condition/cockayne-syndrome#diagnosis
3. Imaeda, S. (2014, February 28). Cockayne Syndrome. Retrieved from eMedicine: http://emedicine.medscape.com/article/1115866-followup#e3
4. Laugel, V. (2000, December 28). Cockayne Syndrome. Retrieved from GeneReviews: http://www.ncbi.nlm.nih.gov/books/NBK1342/
5. National Organization for Rare Diseases. (2007). Cockayne Syndrome. Retrieved from National Organization for Rare Diseases: http://rarediseases.org/rare-diseases/cockayne-syndrome/