Patients who have the Cockayne Syndrome show the following [4]:

Poor feeding

This is seen during infancy but in many cases, the diagnosis is not made at this point.

Photosensitive rashes

More than 75% of individuals with this condition exhibit photosensitivity. Other skin related findings include thin dry hair, dry scaly skin and decreased amount of subcutaneous tissue.

Cataracts

Severe form of CS I is what brings about the presence of cataracts in children who are younger than 3 years of age. This shows a poorer prognosis and in many cases it leads to early death.

General delay in psychomotor development

All individuals with category I Cockayne Syndrome exhibit mental retardation. This delay in psychomotor development becomes very visible around the age when speech and walking are expected to start developing.

Others

Generally, growth failure including progressive microcephaly is visible in most patients of the Cockayne type I within the first year.

According to neurologic examination patients show abnormal gait coupled with increased or decreased muscle tone and reflexes [5]. The abnormal gait is due to contractures of the ankles, knees and hips as well as leg spasticity and ataxia.

Another important characteristic of this disorder is pigmentary degeneration of the retina. Optic disk pallor and optic atrophy is also frequent. The changes in ophthalmology are often progressive.

Sensorineural hearing loss is present in more than 50% of patients with this condition. Dental caries is equally common as the root in permanent teeth of patients is often short [6]. Photodermatitis which leads to dry scaly skin is seen in most patients. The aged appearance is as a result of this disease process.

In some patients, there is decreased creatinine clearance but this rarely requires medical treatment. Structural irregularities in the renal system are not regularly reported. Testicular hypoplasia or cryptorchidism affects more than 30% of male patients [7]. Females menstruate but the cycles are not regular. Puberty is delayed in both sexes in certain cases.

• Splenomegaly

  This is a description of a three-year-old boy with typical features of Cockayne syndrome complicated with tetralogy of Fallot, pneumonia and hepato-splenomegaly. [ncbi.nlm.nih.gov]

  Micropenis, cryptorchidism, hepatomegaly, splenomegaly, osteoporosis, hypertension and altered renal function have also been reported in some CS patients (Jones, 1997). A second type of CS (type II or B), has been reported in 20 cases. [scielo.br]

• Progressive Intellectual Disability 

  intellectual disability with cerebral leukodystrophy, microcephaly, progressive pigmentary retinopathy, sensorineural deafness photosensitivity and possibly orofacial and dental anomalies. [ncbi.nlm.nih.gov]

  […] cachectic dwarfism, progressive intellectual disability with cerebral leukodystrophy, microcephaly, progressive pigmentary retinopathy, sensorineural deafness photosensitivity and possibly orofacial and dental anomalies. […] Télécharger l’article (pdf [genosmile.eu]

• Multiple Congenital Anomalies

  A frequent multiple congenital anomaly/mental retardation syndrome of unknown etiology which affects 1/10,000 newborn infants. [icd10data.com]

• Failure to Thrive

  Of these, failure to thrive, photosensitivity, and intellectual disability (language delays) developed before 2 or 3 years of age, whereas deafness, sunken eyes, and basal ganglia calcification on CT occurred later. [ncbi.nlm.nih.gov]

  Failure to thrive and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are other very common features. The underlying disorder is a defect in a DNA repair mechanism. [snpedia.com]

• Dental Caries

  caries Bloom syndrome (p. 234) Roth m u nd Thomson syndrome (p. 238) Hartnup syndrome (p. 250) XP (p. 174) Progeria (p. 156) DNA analysis Blood serum UV irradiated cells with decreased DNA, RNA synthesis Brain computed tomography (CT) calcifications; [cram.com]

  Dental caries is a common finding. Dental rehabilitation of a 14-year-old male with Cockayne’s syndrome is presented. 1. [hindawi.com]

  Criteria required for the diagnosis include poor growth and neurologic abnormality; other very common manifestations include sensorineural hearing loss, cataracts, pigmentary retinopathy, cutaneous photosensitivity, and dental caries. [ncbi.nlm.nih.gov]

  Over the next 4 years he developed marked growth failure, mental retardation, ataxia, sunken eyes, photosensitivity, and dental caries. [nature.com]

• Prognathism

  […] extremities and large hands and feet, kyphosis, cold blue extremities, beak-like nose giving the patient a prematurely old appearance, sparse hair, mental retardation, sensorineural deafness, blindness due to retinal degeneration, coarse voice, deep eyes, prognathism [whonamedit.com]

  Facial abnormalities include an unusually thin nose, sunken eyes and poor eyelid closure, large misshapen ears and prognathism (protruding upper or lower jawbone). Tooth decay is likely to occur due to abnormal placement of the teeth. [alextlc.org]

  A characteristic facies develops, resulting in a thin prominent nose, prognathism, sunken eyes, and a lack of subcutaneous fat. [hindawi.com]

  Neurodevelopmental delay (progressive) · Mental deficiency (progressive) · Unsteady gait · Sunburns easily · Retinopathy and/or cataracts (progressive) · Hearing loss (progressive) · Dental caries · Typical facial appearance: Pinched facies Sunken eyes Beaked nose Prognathism [cockayne-syndrome.net]

  Upper and lower jaw that stick out (prognathism). Hormones Delayed puberty. Fertility issues. Undescended testicles in boys. Neurologic capabilities and development Abnormally tight muscles (spasticity). Decline in intellectual abilities. [my.clevelandclinic.org]

• Hepatomegaly

  Sensorineural hearing loss and hepatomegaly (abnormally enlarged liver) are also common. Those with CS typically have large, cold hands and feet. [alextlc.org]

  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). [statpearls.com]

  Micropenis, cryptorchidism, hepatomegaly, splenomegaly, osteoporosis, hypertension and altered renal function have also been reported in some CS patients (Jones, 1997). A second type of CS (type II or B), has been reported in 20 cases. [scielo.br]

  It also showed hepatomegaly and altered vertebral bodies. The ribs and clavicles were thinned with sclerosis at the margins. These images are characteristic of Cockayne syndrome. Figure 4. Right reticulo-nodular infiltrate and left atelectasis. [elsevier.es]

• Hearing Impairment

  Clinical features included short stature, cachectic senile look, neurological deterioration, photosensitivity, mental retardation, hearing impairment and carious teeth. The phenotype is compatible with a mild variant of type I Cockayne syndrome. [ncbi.nlm.nih.gov]

  It is characterized by growth and developmental delay, vision and hearing impairment, and impairment of the peripheral nervous system function., Type C is a rare form. Its genetic defect is not clear; appears to be a heterogeneous group. [ebi.ac.uk]

  S ; Schulz, A ; Wild, P S ; Beutel, M E ; Blettner, M ; Münzel, T ; Lackner, K J ; Pfeiffer, N cme Hearing Impairment in Old Age Detection, treatment, and associated risks Löhler, J ; Cebulla, M ; Shehata-Dieler, W ; Volkenstein, S ; Völter, C ; Walther [aerzteblatt-international.de]

  Children with Cockayne syndrome experience a form of premature aging, severe neurodegeneration, growth failures, microcephaly, vision and hearing impairments, hypotonia, developmental delays, and an extremely shortened lifespan. [umassmed.edu]

• Macrotia

  […] more ] 0001531 Feeding difficulties Feeding problems Poor feeding [ more ] 0011968 Hyperreflexia Increased reflexes 0001347 Intellectual disability Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ] 0001249 Macrotia [rarediseases.info.nih.gov]

• Small Head

  Cockayne syndrome (CS) is a rare disorder, characterised by small stature, microcephaly (having a small head), developmental delay and premature pathological ageing. [amyandfriends.org]

  Characterised by short stature, facial abnormalities and microcephaly (unusually small head), those with CS will also see their skin age prematurely, experience extreme sensitivity to sunlight and suffer intellectual deficit. [alextlc.org]

• Severe Short Stature

  METHODS: Whole-exome sequencing was employed to study a consanguineous extended family with severe short stature and variable presentations of peripheral neuropathy, lipoatrophy, photosensitivity, webbed neck, and hirsutism. [ncbi.nlm.nih.gov]

  Results Normal Endocrine Biochemistries Associated with Severe Short Stature The GH-IGF-1 axis was initially assessed, since the shared phenotype amongst the affected family members was severe short stature. [karger.com]

• Hyperpigmentation

  […] patient hypersensitive to UV and leads to progressive neurodegeneration; overlap of XPB, XPD, XPG with Cockayne exists in small number of patients Skin Photosensitive eruption with erythema and scale in "butterfly" distribution on face may resolve with hyperpigmentation [cram.com]

  Skin findings include photosensitive eruption with erythema and scale, hyperpigmentation, telangiectasia, and subcutaneous lipoatrophy that results in an aged progeric appearance. There is no cancer proneness [4]. [latunisiemedicale.com]

  Hyperpigmentation, varicose or spider veins (telangiectasia), and serious sensitivity to sunlight are common, even in individuals without XP-CS. Often patients with Cockayne Syndrome will severely burn or blister with very little exposure. [en.wikipedia.org]

  […] outer layer of the brain due to loss of brain cells 0002120 Decreased nerve conduction velocity 0000762 EEG abnormality 0002353 Erythema 0010783 Fine hair Fine hair shaft Fine hair texture Thin hair shaft Thin hair texture [ more ] 0002213 Generalized hyperpigmentation [rarediseases.info.nih.gov]

• Photosensitive Skin Rash

  Dental cavities Tooth cavities Tooth decay [ more ] 0000670 Cutaneous photosensitivity Photosensitive skin Photosensitive skin rashes Photosensitivity Sensitivity to sunlight Skin photosensitivity Sun sensitivity [ more ] 0000992 Deeply set eye Deep [rarediseases.info.nih.gov]

• Dry Eyes

  As a result, they suffer from dryness of the eye. Dry eyes affect vision acuity. Hearing problems are common. These problems are caused by neurons that progressively deteriorate. This hearing deterioration is the same as occurs with normal aging. [mentalhelp.net]

  They may also have cataracts, feeding difficulties in infancy, failure to thrive, hearing loss, cavities, and dry eyes. All of these problems are common in CS. [forgottendiseases.org]

• Corneal Opacity

  The important ophthalmological features are corneal opacity, cataract, optic atrophy, and salt and pepper pigmentary retinopathy. In our cases, the sister had corneal opacity and the brother had optic atrophy. [neurologyindia.com]

  Cataracts and cloudiness of the cornea (corneal opacity) are common. The loss of and damage to nerves of the optic nerve, causing optic atrophy can occur. [en.wikipedia.org]

• Decreased Lacrimation

  Chronic complications of CS observed include tremors, hypertonia, decreased lacrimation, and cutaneous photosensitivity. [jamanetwork.com]

  lacrimation, sensorineural hearing loss, dental caries, short stature, and a characteristic physical appearance of “cachectic dwarfism”.1 Atypical features in our patient include later age of onset of neurological signs, absence of dental caries, and [jmg.bmj.com]

• Loss of Facial Adipose Tissue

  Sunken eyes, loss of facial adipose tissue, slender nose, large ears (Figure 1), narrow palate and dental caries were also noticed. Neurological examination showed ataxia, diffuse hyporreflexia and insensitivity to vibration in the lower limbs. [scielo.br]

• Tremor

  Status of tremors, ability to perform daily tasks, serial physical examinations, and results of handwriting samples. All 3 patients had a clear reduction in tremors and improvements in handwriting and manipulation of utensils and cups. [ncbi.nlm.nih.gov]

  He was prescribed a combination of carbidopa, 25 mg, and levodopa, 100 mg, and took half a tablet each morning, which improved his tremors; the resting tremor improved more than the intention tremor. [jamanetwork.com]

  Due to a tremor phenomenology similar to Holmes tremor [8], programming was adjusted to monopolar stimulation of posteroventral contacts 8 and 0 at a frequency of 75 Hz, a PW of 100 μs, and an amplitude of 1.5 V, with some improvement in tremor control [e-jmd.org]

  November 05, 2019; 93 (19) Video NeuroImages First published November 4, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008449 A 20-year-old woman presented with bilateral upper limb tremor, mild dystonia, and dysphonia (video). [n.neurology.org]

  Tremors, or shakiness, are common. Genetics: This is an autosomal recessive disorder which requires the presence of two mutations to cause disease. Parents are not affected but carry a single copy of the mutation. [disorders.eyes.arizona.edu]

• Abnormal Gait

  According to neurologic examination patients show abnormal gait coupled with increased or decreased muscle tone and reflexes. The abnormal gait is due to contractures of the ankles, knees and hips as well as leg spasticity and ataxia. [symptoma.com]

  gait or inability to walk, lack of coordination ( ataxia ), lack of urination control (incontinence), tremor, abnormal or absent speech, seizures, weak cry/poor feeding (as an infant), muscle wasting (atrophy), and behavioral abnormality Skin issues: [rarediseases.info.nih.gov]

  Increased tone/spasticity, hyper- or hyporeflexia, abnormal gait or inability to walk, ataxia, incontinence, tremor, abnormal or absent speech, seizures, weak cry/poor feeding (as an infant), muscle atrophy, and behavioral abnormality Dermatologic. [ncbi.nlm.nih.gov]

In situations where patients are suspected to have CS, the first step taken by professionals is to establish baseline renal function and deal with possibility of other conditions with the help of routine laboratory tests [8].

Chromosome analysis is the next step taken so as to remove karyotypic abnormalities associated with growth failure. Chromosome breakage studies may come in if Bloom Syndrome is considered in the differential diagnosis [9]. These studies coupled with mutation analysis are very important so as to remove the possibility of Bloom Syndrome or isolated xeroderma pigmentosum.

CT Scan and MRI scans can equally be used to search for white matter irregularities, cerebral atrophy, increased ventricular size and normal pressure hydrocephaly. Radiographs of the skeleton will also show vertebral body and pelvic abnormalities.

Other tests carried out include audiometry to determine sensorineural hearing loss, electroencephalography to look through any seizure activities and electroretinography to see if there are abnormalities in the electric potential of the retina.

Medical care is purely supportive and includes physiotherapy, photoprotection with sunscreens and clothing and hearing aids.

Cockayne syndrome is an autosomal recessive ailment which leads to neurologic dysfunction and growth failure. Patients with this condition die within the adolescent years but it is possible to survive deep into adulthood.

Genetically, the Cockayne Syndrome and subtypes is classified as follows:

Cockayne Syndrome is caused by the mutations in the ERCC6 and ERCC8 genes [2]. These genes aid the repair of damaged DNA using the proteins they make, through the transcription-coupled repair mechanism. When the ERCC8 or ERCC6 gene is altered, DNA damage is not repaired. The accumulation of this damage is what results in the malfunctioning of cells and death of the cells.

According to the office of rare diseases, the Cockayne Syndrome is a rare condition. This means that less than 2 in 100,000 people have any of the CS subtypes. The CS I is panethnic and since the condition is an autosomal recessive disorder, the male to female ratio is 1:1.

Since it is a progressive congenital disorder, clinical symptoms rarely surface until late infancy or early childhood.

With all types of Cockayne Syndrome, aging prematurely is a cardinal feature [3]. The abnormality in growth and development become visible within the first two years of life. When the disease is at its peak, the head circumference, weight and height of the individual will be far below the fifth percentile.

The aging process is illustrated by bent standing posture, sunken eyes, thinning of the hair and skin and all the usual physical appearance of cachectic dwarfism. Additionally, there is an extensive and diffuse demyelination in both the central and peripheral nervous systems. 

Basal ganglia and precapillary calcifications are visible at a very age. Acute neuronal loss in the cerebellum and cerebral cortex is also present. All of these are consistent with the physiological changes associated with aging.

There are no guidelines for prevention of Cockayne syndrome.

Cockayne Syndrome is a congenital autosomal recessive condition that has been categorized as rare. The common characteristics of this condition are stunted growth, under development of the nervous system, photosensitivity (abnormal sunlight sensitivity), progeria (fast paced aging) and early death [1].

The symptoms vary greatly in patients depending on the age at which the first signs appear. CS is part of a group referred to as the “leukodystrophies”. These are conditions which are characterised by the degeneration of white matter.

The disorder is basically a defect in the repair mechanism of DNA.
A couple known to be carriers of a single CS gene mutation has a 25% possibility of giving birth to a child with the Cockayne Syndrome condition. A child can only be affected by the condition if he inherits a mutation in a particular CS gene from the parents (both).

Since the symptoms of the Cockayne Syndrome vary significantly, the range of severity has been established by dividing the condition into three distinct types. They are as follows:

CS I

With this type of CS, the patient shows usual prenatal growth but at around one year of age, the developmental abnormalities begin to surface. Individuals with this CS type have an average lifespan of 10 to 20 years.

CS II

This CS type is known by the abnormalities and growth failure which begin at birth. Postnatal neurological development is poor and in many cases, absent. Individuals with this CS type have an average lifespan of 7 years.

CS III

This CS type sets in later than the previous two. It shows fewer symptoms and there is a slower rate of progression. There is no agreed average lifespan for people with this CS type but some patients live up to 50 years.

In some cases, the patient has a combination of Cockayne Syndrome and Xeroderma Pigmentosium. This is denoted by a variety of changes to the skin. Areas of skin exposed to sunlight may show mild freckling and in more severe cases, skin cancer.

Parents of the patient need to understand that treatment is symptoms-based and supportive. The neurologic and neurosensory abilities of the patient must be optimised in line with medical directions [10]. Such parents must also undergo genetic counselling as having one CS child means that there is a 25% chance of giving birth to another child with the condition.

The individual suffering from Cockayne syndrome must be made to understand the importance of protecting himself from sunlight with sunscreen and commensurate clothing so as to reduce cell damage.

1. Deschavanne P J, Diatloff-Zito C, Macieira-Coelho A, Malaise EP. Unusual sensitivity of two Cockayne's syndrome cell strains to both UV and gamma irradiation. Mutat. Res. 91: 403-406, 1981.
2. Fujimoto WY, Greene M L, Seegmiller JE. Cockayne's syndrome: report of a case with hyperlipoproteinemia, hyperinsulinemia, renal disease, and normal growth hormone. J. Pediat. 75: 881-884, 1969.
3. Hoeijmakers JH. DNA damage, aging, and cancer. N. Engl. J. Med. 2009 361 (15): 1475–85. doi:10.1056/NEJMra0804615
4. Online 'Mendelian Inheritance in Man' (OMIM) Cerebrooculofacioskeletal Syndrome 1; COFS1 -214150
5. Kleijer WJ, Laugel V, Berneburg M, Nardo T, Fawcett H, Gratchev A, Jaspers NG, Sarasin A, Stefanini M, Lehmann AR. Incidence of DNA repair deficiency disorders in western Europe: Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy. DNA Repair (Amst). 2008 May 3;7(5):744-50.
6. Weidenheim KM, Dickson DW, Rapin I. Neuropathology of Cockayne syndrome: Evidence for impaired development, premature aging, and neurodegeneration. Mech Ageing Dev. 2009 Sep;130(9):619-36.
7. Khayat M, Hardouf H, Zlotogora J, Shalev SA. High carriers frequency of an apparently ancient founder mutation p.Tyr322X in the ERCC8 gene responsible for Cockayne syndrome among Christian Arabs in Northern Israel. Am J Med Genet A. Dec 2010;152A(12):3091.
8. Laugel V, Dalloz C, Durand M, et al. Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne syndrome. Hum Mutat. Nov 5 2009.
9. Zhang H, Gao J, Ye J, Gong Z, Gu X. Maternal origin of a de novo microdeletion spanning the ERCC6 gene in a classic form of the Cockayne syndrome. Eur J Med Genet. Jul-Aug 2011;54(4):e389-93.
10. Cunniff C. Prenatal screening and diagnosis for pediatricians. Pediatrics. Sep 2004;114(3):889-94.