Rare Pulmonology News

Disease Profile

Cockayne syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

All ages

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ICD-10

Q87.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Cockayne's syndrome; Dwarfism-retinal atrophy-deafness syndrome; Progeria-like syndrome;

Categories

Congenital and Genetic Diseases

Summary

Cockayne syndrome is a rare disease which causes short stature, premature aging (progeria), severe photosensitivity, and moderate to severe learning delay.[1] This syndrome also includes failure to thrive in the newborn, very small head (microcephaly), and impaired nervous system development. Other symptoms may include hearing loss, tooth decay, vision problems, and bone abnormalities.[2] There are three subtypes according to the severity of the disease and the onset of the symptoms:[2][3]

Cockayne syndrome is caused by mutations in either the ERCC8 (CSA) or ERCC6 (CSB) genes. Inheritance is autosomal recessive.[2] Type 2 is the most severe and affected people usually do not survive past childhood. Those with type 3 live into middle adulthood.[1] There is no cure yet. Treatment is supportive and may include educational programs for developmental delay, physical therapy, gastrostomy tube placement as needed; medications for spasticity and tremor as needed; use of sunscreens and sunglasses; treatment of hearing loss and cataracts; and other forms of treatment, as needed.[3]

Symptoms

The signs and symptoms of Cockayne syndrome are usually apparent from infancy and worsen over time.[3]

Cockayne Type I
Babies look normal at birth, but symptoms develop within the first two years.

More common signs and symptoms:

  • An smaller than normal sized head (microcephaly)
  • Failure to gain weight and grow at the expected rate (failure to thrive) leading to very short stature, and delayed development
  • 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. 
  • Developmental delay
  • Progressive impairment of vision, hearing, and central and peripheral nervous system function leading to severe disability
  • Severe teeth cavities (in up to 86% of individuals)

Symptoms observed in about 10% of the cases:

  • Neurological issues: Increased tone/spasticity, increased reflexes or decreased reflexes (hyperor hyporeflexia), abnormal 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: Lack of sweating (anhidrosis) and facial rash
  • Eye and vision issues: Hollow eyes (enophthalmos), pigmentary retinopathy (60%-100%), cataracts (15%-36%), optic atrophy, farsightedness, decreased or absent tears, strabismus, nystagmus, photophobia, and very small eyes (microphthalmia)
  • Teeth issues: Absent or very small teeth, delayed eruption of deciduous teeth, and malocclusion
  • Kidney issues: Abnormal kidney function and abnormalities
  • Hormonal issues: Undescended testes, delayed/absent sexual maturation
  • Fertility issues: People with classic or severe CS (types I or II) cannot reproduce 
  • Other: Enlargement of liver or spleen

Cockayne Type II 
This is the most severe subtype.

Symptoms may include:

  • Severe growth failure at birth
  • Severe
  • Severe neurologic development
  • Congenital cataracts or other eye anomalies are present in 30% of the cases
  • Joint contractures present at birth (congenital) or early postnatal contractures of the spine (kyphosis, scoliosis) and joints

Cockayne Type III
Similar to CS type I but milder.

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cachexia
Wasting syndrome
0004326
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral dysmyelination
0007266
Mental deterioration
Cognitive decline
Cognitive decline, progressive
Intellectual deterioration
Progressive cognitive decline

[ more ]

0001268
Pigmentary retinopathy
0000580
Postnatal growth retardation
Growth delay as children
0008897
Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

0000253
Progressive sensorineural hearing impairment
0000408
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
30%-79% of people have these symptoms
Basal ganglia calcification
0002135
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Cerebral atrophy
Degeneration of cerebrum
0002059
Congenital contracture
0002803
Contractures of the large joints
0005781
Cutaneous photosensitivity
Photosensitive skin
Photosensitive skin rashes
Photosensitivity
Sensitivity to sunlight
Skin photosensitivity
Sun sensitivity

[ more ]

0000992
Decreased nerve conduction velocity
0000762
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye

[ more ]

0000490
Demyelinating peripheral neuropathy
0007108
Dense calcifications in the cerebellar dentate nucleus
0002461
Dry hair
0011359
Fine hair
Fine hair shaft
Fine hair texture
Thin hair shaft
Thin hair texture

[ more ]

0002213
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Gliosis
0002171
Global developmental delay
0001263
High-frequency sensorineural hearing impairment
0001757
Hypoplasia of dental enamel
Underdeveloped teeth enamel
0006297
Patchy demyelination of subcortical white matter
0002545
Premature skin wrinkling
0100678
Progressive gait ataxia
0007240
Progressive visual loss
Progressive loss of vision
Progressive vision loss
Progressive visual impairment
Slowly progressive visual loss
Vision loss, progressive
Visual loss, progressive

[ more ]

0000529
Reduced subcutaneous adipose tissue
Reduced fat tissue below the skin
0003758
Retinal dystrophy
Breakdown of light-sensitive cells in back of eye
0000556
Seizure
0001250
Sensorimotor neuropathy
Nerve damage causing decreased feeling and movement
0007141
Sensory impairment
0003474
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Subcortical white matter calcifications
0007346
5%-29% of people have these symptoms
Abnormal electroretinogram
0000512
Abnormality of dental morphology
Abnormality of dental shape
Abnormally shaped teeth
Deformity of teeth
Dental deformity
Dental malformations
Malformed teeth
Misshapen teeth
Misshapened teeth

[ more ]

0006482
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Absence of pubertal development
0008197
Alacrima
Absence of tears in the eyes
Absent tear secretion

[ more ]

0000522
Anhidrosis
Lack of sweating
Sweating dysfunction

[ more ]

0000970
Areflexia
Absent tendon reflexes
0001284
Atherosclerosis
Narrowing and hardening of arteries
0002621
Band keratopathy
0000585
Congenital microcephaly
0011451
Convex nasal ridge
Beaked nose
Beaklike protrusion
Hooked nose
Polly beak nasal deformity

[ more ]

0000444
Corneal ulceration

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis mainly includes mitochondrial diseases that may show similar clinical features to those seen in CS.
Visit the Orphanet disease page for more information.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

    In-Depth Information

    • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
    • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
      Cockayne syndrome
      Genetics of Cockayne Syndrome
    • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
    • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

      References

      1. Cockayne Syndrome Brochure. Share & Care Cockayne Syndrome Network. https://cockaynesyndrome.org/about-cs/.
      2. Genetics Home Reference. Cockayne Syndrome. 2016; https://ghr.nlm.nih.gov/condition/cockayne-syndrome.
      3. Laugel V. Cockayne Syndrome. Gene Reviews. June 14, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1342/.

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