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Cockayne syndrome type 1(CSA)

MedGen UID:
155488
Concept ID:
C0751039
Disease or Syndrome
Synonyms: Cockayne syndrome type 1; Cockayne syndrome type I; Cockayne syndrome classic form; Cockayne syndrome classical; Cockayne syndrome type A; ERCC8-Related Cockayne Syndrome
SNOMED CT: Cockayne syndrome type 1 (890433006); Classical Cockayne syndrome (890433006); Cockayne syndrome type A (890433006)
 
Gene (location): ERCC8 (5q12.1)
 
Monarch Initiative: MONDO:0019569
OMIM®: 216400
Orphanet: ORPHA90321

Disease characteristics

Excerpted from the GeneReview: Cockayne Syndrome
Cockayne syndrome (referred to as CS in this GeneReview) spans a continuous phenotypic spectrum that includes: CS type I, the "classic" or "moderate" form; CS type II, a more severe form with symptoms present at birth; this form overlaps with cerebrooculofacioskeletal (COFS) syndrome; CS type III, a milder and later-onset form; COFS syndrome, a fetal form of CS. CS type I is characterized by normal prenatal growth with the onset of growth and developmental abnormalities in the first two years. By the time the disease has become fully manifest, height, weight, and head circumference are far below the fifth percentile. Progressive impairment of vision, hearing, and central and peripheral nervous system function leads to severe disability; death typically occurs in the first or second decade. CS type II is characterized by growth failure at birth, with little or no postnatal neurologic development. Congenital cataracts or other structural anomalies of the eye may be present. Affected children have early postnatal contractures of the spine (kyphosis, scoliosis) and joints. Death usually occurs by age five years. CS type III is a phenotype in which major clinical features associated with CS only become apparent after age two years; growth and/or cognition exceeds the expectations for CS type I. COFS syndrome is characterized by very severe prenatal developmental anomalies (arthrogryposis and microphthalmia). [from GeneReviews]
Authors:
Vincent Laugel   view full author information

Additional description

From OMIM
Cockayne syndrome is characterized by abnormal and slow growth and development that becomes evident within the first few years after birth. 'Cachectic dwarfism' describes the outward appearance of afflicted individuals. Other features include cutaneous photosensitivity, thin, dry hair, a progeroid appearance, progressive pigmentary retinopathy, sensorineural hearing loss, dental caries, and a characteristic stance in the ambulatory patient. Patients often show disproportionately long limbs with large hands and feet, and flexion contractures of joints are usual skeletal features. Knee contractures result in a 'horse-riding stance.' There is delayed neural development and severe progressive neurologic degeneration resulting in mental retardation. The mean age at death in reported cases is 12.5 years, although a few affected individuals have lived into their late teens or twenties. Remarkably, in striking contrast with xeroderma pigmentosum, patients with CS have no significant increase in skin cancer or infection (Nance and Berry, 1992). Lowry (1982) noted that there is an early-onset form of Cockayne syndrome in which patients may show abnormalities at birth and have a shorter survival. Lowry (1982) thus suggested that CS could be divided clinically into the more common type I, with classic CS symptoms that manifest within the first few years or life, and the less common type II, with more severe symptoms that manifest prenatally. Mallery et al. (1998) found no correlation between genotype and phenotype among 16 patients with CS of varying severities, and concluded that clinical differences were based on other genetic backgrounds or the intrauterine environment. Genetic Heterogeneity of Cockayne Syndrome Cockayne syndrome is a genetically heterogeneous disorder, and certain types show some overlap with certain forms of xeroderma pigmentosum (XP), another disorder caused by defective DNA repair. See also Cockayne syndrome B (133540), caused by mutation in the ERCC6 gene (609413) on chromosome 10q11; XPG/CS (see 278780), caused by mutation in the ERCC5 gene (133530) on chromosome 13q33; XPB/CS (see 610651), caused by mutation in the ERCC3 gene (133510) on chromosome 2q21; and XPF/CS (see 278760), caused by mutation in the ERCC4 gene (133520) on chromosome 16p13. Rapin et al. (2000) reviewed the clinical, pathologic, and molecular features of Cockayne syndrome, xeroderma pigmentosum, and the XP-CS complex.  http://www.omim.org/entry/216400

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Proteinuria
MedGen UID:
10976
Concept ID:
C0033687
Finding
Increased levels of protein in the urine.
Irregular menstruation
MedGen UID:
56379
Concept ID:
C0156404
Finding
Abnormally high variation in the amount of time between periods.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Ivory epiphyses of the phalanges of the hand
MedGen UID:
346631
Concept ID:
C1857651
Finding
Sclerosis of the epiphyses of the phalanges of the fingers, leading to an increased degree of radiopacity (white or ivory appearance) in X-rays.
Cardiac arrhythmia
MedGen UID:
2039
Concept ID:
C0003811
Finding
Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.
Hypertensive disorder
MedGen UID:
6969
Concept ID:
C0020538
Disease or Syndrome
The presence of chronic increased pressure in the systemic arterial system.
Persistent left superior vena cava
MedGen UID:
75586
Concept ID:
C0265931
Congenital Abnormality
A rare congenital vascular anomaly that results when the left superior cardinal vein caudal to the innominate vein fails to regress.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Severe postnatal growth retardation
MedGen UID:
347510
Concept ID:
C1857641
Finding
Severely slow or limited growth after birth, being four standard deviations or more below age- and sex-related norms.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or external ear.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Normal pressure hydrocephalus
MedGen UID:
42526
Concept ID:
C0020258
Disease or Syndrome
Normal-pressure hydrocephalus-1 (HYDNP1) is an autosomal dominant neurologic disorder characterized by the clinical triad of slowly progressive gait instability, urinary incontinence, and cognitive decline associated with ventricular enlargement on brain imaging with normal pressure of the cerebrospinal fluid (CSF). The onset of symptoms is usually in late adulthood; the symptoms are responsive to shunting. The disorder has been associated with recurrent respiratory infections and possible infertility issues, but the latter has not been confirmed (summary by Takahashi et al., 2011 and Morimoto et al., 2019).
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Polyneuropathy
MedGen UID:
57502
Concept ID:
C0152025
Disease or Syndrome
A generalized disorder of peripheral nerves.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Abnormal auditory evoked potentials
MedGen UID:
141758
Concept ID:
C0522216
Finding
An abnormality of the auditory evoked potentials, which are used to trace the signal generated by a sound, from the cochlear nerve, through the lateral lemniscus, to the medial geniculate nucleus, and to the cortex.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk. In general, this can refer to neurological diseases but also fractures or other sources of pain that is triggered upon walking. However, in the current context gait disturbance refers to difficulty walking on the basis of a neurological or muscular disease.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Patchy demyelination of subcortical white matter
MedGen UID:
341813
Concept ID:
C1857638
Finding
Patchy loss of myelin from nerve fibers in the central nervous system.
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Peripheral dysmyelination
MedGen UID:
871139
Concept ID:
C4025610
Finding
Defective structure and function of myelin sheaths. Dysmyelination is distinguished from demyleination where there is destruction or damage of previously normal myelination.
Abnormal peripheral myelination
MedGen UID:
871174
Concept ID:
C4025648
Anatomical Abnormality
An abnormality of the myelination of motor and sensory peripheral nerves. These are axons for motor nerves and dendrites for sensory nerves in the strict anatomic sense.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Hip contracture
MedGen UID:
140815
Concept ID:
C0409354
Acquired Abnormality
Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the hip joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.
Basal ganglia calcification
MedGen UID:
234651
Concept ID:
C1389280
Pathologic Function
The presence of calcium deposition affecting one or more structures of the basal ganglia.
Loss of facial adipose tissue
MedGen UID:
325251
Concept ID:
C1837767
Finding
Loss of normal subcutaneous fat tissue in the face.
Square pelvis bone
MedGen UID:
337928
Concept ID:
C1849953
Anatomical Abnormality
An abnormally squared appearance of the bony pelvis, a normally rounded or basin-shaped structure.
Limitation of joint mobility
MedGen UID:
341696
Concept ID:
C1857108
Finding
A reduction in the freedom of movement of one or more joints.
Reduced subcutaneous adipose tissue
MedGen UID:
387876
Concept ID:
C1857657
Finding
A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.
Thickened calvaria
MedGen UID:
346823
Concept ID:
C1858452
Finding
The presence of an abnormally thick calvaria.
Hypoplastic iliac wing
MedGen UID:
351279
Concept ID:
C1865027
Anatomical Abnormality
Underdevelopment of the ilium ala.
Hypoplastic pelvis
MedGen UID:
760700
Concept ID:
C3536734
Anatomical Abnormality
Underdevelopment of the bony pelvis.
Atypical scarring of skin
MedGen UID:
867415
Concept ID:
C4021786
Pathologic Function
Atypically scarred skin .
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Thymic hormone decreased
MedGen UID:
341815
Concept ID:
C1857652
Finding
A reduction in the level of thymic horomone.
Carious teeth
MedGen UID:
8288
Concept ID:
C0011334
Disease or Syndrome
Caries is a multifactorial bacterial infection affecting the structure of the tooth. This term has been used to describe the presence of more than expected dental caries.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
Hypoplasia of teeth
MedGen UID:
852449
Concept ID:
C0235357
Congenital Abnormality
Developmental hypoplasia of teeth.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Delayed eruption of primary teeth
MedGen UID:
341477
Concept ID:
C1849538
Finding
Delayed tooth eruption affecting the primary dentition.
Slender nose
MedGen UID:
347514
Concept ID:
C1857645
Finding
Anhidrosis
MedGen UID:
1550
Concept ID:
C0003028
Disease or Syndrome
Inability to sweat.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Dry hair
MedGen UID:
75809
Concept ID:
C0277960
Finding
Hair that lacks the lustre (shine or gleam) of normal hair.
Cutaneous photosensitivity
MedGen UID:
87601
Concept ID:
C0349506
Pathologic Function
An increased sensitivity of the skin to light. Photosensitivity may result in a rash upon exposure to the sun (which is known as photodermatosis). Photosensitivity can be diagnosed by phototests in which light is shone on small areas of skin.
Abnormality of skin pigmentation
MedGen UID:
224697
Concept ID:
C1260926
Finding
An abnormality of the pigmentation of the skin.
Prematurely aged appearance
MedGen UID:
346633
Concept ID:
C1857656
Finding
Progeroid facial appearance
MedGen UID:
341830
Concept ID:
C1857710
Finding
A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.
Sparse hair
MedGen UID:
1790211
Concept ID:
C5551005
Finding
Reduced density of hairs.
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Hypermetropia
MedGen UID:
43780
Concept ID:
C0020490
Disease or Syndrome
An abnormality of refraction characterized by the ability to see objects in the distance clearly, while objects nearby appear blurry.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Decreased lacrimation
MedGen UID:
116004
Concept ID:
C0235857
Finding
Abnormally decreased lacrimation, that is, reduced ability to produce tears.
Deeply set eye
MedGen UID:
473112
Concept ID:
C0423224
Finding
An eye that is more deeply recessed into the plane of the face than is typical.
Opacification of the corneal stroma
MedGen UID:
602191
Concept ID:
C0423250
Finding
Reduced transparency of the stroma of cornea.
Retinal atrophy
MedGen UID:
101075
Concept ID:
C0521694
Disease or Syndrome
Well-demarcated area(s) of partial or complete depigmentation in the fundus, reflecting atrophy of the retinal pigment epithelium with associated retinal photoreceptor loss.
Abnormality of visual evoked potentials
MedGen UID:
105509
Concept ID:
C0522214
Finding
An anomaly of visually evoked potentials (VEP), which are electrical potentials, initiated by brief visual stimuli, which are recorded from the scalp overlying the visual cortex.
Retinal pigment epithelial mottling
MedGen UID:
347513
Concept ID:
C1857644
Finding
Mottling (spots or blotches with different shades) of the retinal pigment epithelium, i.e., localized or generalized fundal pigment granularity associated with processes at the level of the retinal pigment epithelium.
Pigmentary retinopathy
MedGen UID:
1643295
Concept ID:
C4551715
Disease or Syndrome
An abnormality of the retina characterized by pigment deposition. It is typically associated with migration and proliferation of macrophages or retinal pigment epithelial cells into the retina; melanin from these cells causes the pigmentary changes. Pigmentary retinopathy is a common final pathway of many retinal conditions and is often associated with visual loss.
Increased cellular sensitivity to UV light
MedGen UID:
346648
Concept ID:
C1857707
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Cockayne syndrome type 1 in Orphanet.

Professional guidelines

PubMed

Giambona A, Vinciguerra M, Leto F, Cassarà F, Cucinella G, Cigna V, Orlandi E, Piccione M, Picciotto F, Maggio A
J Obstet Gynaecol 2022 Jul;42(5):1524-1531. Epub 2022 Jan 10 doi: 10.1080/01443615.2021.2014429. PMID: 35006018
Kraemer KH, Patronas NJ, Schiffmann R, Brooks BP, Tamura D, DiGiovanna JJ
Neuroscience 2007 Apr 14;145(4):1388-96. Epub 2007 Feb 1 doi: 10.1016/j.neuroscience.2006.12.020. PMID: 17276014Free PMC Article
Rosell R, Taron M, Alberola V, Massuti B, Felip E
Lung Cancer 2003 Aug;41 Suppl 1:S97-102. doi: 10.1016/s0169-5002(03)00151-x. PMID: 12867068

Recent clinical studies

Diagnosis

Baer S, Tuzin N, Kang PB, Mohammed S, Kubota M, van Ierland Y, Busa T, Rossi M, Morel G, Michot C, Baujat G, Durand M, Obringer C, Le May N, Calmels N, Laugel V
Eur J Med Genet 2021 Jan;64(1):104105. Epub 2020 Nov 20 doi: 10.1016/j.ejmg.2020.104105. PMID: 33227433

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