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Cerebrooculofacioskeletal syndrome 1(COFS1)

MedGen UID:
66320
Concept ID:
C0220722
Disease or Syndrome
Synonyms: Cerebro-oculo-facio-skeletal syndrome 1; COFS1
 
Gene (location): ERCC6 (10q11.23)
 
Monarch Initiative: MONDO:0008955
OMIM®: 214150

Definition

Cerebrooculofacioskeletal syndrome is an autosomal recessive progressive neurodegenerative disorder characterized by microcephaly, congenital cataracts, severe mental retardation, facial dysmorphism, and arthrogryposis (summary by Jaakkola et al., 2010). Genetic Heterogeneity of Cerebrooculofacioskeletal Syndrome See also COFS2 (610756), caused by mutation in the ERCC2 gene (126340); COFS3 (616570), caused by mutation in the ERCC5 gene (133530); and COFS4 (610758), caused by mutation in the ERCC1 gene (126380). [from OMIM]

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).
Coxa valga
MedGen UID:
116080
Concept ID:
C0239137
Finding
Coxa valga is a deformity of the hip in which the angle between the femoral shaft and the femoral neck is increased compared to age-adjusted values (about 150 degrees in newborns gradually reducing to 120-130 degrees in adults).
Congenital vertical talus
MedGen UID:
66821
Concept ID:
C0240912
Congenital Abnormality
Congenital vertical talus (CVT), also known as 'rocker-bottom foot' deformity, is a dislocation of the talonavicular joint characterized by vertical orientation of the talus with a rigid dorsal dislocation of the navicular, equinus deformity of the calcaneus, abduction deformity of the forefoot, and contracture of the soft tissues of the hind- and mid-foot. This condition is usually associated with multiple other congenital deformities and only rarely is an isolated deformity with familial occurrence (summary by Levinsohn et al., 2004). The condition is transmitted in an autosomal dominant pattern of inheritance, and sometimes shows incomplete penetrance and variable expressivity. There may be a broad spectrum of deformities, including flatfoot, talipes equinovarus (TEV or clubfoot), cavus foot, metatarsus adductus, and even hypoplasia of the tibia (summary by Dobbs et al., 2006).
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
Second metatarsal posteriorly placed
MedGen UID:
347105
Concept ID:
C1859224
Finding
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
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.
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.
Ear malformation
MedGen UID:
75618
Concept ID:
C0266589
Congenital Abnormality
An abnormality of the ear.
Gliosis
MedGen UID:
4899
Concept ID:
C0017639
Pathologic Function
Gliosis is the focal proliferation of glial cells in the central nervous system.
Neurodegeneration
MedGen UID:
17999
Concept ID:
C0027746
Cell or Molecular Dysfunction
Progressive loss of neural cells and tissue.
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.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
CNS demyelination
MedGen UID:
137898
Concept ID:
C0338474
Disease or Syndrome
A loss of myelin from nerve fibers in the central nervous system.
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.
Diffuse cerebral atrophy
MedGen UID:
108958
Concept ID:
C0598275
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
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.
Delayed myelination
MedGen UID:
224820
Concept ID:
C1277241
Finding
Delayed myelination.
Progressive neurologic deterioration
MedGen UID:
381506
Concept ID:
C1854838
Finding
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Brain atrophy
MedGen UID:
1643639
Concept ID:
C4551584
Disease or Syndrome
Partial or complete wasting (loss) of brain tissue that was once present.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Joint contracture of the hand
MedGen UID:
56382
Concept ID:
C0158113
Finding
Contractures of one ore more joints of the hands meaning chronic loss of joint motion due to structural changes in non-bony tissue.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Elbow flexion contracture
MedGen UID:
98367
Concept ID:
C0409338
Acquired Abnormality
An elbow contracture that limits the ability of the elbow joint to be extended (straightened), meaning that the elbow is fixed in an flexed (bent) position.
Kyphoscoliosis
MedGen UID:
154361
Concept ID:
C0575158
Anatomical Abnormality
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
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.
Axial hypotonia
MedGen UID:
342959
Concept ID:
C1853743
Finding
Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Dehydration
MedGen UID:
8273
Concept ID:
C0011175
Disease or Syndrome
A condition resulting from the excessive loss of water from the body. It is usually caused by severe diarrhea, vomiting or diaphoresis.
Insulin resistance
MedGen UID:
43904
Concept ID:
C0021655
Pathologic Function
Increased resistance towards insulin, that is, diminished effectiveness of insulin in reducing blood glucose levels.
Metabolic acidosis
MedGen UID:
65117
Concept ID:
C0220981
Pathologic Function
Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Congenital Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
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.
Delayed eruption of teeth
MedGen UID:
68678
Concept ID:
C0239174
Finding
Delayed tooth eruption, which can be defined as tooth eruption more than 2 SD beyond the mean eruption age.
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.
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips).
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Sloping forehead
MedGen UID:
346640
Concept ID:
C1857679
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Hirsutism
MedGen UID:
42461
Concept ID:
C0019572
Disease or Syndrome
Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).
Deep longitudinal plantar crease
MedGen UID:
347104
Concept ID:
C1859223
Finding
Narrow, paramedian longitudinal depressions in the plantar skin of the forefoot.
Wide intermamillary distance
MedGen UID:
473489
Concept ID:
C1827524
Finding
A larger than usual distance between the left and right nipple.
Microphthalmia
MedGen UID:
10033
Concept ID:
C0026010
Congenital Abnormality
Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.\n\nPeople with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.\n\nPeople with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.\n\nBetween one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.
Miosis
MedGen UID:
6409
Concept ID:
C0026205
Disease or Syndrome
Abnormal (non-physiological) constriction of the pupil.
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.
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.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCerebrooculofacioskeletal syndrome 1

Professional guidelines

PubMed

Sirchia F, Fantasia I, Feresin A, Giorgio E, Faletra F, Mordeglia D, Barbieri M, Guida V, De Luca A, Stampalija T
BMC Med Genomics 2021 Mar 25;14(1):89. doi: 10.1186/s12920-021-00939-6. PMID: 33766032Free PMC Article

Recent clinical studies

Etiology

Mondal R, Shanmughan A, Murugeswari A, Shanmugaraju S
Chem Commun (Camb) 2023 Sep 26;59(77):11456-11468. doi: 10.1039/d3cc03125j. PMID: 37674461
Sirchia F, Fantasia I, Feresin A, Giorgio E, Faletra F, Mordeglia D, Barbieri M, Guida V, De Luca A, Stampalija T
BMC Med Genomics 2021 Mar 25;14(1):89. doi: 10.1186/s12920-021-00939-6. PMID: 33766032Free PMC Article
Ferri D, Orioli D, Botta E
Clin Genet 2020 Jan;97(1):12-24. Epub 2019 Apr 22 doi: 10.1111/cge.13545. PMID: 30919937
Yew YW, Giordano CN, Spivak G, Lim HW
J Am Acad Dermatol 2016 Nov;75(5):873-882. doi: 10.1016/j.jaad.2016.03.044. PMID: 27745642
Frouin E, Laugel V, Durand M, Dollfus H, Lipsker D
JAMA Dermatol 2013 Dec;149(12):1414-8. doi: 10.1001/jamadermatol.2013.6683. PMID: 24154677

Diagnosis

Sirchia F, Fantasia I, Feresin A, Giorgio E, Faletra F, Mordeglia D, Barbieri M, Guida V, De Luca A, Stampalija T
BMC Med Genomics 2021 Mar 25;14(1):89. doi: 10.1186/s12920-021-00939-6. PMID: 33766032Free PMC Article
Le Van Quyen P, Calmels N, Bonnière M, Chartier S, Razavi F, Chelly J, El Chehadeh S, Baer S, Boutaud L, Bacrot S, Obringer C, Favre R, Attié-Bitach T, Laugel V, Antal MC
Am J Med Genet A 2020 May;182(5):1236-1242. Epub 2020 Feb 13 doi: 10.1002/ajmg.a.61520. PMID: 32052936
Ferri D, Orioli D, Botta E
Clin Genet 2020 Jan;97(1):12-24. Epub 2019 Apr 22 doi: 10.1111/cge.13545. PMID: 30919937
Yew YW, Giordano CN, Spivak G, Lim HW
J Am Acad Dermatol 2016 Nov;75(5):873-882. doi: 10.1016/j.jaad.2016.03.044. PMID: 27745642
Hosseini M, Ezzedine K, Taieb A, Rezvani HR
J Invest Dermatol 2015 Feb;135(2):341-351. Epub 2014 Oct 9 doi: 10.1038/jid.2014.365. PMID: 25296907

Therapy

Yew YW, Giordano CN, Spivak G, Lim HW
J Am Acad Dermatol 2016 Nov;75(5):873-882. doi: 10.1016/j.jaad.2016.03.044. PMID: 27745642
Hosseini M, Ezzedine K, Taieb A, Rezvani HR
J Invest Dermatol 2015 Feb;135(2):341-351. Epub 2014 Oct 9 doi: 10.1038/jid.2014.365. PMID: 25296907
Frouin E, Laugel V, Durand M, Dollfus H, Lipsker D
JAMA Dermatol 2013 Dec;149(12):1414-8. doi: 10.1001/jamadermatol.2013.6683. PMID: 24154677

Prognosis

Reunert J, van den Heuvel A, Rust S, Marquardt T
Am J Med Genet A 2021 Mar;185(3):930-936. Epub 2020 Dec 27 doi: 10.1002/ajmg.a.62048. PMID: 33369099
Panigrahi I, Shankar Prasad BA, Kaur H, Kalra J
Am J Med Genet A 2021 Feb;185(2):631-635. Epub 2020 Nov 21 doi: 10.1002/ajmg.a.61979. PMID: 33219753

Clinical prediction guides

Panigrahi I, Shankar Prasad BA, Kaur H, Kalra J
Am J Med Genet A 2021 Feb;185(2):631-635. Epub 2020 Nov 21 doi: 10.1002/ajmg.a.61979. PMID: 33219753
Frouin E, Laugel V, Durand M, Dollfus H, Lipsker D
JAMA Dermatol 2013 Dec;149(12):1414-8. doi: 10.1001/jamadermatol.2013.6683. PMID: 24154677

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