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Cohen syndrome(COH1)

MedGen UID:
78539
Concept ID:
C0265223
Congenital Abnormality
Synonyms: COH1; Cutis verticis gyrata, retinitis pigmentosa, and sensorineural deafness; Pepper syndrome
SNOMED CT: Cohen syndrome (56604005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): VPS13B (8q22.2)
 
Monarch Initiative: MONDO:0008999
OMIM®: 216550
Orphanet: ORPHA193

Disease characteristics

Excerpted from the GeneReview: Cohen Syndrome
Cohen syndrome is characterized by failure to thrive in infancy and childhood; truncal obesity in the teen years; early-onset hypotonia and developmental delays; microcephaly developing during the first year of life; moderate to profound psychomotor retardation; progressive retinochoroidal dystrophy and high myopia; neutropenia in many with recurrent infections and aphthous ulcers in some; a cheerful disposition; joint hypermobility; and characteristic facial features. [from GeneReviews]
Authors:
Heng Wang  |  Marni J Falk  |  Christine Wensel, et. al.   view full author information

Additional descriptions

From OMIM
Cohen syndrome is an autosomal recessive multisystem disorder characterized by many clinical features, including facial dysmorphism, microcephaly, truncal obesity, impaired intellectual development, progressive retinopathy, and intermittent congenital neutropenia (summary by Duplomb et al., 2014).  http://www.omim.org/entry/216550
From MedlinePlus Genetics
Cohen syndrome is an inherited disorder that affects many parts of the body and is characterized by developmental delay, intellectual disability, small head size (microcephaly), and weak muscle tone (hypotonia). Other features common in this condition include worsening nearsightedness (myopia), breakdown (degeneration) of the light-sensitive tissue at the back of the eye (retinal dystrophy), an unusually large range of joint movement (hypermobility), and distinctive facial features. These facial features typically include thick hair and eyebrows, long eyelashes, unusually-shaped eyes (down-slanting and wave-shaped), a bulbous nasal tip, a smooth or shortened area between the nose and the upper lip (philtrum), and prominent upper central teeth. The combination of the last two facial features results in an open mouth.\n\nThe features of Cohen syndrome vary widely among affected individuals. Additional signs and symptoms in some individuals with this disorder include low levels of white blood cells (neutropenia), overly friendly behavior, and obesity that develops in late childhood or adolescence. When obesity is present, it typically occurs around the torso, with the arms and legs remaining slender (called truncal obesity). Individuals with Cohen syndrome may also have narrow hands and feet, and slender fingers.  https://medlineplus.gov/genetics/condition/cohen-syndrome

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Cubitus valgus
MedGen UID:
490152
Concept ID:
C0158465
Acquired Abnormality
Abnormal positioning in which the elbows are turned out.
Single transverse palmar crease
MedGen UID:
96108
Concept ID:
C0424731
Finding
The distal and proximal transverse palmar creases are merged into a single transverse palmar crease.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Narrow palm
MedGen UID:
346628
Concept ID:
C1857632
Finding
For children from birth to 4 years of age, the palm width is more than 2 SD below the mean; for children from 4 to 16 years of age the palm width is below the 5th centile; or, the width of the palm appears disproportionately narrow for its length.
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
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.
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).
Childhood-onset truncal obesity
MedGen UID:
348475
Concept ID:
C1859846
Finding
Truncal obesity with onset during childhood, defined as between 2 and 10 years of age.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
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.
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.
Thick corpus callosum
MedGen UID:
371993
Concept ID:
C1835194
Finding
Increased vertical dimension of the corpus callosum. This feature can be visualized by sagittal sections on magnetic resonance tomography imaging of the brain.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Hypoplasia of the maxilla
MedGen UID:
66804
Concept ID:
C0240310
Congenital Abnormality
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Lumbar hyperlordosis
MedGen UID:
263149
Concept ID:
C1184923
Finding
An abnormal accentuation of the inward curvature of the spine in the lumbar region.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The ability of a joint to move beyond its normal range of motion.
Facial hypotonia
MedGen UID:
336889
Concept ID:
C1845251
Finding
Reduced muscle tone of a muscle that is innervated by the facial nerve (the seventh cranial nerve).
Short metatarsal
MedGen UID:
341358
Concept ID:
C1849020
Finding
Diminished length of a metatarsal bone, with resultant proximal displacement of the associated toe.
Thoracic scoliosis
MedGen UID:
387910
Concept ID:
C1857790
Anatomical Abnormality
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Congenital laryngomalacia
MedGen UID:
120500
Concept ID:
C0264303
Anatomical Abnormality
Laryngomalacia is a congenital abnormality of the laryngeal cartilage in which the cartilage is floppy and prolapses over the larynx during inspiration.
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Open mouth
MedGen UID:
116104
Concept ID:
C0240379
Finding
A facial appearance characterized by a permanently or nearly permanently opened mouth.
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Macrodontia of permanent maxillary central incisor
MedGen UID:
371973
Concept ID:
C1835095
Finding
Increased size of the maxillary central secondary incisor tooth.
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Delayed puberty
MedGen UID:
46203
Concept ID:
C0034012
Pathologic Function
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.
Decreased response to growth hormone stimulation test
MedGen UID:
1784655
Concept ID:
C5539399
Finding
Insufficient responses to growth hormone (GH) provocation tests. GH deficiency is defined as a serum peak GH concentration less than 10 ng/mL on provocation with a combination of at least two separate stimulation tests.
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Night blindness
MedGen UID:
10349
Concept ID:
C0028077
Disease or Syndrome
Inability to see well at night or in poor light.
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.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Benign concentric annular macular dystrophy
MedGen UID:
321812
Concept ID:
C1828210
Finding
Retinitis pigmentosa-91 (R91) is characterized by night blindness and constriction of visual fields, with bone-spicule pigmentation, attenuation of retinal vessels, and optic disc pallor on funduscopy. Patients may also experience early macular involvement, with photophobia and reduced visual acuity, and some show a bull's eye pattern of macular atrophy (Olivier et al., 2021).
Bone spicule pigmentation of the retina
MedGen UID:
323029
Concept ID:
C1836926
Finding
Pigment migration into the retina in a bone-spicule configuration (resembling the nucleated cells within the lacuna of bone).
Chorioretinal dystrophy
MedGen UID:
346626
Concept ID:
C1857627
Disease or Syndrome
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.

Term Hierarchy

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

Recent clinical studies

Etiology

Gabrielle PH, Faivre L, Audo I, Zanlonghi X, Dollfus H, Thiadens AAHJ, Zeitz C, Mancini GMS, Perdomo Y, Mohand-Saïd S, Lizé E, Lhussiez V, Nandrot EF, Acar N, Creuzot-Garcher C, Sahel JA, Ansar M, Thauvin-Robinet C, Duplomb L, Da Costa R
Sci Rep 2021 Aug 12;11(1):16412. doi: 10.1038/s41598-021-95743-8. PMID: 34385517Free PMC Article
Limoge F, Faivre L, Gautier T, Petit JM, Gautier E, Masson D, Jego G, El Chehadeh-Djebbar S, Marle N, Carmignac V, Deckert V, Brindisi MC, Edery P, Ghoumid J, Blair E, Lagrost L, Thauvin-Robinet C, Duplomb L
Hum Mol Genet 2015 Dec 1;24(23):6603-13. Epub 2015 Sep 10 doi: 10.1093/hmg/ddv366. PMID: 26358774
Rafiq MA, Leblond CS, Saqib MA, Vincent AK, Ambalavanan A, Khan FS, Ayaz M, Shaheen N, Spiegelman D, Ali G, Amin-ud-Din M, Laurent S, Mahmood H, Christian M, Ali N, Fennell A, Nanjiani Z, Egger G, Caron C, Waqas A, Ayub M, Rasheed S, Forgeot d'Arc B, Johnson A, So J, Brohi MQ, Mottron L, Ansar M, Vincent JB, Xiong L
BMC Med Genet 2015 Jun 25;16:41. doi: 10.1186/s12881-015-0183-0. PMID: 26104215Free PMC Article
Ionita-Laza I, Capanu M, De Rubeis S, McCallum K, Buxbaum JD
PLoS Genet 2014 Dec;10(12):e1004729. Epub 2014 Dec 11 doi: 10.1371/journal.pgen.1004729. PMID: 25502226Free PMC Article
Parri V, Katzaki E, Uliana V, Scionti F, Tita R, Artuso R, Longo I, Boschloo R, Vijzelaar R, Selicorni A, Brancati F, Dallapiccola B, Zelante L, Hamel CP, Sarda P, Lalani SR, Grasso R, Buoni S, Hayek J, Servais L, de Vries BB, Georgoudi N, Nakou S, Petersen MB, Mari F, Renieri A, Ariani F
Eur J Hum Genet 2010 Oct;18(10):1133-40. Epub 2010 May 12 doi: 10.1038/ejhg.2010.59. PMID: 20461111Free PMC Article

Diagnosis

Karimzadeh MR, Omidi F, Sahebalzamani A, Saeidi K
J Mol Neurosci 2021 Dec;71(12):2566-2574. Epub 2021 May 26 doi: 10.1007/s12031-021-01852-4. PMID: 34041686
Momtazmanesh S, Rayzan E, Shahkarami S, Rohlfs M, Klein C, Rezaei N
BMC Med Genet 2020 Jun 30;21(1):140. doi: 10.1186/s12881-020-01075-1. PMID: 32605629Free PMC Article
Nasser F, Kurtenbach A, Biskup S, Weidensee S, Kohl S, Zrenner E
Acta Ophthalmol 2020 May;98(3):e316-e321. Epub 2019 Oct 3 doi: 10.1111/aos.14255. PMID: 31580008
Alipour N, Salehpour S, Tonekaboni SH, Rostami M, Bahari S, Yassaee V, Miryounesi M, Ghafouri-Fard S
J Mol Neurosci 2020 Jan;70(1):21-25. Epub 2019 Aug 23 doi: 10.1007/s12031-019-01394-w. PMID: 31444703
Rejeb I, Jilani H, Elaribi Y, Hizem S, Hila L, Zillahrdt JL, Chelly J, Benjemaa L
BMC Med Genet 2017 Nov 17;18(1):134. doi: 10.1186/s12881-017-0493-5. PMID: 29149870Free PMC Article

Therapy

Sevik MO, Aykut A, Şahin Ö
Ophthalmic Genet 2021 Oct;42(5):619-623. Epub 2021 May 11 doi: 10.1080/13816810.2021.1925928. PMID: 33974487
Selmi C
Clin Rev Allergy Immunol 2014 Aug;47(1):1-5. doi: 10.1007/s12016-014-8441-z. PMID: 25086643
Cokkinos P, Gkouziouta A, Karavolias G, Kariofillis P, Voudris V
Hellenic J Cardiol 2013 Mar-Apr;54(2):143-6. PMID: 23557616
Orbach-Zinger S, Kaufman E, Donchin Y, Perouansky M
Acta Anaesthesiol Scand 2003 Sep;47(8):1047-9. doi: 10.1034/j.1399-6576.2003.00169.x. PMID: 12904202
Seow WK, Bartold PM, Thong YH, Taylor K
Pediatr Dent 1998 Sep-Oct;20(5):350-4. PMID: 9803437

Prognosis

Zorn M, Kühnisch J, Bachmann S, Seifert W
Sci Rep 2022 Jun 11;12(1):9686. doi: 10.1038/s41598-022-13717-w. PMID: 35690661Free PMC Article
Hashmi JA, Fadhli F, Almatrafi A, Afzal S, Ramzan K, Thiele H, Nürnberg P, Basit S
Brain Dev 2020 Sep;42(8):587-593. Epub 2020 May 10 doi: 10.1016/j.braindev.2020.04.010. PMID: 32402540
Yang C, Hou M, Li Y, Sun D, Guo Y, Liu P, Liu Y, Song J, Zhang N, Wei W, Chen Z
Int J Dev Neurosci 2018 Aug;68:83-88. Epub 2018 May 24 doi: 10.1016/j.ijdevneu.2018.05.004. PMID: 29758347
Uyhazi KE, Binenbaum G, Carducci N, Zackai EH, Aleman TS
Ophthalmic Genet 2018 Jun;39(3):399-404. Epub 2018 Apr 10 doi: 10.1080/13816810.2018.1459735. PMID: 29634382
Rejeb I, Jilani H, Elaribi Y, Hizem S, Hila L, Zillahrdt JL, Chelly J, Benjemaa L
BMC Med Genet 2017 Nov 17;18(1):134. doi: 10.1186/s12881-017-0493-5. PMID: 29149870Free PMC Article

Clinical prediction guides

Zorn M, Kühnisch J, Bachmann S, Seifert W
Sci Rep 2022 Jun 11;12(1):9686. doi: 10.1038/s41598-022-13717-w. PMID: 35690661Free PMC Article
Hashmi JA, Fadhli F, Almatrafi A, Afzal S, Ramzan K, Thiele H, Nürnberg P, Basit S
Brain Dev 2020 Sep;42(8):587-593. Epub 2020 May 10 doi: 10.1016/j.braindev.2020.04.010. PMID: 32402540
Koehler K, Schuelke M, Hell AK, Schittkowski M, Huebner A, Brockmann K
Am J Med Genet A 2020 Mar;182(3):570-575. Epub 2019 Dec 11 doi: 10.1002/ajmg.a.61435. PMID: 31825161
Nasser F, Kurtenbach A, Biskup S, Weidensee S, Kohl S, Zrenner E
Acta Ophthalmol 2020 May;98(3):e316-e321. Epub 2019 Oct 3 doi: 10.1111/aos.14255. PMID: 31580008
Duplomb L, Rivière J, Jego G, Da Costa R, Hammann A, Racine J, Schmitt A, Droin N, Capron C, Gougerot-Pocidalo MA, Dubrez L, Aral B, Lafon A, Edery P, Ghoumid J, Blair E, El Chehadeh-Djebbar S, Carmignac V, Thevenon J, Guy J, Girodon F, Bastie JN, Delva L, Faivre L, Thauvin-Robinet C, Solary E
J Mol Med (Berl) 2019 May;97(5):633-645. Epub 2019 Mar 7 doi: 10.1007/s00109-019-01754-4. PMID: 30843084

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