Monogenic hearing loss
Gene: COL2A1
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 1:19 p.m. | Last Modified: 3 Mar 2022, 1:19 p.m.
Panel Version: 2.221
Comment on list classification: Upgrading from red to amber. Should be reviewed by the GMS as to whether it is appropriate to make green. Hearing loss is less predominant in individuals with variants in this gene than in some other Stickler syndrome genes, however if hearing loss is picked up and Stickler syndrome is identified early then eye related symptoms may be treatable.Created: 20 Sep 2020, 8:02 a.m. | Last Modified: 7 Oct 2020, 6:05 p.m.
Panel Version: 2.94
Associated with Stickler syndrome, type I #108300 (AD) in OMIM.
PMID: 23110709 - Acke et al 2012 - review the literature to give an overview of hearing loss in Stickler syndrome, correlated with the genotype. 313 patients from 102 families were reviewed. Hearing loss was found in 62.9%, mostly mild to moderate when reported. Mutations in COL11A1 (82.5%) and COL11A2 (94.1%) seem to be more frequently associated with hearing impairment than mutations in COL2A1 (52.2%).
PMID: 27408751 - Kondo et al 2016 - report 21 cases (some familial, most sporadic) with COL2A1 variants. 4/21 (20%) showed hearing loss.
PMID: 20179744 - Hoornaert et al 2010 - identified 77 different heterozygous COL2A1 mutations in 100 affected individuals out of a group of 188 individuals referred with a potential diagnosis of Stickler syndrome. 30% of COL2A1-variant positive patients had sensorineural hearing loss. However, over a higher percentage (50%) of patients without a COL2A1 mutation have sensorineural hearing loss.Created: 15 Sep 2020, 8:06 p.m. | Last Modified: 24 Sep 2020, 6:46 p.m.
Panel Version: 2.94
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Stickler syndrome, type I, 108300
Publications
Deafness is a reported feature of Stickler syndrome, including when caused by variants in this gene. Stickler syndrome can sometimes be difficult to diagnose clinically; early diagnosis has the potential to alter visual outcomes.Created: 29 Jan 2020, 12:27 a.m. | Last Modified: 29 Jan 2020, 12:27 a.m.
Panel Version: 2.4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Stickler syndrome, type I, MIM108300
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
#108300:Stickler syndrome, type I[Normal height; Marfanoid habitus; Flat midface; Sensorineural hearing lossOccasional conductive hearing loss; MyopiaRetinal detachmentBlindnessOccasional cataractsGlaucomaMembranous (type I) vitreous phenotype; Anteverted naresDepressed nasal bridge; Cleft palatePierre-Robin sequence; Mitral valve prolapse; Pectus excavatum; Mild spondyloepiphyseal dysplasia; Platyspondyly with anterior wedgingScoliosisKyphosis; Flat, irregular femoral epiphysesArachnodactylyArthropathy; Caused by mutation in the collagen II, alpha-1 polypeptide gene (COL2A1,)]; #132450:Epiphyseal dysplasia, multiple, with myopia and deafness[Short stature; Round faceFlat face; Deafness, conductive; Myopia, progressive, early onsetRetinal thinningAsteroid hyalosisCataracts, crenated; Snub nose; Small mouth; Epiphyseal dysplasia; Shortened vertebral bodies, mild; Coxa valga deformity; Flattened epiphyses around knee jointGenu valgus; BrachydactylyShort phalanges]; #150600:Legg-Calve-Perthes disease[Painful limp; Legg-Calve-Perthes disease; Short stature; Onset 6-9 years; More severe in females; Necrosis of capital femoral epiphysis; Delayed bone age]; #151210:Platyspondylic skeletal dysplasia, Torrance type[Dwarfism, neonatal short-limbed; Macrocephaly; Coarse facies; Short neck; Narrow chest; Short, thin ribs; Protuberant abdomen; Luton type - hypercellular resting cartilage, normal and large cells, normal column formation, focal degenerating chondrocyte incorporation and focal disorganizationTorrance type - Hypercellular resting cartilage, large cells, normal growth plate; Decreased cranial base ossification; Platyspondyly, extremeDisc-like vertebral bodies; Hypoplastic, wide sacrosciatic notchesFlat acetabular roof; Severe limb shorteningShort, tubular long bonesMetaphyseal cuppingHypoplastic iliaHypoplastic ischiaHypoplastic pubis]; #156550:Kniest dysplasia[Final adult height 106-145cmShort stature, disproportionate (short trunk); Flat midfaceRound face; Conductive hearing lossFrequent otitis media; MyopiaRetinal detachmentCataractsProminent eyes; Low nasal bridge; Cleft palate; Short neck; TracheomalaciaRespiratory distress; Inguinal herniasUmbilical hernias; PlatyspondylyLumbar kyphoscoliosisCoronal vertebral cleftsOccipitoatlantal instability; Flexion contractures of hipsHypoplastic pelvic bonesHip dislocationCoxa vara; Short, dumbbell appearance of long bonesSplayed epiphyses and metaphysesDelayed epiphyseal ossification (early)Megaepiphyses (late)Narrowing of joint spacesEnlarged jointsLimited joint mobilityPainful joints; Flattened, squared-off epiphyses of tubular bones; Abnormal cartilage collagen on EMKeratan sulfaturia in some patients]; #183900:SED congenita[Dwarfism, short-trunk, identifiable at birthFinal adult height, 84-128cm; Specific growth curves are available; Flat faceMalar hypoplasia; MyopiaRetinal detachmentVitreoretinal degeneration; Cleft palate; Respiratory distressRestrictive lung disease; Barrel chest; Pectus carinatum; PlatyspondylyShort neckOdontoid hypoplasiaKyphosisScoliosisLumbar lordosisOvoid vertebral bodies; Dislocation of hipCoxa varaAbsent pubic ossification in infancy; Flattened epiphysesDiminished joint mobility at elbows, knees, and hips; Talipes equinovarusAbsent talus and calcaneal ossification in infancy; Cervical myelopathyHypotonia]; #184250:SMED Strudwick type[Dwarfism, short-trunk, short-limbed; Myopia; Cleft palate; Pectus carinatum; Anteriorly splayed ribs; Protuberant abdomen; Inguinal hernia; LordosisPlatyspondylyScoliosisOdontoid hypoplasiaC1-C2 subluxation; Delayed pubic bone ossificationCoxa varaHypoplastic pubic bonesNarrow sacrosciatic notches; Generalized epiphyseal delay (infancy)Metaphyseal irregularity and sclerosis (childhood)Club-shaped proximal femurs (infancy)Genu valgaDappled metaphyses (proximal femora, proximal humeri, distal radii, distal ulnae, and proximal and distal tibiae and fibulae)Dappling greater in ulna than radius and fibula greater than tibia; Brachydactyly; Pes planus; Normal intelligence; Caused by mutation in the collagen II, alpha-1 polypeptide gene (COL2A1,)]; #200610:Achondrogenesis, type II or hypochondrogenesis[Dwarfism, marked micromelic; Cleft palate; Cystic hygroma; Barrel-shaped chestShort trunk; Short, horizontal ribsNormal clavicles; Distended abdomen; Enlarged calvaria with normal ossification; Absent vertebral body mineralization; Non-ossified sacrum, ischial, and pubic bonesSmall iliac wings with concave inferior and medial margin; Very short, broad tubular bonesFlared, cupped metaphyses; Short tubular bones; Non-ossified talus and calcaneusShort tubular bones; Fetal hydrops; Polyhydramnios; Stillborn or death shortly after birth]; #215150:Otospondylomegaepiphyseal dysplasia[Short stature; Small jawMidface hypoplasia; Sensorineural hearing lossMixed hearing loss; No ocular symptoms; Anteverted naresBulbous nasal tip; Cleft palatePierre-Robin sequence; Recurrent pulmonary infections; Epiphyseal dysplasia; Mandibular hypoplasia; Increased lumbar lordosisVertebral coronal clefts (newborn)Enlarged odontoid (childhood)Platyspondyly (childhood)Anterior vertebral wedging (childhood); Square iliac wings; Premature osteoarthritisJoint contracturesJoint painsEnlarged JointsDumbbell-shaped femurs (newborn)Short long bonesAbsent-small capital femoral epiphyses (infancy-early childhood)Wide flat epiphysesMetaphyseal flaring; Short handsShort fingersShort metacarpalsProminent interphalangeal joints; Large tarsal bones]; #271700:Spondyloperipheral dysplasia[Short stature; ' Pugilistic facies&aposMidface hypoplasia; Hearing loss, sensorineural; Pectus carinatumBarrel-shaped chest; Spondyloepiphyseal dysplasia; Platyspondyly, mildBiconcave disc (fish-mouth vertebrae)Kyphosis; Short iliaHorizontal acetabulaeFlattened capital femoral epiphysesAcetabular spurs (infancy); Short ulnaAbsent styloid processesLimited elbow extension; Short fingersBroad handsVery short distal phalanges (2nd, 3rd, 4th, 5th)Short metacarpals (2nd, 3rd, 4th, 5th)Cone-shaped epiphysesShort, broad thumbsBrachydactyly E-like changesShort proximal and middle phalanges; Short feetShort phalangesShort metatarsals (4th); Caused by mutation in the collagen II, alpha-1 polypeptide gene (COL2A1,)]; #604864:Osteoarthritis with mild chondrodysplasia[Decreased height compared to unaffected siblings; Osteoarthritis (hips, knees, shoulders, wrists, hands)Joint stiffness; Irregular endplatesMild platyspondylySchmorl' s nodesAnterior wedging; Enlarged MCP jointsEnlarged PIP and DIP jointsHeberden' s nodes]; #608805:Avascular necrosis of the femoral head[Generalized osteoporosis (in some patients); Mild scoliosis (in some patients); Degeneration of hip jointNarrowing of joint space; Avascular necrosis of the femoral headCystic changes of femoral headSclerosis of femoral headNecrosis of bone and marrow tissue on histopathology]; #609162:Czech dysplasia[Normal stature; Mild platyspondylyIrregular vertebral endplatesNarrow intervertebral disc spacesRectangular lumbar spinal canalAccentuated thoracic kyphosisScoliosisElongated vertebrae; Coxa varaIrregular, sclerotic acetabulaeFlattened capital femoral epiphysesNarrow iliac wingsNarrow, short femoral neckProminent trochanterFlexion contractures (hip); ArthralgiaFlexion contractures (knee)Osteochondromatosis (knee); Short metacarpals (4th-5th); Hypoplastic or dysplastic toes (3rd, 4th, and 5th)Hypoplastic metatarsals (3rd and 4th)]; #609508:Stickler sydrome, type I, nonsyndromic ocular[<omim version=1.0><clinicalSynopsisList>]; #616583:Spondyloepiphyseal dysplasia, Stanescu type[Normal height; Limited mouth opening (in some patients); Neck stiffness; ' Z' -posture (due to hip and knee flexion)Accumulation of glycoprotein in chondrocytes; StiffnessKyphoscoliosisPlatyspondylyAnterior wedging; Hypoplastic iliaFlat acetabulumCoxa valga; Joint stiffnessJoint painJoint space narrowingFlexion contractures, especially at hip and kneeEpiphyseal flattening of long bonesMetaphyseal splaying or irregularityFlattened and irregular femoral headBroadening of proximal femoraElongation of proximal femora (in some patients); Prominent metaphysesContractures of finger joints]; #:Vitreoretinopathy with phalangeal epiphyseal dysplasia
Publications
Phenotypes for gene: COL2A1 were changed from Stickler syndrome, type I, 108300 to Stickler syndrome, type I, OMIM:108300
Tag for-review was removed from gene: COL2A1.
Source Expert Review Green was added to COL2A1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag for-review tag was added to gene: COL2A1.
Gene: col2a1 has been classified as Amber List (Moderate Evidence).
Mode of inheritance for gene: COL2A1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: COL2A1 were set to
Phenotypes for gene: COL2A1 were changed from Stickler syndrome, type I, 108300Kniest dysplasia, 156550Achondrogenesis, type II or hypochondrogenesis, 200610SED congenita, 183900SMED Strudwick type, 184250Epiphyseal dysplasia, multiple, with myopia and deafness, 132450Spondyloperipheral dysplasia, 271700SED, Namaqualand typeOsteoarthritis with mild chondrodysplasia, 604864Vitreoretinopathy with phalangeal epiphyseal dysplasiaPlatyspondylic skeletal dysplasia, Torrance type, 151210Otospondylomegaepiphyseal dysplasia, 215150Avascular necrosis of the femoral head, 608805Legg-Calve-Perthes disease, 150600Stickler sydrome, type I, nonsyndromic ocular, 609508Czech dysplasia, 609162; ticklersyndrome,typeI,108300Kniestdysplasia,156550Achondrogenesis,typeIIorhypochondrogenesis,200610SEDcongenita,183900 to Stickler syndrome, type I, 108300
COL2A1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen,Expert
COL2A1 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Radboud University Medical Center, Nijmegen,Expert