Monogenic hearing loss
Gene: FGFR3
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
#100800:Achondroplasia[Short-limb dwarfism identifiable at birthMean male adult height, 131 cmMean female height, 124 cm; Frontal bossingMegalencephaly; Midface hypoplasia; Recurrent otitis media in infancy and childhoodConductive hearing loss; Low nasal bridge; Upper airway obstruction; Generalized joint laxity; Jugular bulb dehiscence (in some patients)Foramen magnum stenosis; Lumbar kyphosis in infancyExaggerated lumbar lordosis during childhood and adulthoodCongenital spinal stenosis due to short pedicles, especially lumbarProgressive interpediculate narrowing in lumbar spine; Dysplastic iliumNarrow sacroiliac grooveFlat rooted acetabulae; Bowing of legsRhizomelic shorteningShort femoral neckMetaphyseal flaringLimited elbow and hip extension; BrachydactylyTrident hand; Hydrocephalus, occasionalHypotonia in infancy and early childhoodBrain stem compressionDelayed motor development]; #109800:Bladder cancer, somatic[Transitional cell bladder carcinoma]; #114500:Colorectal cancer, somatic[Hereditary nonpolyposis colorectal carcinoma; Associated endometrial carcinoma, atypical endometrial hyperplasia, uterine leiomyosarcoma, bladder transitional carcinoma, gastric, biliary and renal cell carcinoma; APC, RAS, DCC or KRAS gene mutations; Allele loss on chromosomes 5, 6, 12q, 15, 17, 18, or 22]; #146000:Hypochondroplasia[Short-limb dwarfism identifiable during childhoodFinal height, 125 to 160 cm; MacrocephalyMild frontal bossing; Normal/mild midface hypoplasia; Variable lumbar lordosisProgressive narrowing of interpediculate distance in the lumbar vertebrate; Short, squared ilia; Shortened limbsShort tubular bones with mild metaphyseal flareLimited extension at elbowsGenu varumBowleg; Lack of trident hand helps distinguish it from achondroplasiaBrachydactyly; Occasional mental retardation]; #149730:LADD syndrome[Broad forehead; Simple, cup-shaped earsHearing loss, mixed conductive-sensorineural; Alacrima (dry eye syndrome)Nasolacrimal duct obstructionAplastic/hypoplastic lacrimal punctaAplastic/hypoplastic lacrimal glandsHypertelorismTelecanthusDownslanting palpebral fissuresDacryocystitisPartially reduced visually acuityRecurrent corneal ulcerationsCorneal perforationLimbal stem cell deficiencyCorneal sensitivity impairment (hypesthesia); Absent Stensen ductAbsent parotid glandDry mouthOral candidiasis; HypodontiaPeg-shaped incisorsEnamel hypoplasiaDelayed eruption of primary teethDental caries, severe; Coronal hypospadias; Renal agenesisNephrosclerosis; Short radiusShort ulna; Preaxial polydactylyDigitalized thumbTriphalangeal thumbThenar muscle hypoplasiaSyndactyly, 2-3 fingerClinodactyly, 3,5 fingerBifid thumb; Broad hallucesSyndactyly, 2-3, 3-4 toe; Caused by mutation in the fibroblast growth factor receptor 2 gene (FGFR2,)Caused by mutation in the fibroblast growth factor receptor 3 gene (FGFR3,)Caused by mutation in the fibroblast growth factor 10 gene (FGF10,)]; #162900:Nevus, epidermal, somatic[Multiple neviPigmented molesWoolly hair nevus (in some patients)Hyperpigmented patches of skin (in some patients)Raised, scaly, and/or hyperkeratotic areas of skin (in some patients); Patches of tightly curled scalp hair adjacent to straight hair (in some patients); Caused by somatic mutation in the neuroblastoma RAS viral (v-ras) oncogene homolog gene (NRAS,)Caused by somatic mutation in the phosphatidylinositol 3-kinase, catalytic, alpha polypeptide gene (PIK3CA,)Caused by somatic mutation in the fibroblast growth factor receptor-3 gene (FGFR3,)Caused by somatic mutation in the Harvey rat sarcoma viral (v-Ha-ras) oncogene homolog gene (HRAS,)]; #187600:Thanatophoric dysplasia, type I[Dwarfism, lethal micromelic; Severe growth deficiency in survivors; Frontal bossingMacrocephaly; Small face; Respiratory insufficiency/failure; Narrow thorax; Wide-cupped costochondral junctionsSmall abnormally formed scapulaeShort ribs; Small foramen magnumCloverleaf skull rarely; Severe platyspondyly; Short and small iliac bonesSmall sacroiliac notches; Marked shortness and bowing of long bones' French telephone receiver femurs&aposFlared and irregular metaphyses; Temporal lobe heterotopiasHydrocephalusProfound mental retardation and hypotonia in survivors; Prenatal diagnosis by ultrasound; Decreased fetal activity; Polyhydramnios]; #187601:Thanatophoric dysplasia, type II[Dwarfism, lethal micromelic; Clover leaf head; Small face; Respiratory insufficiency; Narrow thorax; Wide-cupped costochondral junctionsSmall abnormally formed scapulaShort ribs; Severe cloverleaf skull (Kleeblattschaedel)Small foramen magnum; Platyspondyly; Short and small iliac bonesSmall sacroiliac notches; Straight femursFlared and irregular metaphyses; Brachydactyly; Prenatal diagnosis by ultrasound; Decreased fetal activity; Polyhydramnios]; #273300:Spermatocytic seminoma, somatic[Painless testicular mass; Male germ cell tumors (GCT), 2 subtypes -SeminomaNonseminoma (embryonal carcinoma, teratoma, choriocarcinoma, endodermal sinus tumor); Isochromosome 12p (i(12p))Elevated hCG (choriocarcinoma)Elevated AFP (endodermal sinus tumor)Elevated hCG or AFP or both (embryonal carcinoma)Azoospermia/oligospermia (present at diagnosis)]; #602849:Muenke syndrome[Normal height; BrachycephalyMacrocephalyPlagiocephaly; Midface hypoplasiaLow-set frontal hairline; Hearing loss, sensorineural; HypertelorismDownslanting palpebral fissuresPtosis; High-arched palate; Coronal craniosynostosis (unicoronal or bicoronal, unilateral or bilateral)Bulging of temporal fossae; ClinodactylyBrachydactylyConed epiphysesBroad, thimble-like middle phalangesCapitate-hamate fusions; Broad hallucesShort middle phalangesCalcaneocuboidal fusionsConed epiphyses; Low-set frontal hairline; Developmental delayMental retardation]; #603956:Cervical cancer, somatic[<omim version=1.0><clinicalSynopsisList>]; #610474:CATSHL syndrome[Tall stature (male mean adult height 195.6cm, female mean adult height 177.8cm); Microcephaly; Hearing loss, sensorineural; High-arched palate (in some patients); Pectus excavatum; ScoliosisTall vertebral bodies; Broad femoral metaphysesOsteochondromaLong limbsLateral deviation of tibiae (1 family); CamptodactylyArachnodactyly; Camptodactyly; Developmental delayMental retardation (in some patients)]; #612247:Crouzon syndrome with acanthosis nigricans[Brachycephaly; Midface hypoplasia; ProptosisHypertelorism; Choanal atresia; Ovarian cysts (in some patients); Craniosynostosis; Acanthosis nigricans (neck, axilla, groin, periorbital region, perioral region)Verrucous hyperplasiaHyperpigmentationHypopigmentation of surgical scarsMelanocytic neviSkin hypertrophy, particularly in flexural areasGeneralized skin thickening (particularly over the trunk)Warty acanthomas; Papillomatosis with overlying thin, slightly hyperpigmented epidermis; Hydrocephalus (in some patients)]; #616482:SADDAN[DwarfismShort stature, severe disproportionate; MegalencephalyLarge anterior fontanel; Midface hypoplasiaFrontal bossing; Hearing loss, mild-to-moderateOtitis media; Exotropia (in some patients)High myopia (in some patients); Depressed nasal bridge; Congestive heart failure (in some patients); Pulmonary hypertension (in some patients); Respiratory compromise at birthSleep apnea; Small chest with flaring costal margins; Gastroesophageal reflux (in some patients); Overgrowth of mandible in adultsPneumatization of the sinuses; PlatyspondylyKyphosisLumbar lordosisCervical spinal stenosis; Posterior rotation of hips; RhizomeliaMesomeliaAnterior bowing of femoraPosterior bowing of tibiae; Redundant skin folds on upper and lower limbsAcanthosis nigricans; SeizuresHydrocephalusCentral apneaDevelopmental delayLimited language acquisitionMental retardation, moderate to profoundThin corpus callosum]
Publications
FGFR3 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,Expert
FGFR3 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory,Expert