Deafness and congenital structural abnormalities
Gene: FGFR3Comment when marking as ready: Associated with phenotypes in OMIM and G2P / DD. Numerous variants reported in the different relevant phenotypes.Created: 14 Sep 2016, 2:12 p.m.
Comment on phenotypes: Also associated with Bladder cancer, somatic 109800, CATSHL syndrome 610474, Cervical cancer, somatic 603956, Colorectal cancer, somatic 114500, Nevus, epidermal, somatic 162900 and Spermatocytic seminoma, somatic 273300Created: 14 Sep 2016, 2:07 p.m.
Achondroplasia; CATSHL syndrome; Crouzon syndrome with acanthosis nigricans; Hypochondroplasia; LADD syndrome; Muenke syndrome; Nevus, epidermal, somatic; SADDAN; Thanatophoric dysplasia, type I; Thanatophoric dysplasia, type IICreated: 13 Sep 2016, 9:11 a.m.
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Green on the Bilateral Microtia Version 1.10 panel.Created: 12 Sep 2016, 2:48 p.m.
Comment on list classification: Green on the Bilateral Microtia Version 1.10 panel.Created: 12 Sep 2016, 2:20 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
#100800:Achondroplasia [Short-limb dwarfism identifiable at birth; Mean male adult height, 131 cm; Mean female height, 124 cm; Frontal bossing; Megalencephaly; Midface hypoplasia; Recurrent otitis media in infancy and childhood; Conductive hearing loss; Low nasal bridge; Upper airway obstruction; Generalized joint laxity; Jugular bulb dehiscence (in some patients); Foramen magnum stenosis; Lumbar kyphosis in infancy; Exaggerated lumbar lordosis during childhood and adulthood; Congenital spinal stenosis due to short pedicles, especially lumbar; Progressive interpediculate narrowing in lumbar spine; Dysplastic ilium; Narrow sacroiliac groove; Flat rooted acetabulae; Bowing of legs; Rhizomelic shortening; Short femoral neck; Metaphyseal flaring; Limited elbow and hip extension; Brachydactyly; Trident hand; Hydrocephalus, occasional; Hypotonia in infancy and early childhood; Brain stem compression; Delayed 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 childhood; Final height, 125 to 160 cm; Macrocephaly; Mild frontal bossing; Normal/mild midface hypoplasia; Variable lumbar lordosis; Progressive narrowing of interpediculate distance in the lumbar vertebrate; Short, squared ilia; Shortened limbs; Short tubular bones with mild metaphyseal flare; Limited extension at elbows; Genu varum; Bowleg; Lack of trident hand helps distinguish it from achondroplasia; Brachydactyly; Occasional mental retardation]; #149730:LADD syndrome [Broad forehead; Simple, cup-shaped ears; Hearing loss, mixed conductive-sensorineural; Alacrima (dry eye syndrome); Nasolacrimal duct obstruction; Aplastic/hypoplastic lacrimal puncta; Aplastic/hypoplastic lacrimal glands; Hypertelorism; Telecanthus; Downslanting palpebral fissures; Dacryocystitis; Partially reduced visually acuity; Recurrent corneal ulcerations; Corneal perforation; Limbal stem cell deficiency; Corneal sensitivity impairment (hypesthesia); Absent Stensen duct; Absent parotid gland; Dry mouth; Oral candidiasis; Hypodontia; Peg-shaped incisors; Enamel hypoplasia; Delayed eruption of primary teeth; Dental caries, severe; Coronal hypospadias; Renal agenesis; Nephrosclerosis; Short radius; Short ulna; Preaxial polydactyly; Digitalized thumb; Triphalangeal thumb; Thenar muscle hypoplasia; Syndactyly, 2-3 finger; Clinodactyly, 3,5 finger; Bifid thumb; Broad halluces; Syndactyly, 2-3, 3-4 toe]; #162900:Nevus, epidermal, somatic [Multiple nevi; Pigmented moles; Woolly 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)]; #187600:Thanatophoric dysplasia, type I [Dwarfism, lethal micromelic; Severe growth deficiency in survivors; Frontal bossing; Macrocephaly; Small face; Respiratory insufficiency/failure; Narrow thorax; Wide-cupped costochondral junctions; Small abnormally formed scapulae; Short ribs; Small foramen magnum; Cloverleaf skull rarely; Severe platyspondyly; Short and small iliac bones; Small sacroiliac notches; Marked shortness and bowing of long bones; ' French telephone receiver femurs' Flared and irregular metaphyses; Temporal lobe heterotopias; Hydrocephalus; Profound 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 junctions; Small abnormally formed scapula; Short ribs; Severe cloverleaf skull (Kleeblattschaedel); Small foramen magnum; Platyspondyly; Short and small iliac bones; Small sacroiliac notches; Straight femurs; Flared 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 -; Seminoma; Nonseminoma (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; Brachycephaly; Macrocephaly; Plagiocephaly; Midface hypoplasia; Low-set frontal hairline; Hearing loss, sensorineural; Hypertelorism; Downslanting palpebral fissures; Ptosis; High-arched palate; Coronal craniosynostosis (unicoronal or bicoronal, unilateral or bilateral); Bulging of temporal fossae; Clinodactyly; Brachydactyly; Coned epiphyses; Broad, thimble-like middle phalanges; Capitate-hamate fusions; Broad halluces; Short middle phalanges; Calcaneocuboidal fusions; Coned epiphyses; Low-set frontal hairline; Developmental delay; Mental 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; Scoliosis; Tall vertebral bodies; Broad femoral metaphyses; Osteochondroma; Long limbs; Lateral deviation of tibiae (1 family); Camptodactyly; Arachnodactyly; Camptodactyly; Developmental delay; Mental retardation (in some patients)]; #612247:Crouzon syndrome with acanthosis nigricans [Brachycephaly; Midface hypoplasia; Proptosis; Hypertelorism; Choanal atresia; Ovarian cysts (in some patients); Craniosynostosis; Acanthosis nigricans (neck, axilla, groin, periorbital region, perioral region); Verrucous hyperplasia; Hyperpigmentation; Hypopigmentation of surgical scars; Melanocytic nevi; Skin hypertrophy, particularly in flexural areas; Generalized skin thickening (particularly over the trunk); Warty acanthomas; Papillomatosis with overlying thin, slightly hyperpigmented epidermis; Hydrocephalus (in some patients)]; #616482:SADDAN [Dwarfism; Short stature, severe disproportionate; Megalencephaly; Large anterior fontanel; Midface hypoplasia; Frontal bossing; Hearing loss, mild-to-moderate; Otitis 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 birth; Sleep apnea; Small chest with flaring costal margins; Gastroesophageal reflux (in some patients); Overgrowth of mandible in adults; Pneumatization of the sinuses; Platyspondyly; Kyphosis; Lumbar lordosis; Cervical spinal stenosis; Posterior rotation of hips; Rhizomelia; Mesomelia; Anterior bowing of femora; Posterior bowing of tibiae; Redundant skin folds on upper and lower limbs; Acanthosis nigricans; Seizures; Hydrocephalus; Central apnea; Developmental delay; Limited language acquisition; Mental retardation, moderate to profound; Thin corpus callosum]
Publications
MIM 134934Created: 3 Feb 2016, 5 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Causes LADD syndrome (lacrimo auriculo dento digital); syndromic features
Publications
26th Oct 2016: the panels Bilateral microtia version 1.10, Ear malformations with hearing impairment version 0.105, and familial hemifacial microsomia version 0.149 gene panels were combined to create this panel. The panel was revised due to expert review, further curation of evidence and internal clinical evaluation. Ready for promotion to version 1.
FGFR3 was added to Deafness and congenital structural abnormalitiespanel. Source: Emory Genetics Laboratory FGFR3 was added to Deafness and congenital structural abnormalitiespanel. Source: Radboud University Medical Center, Nijmegen FGFR3 was added to Deafness and congenital structural abnormalitiespanel. Source: UKGTN Model of inheritance for gene FGFR3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
FGFR3 was added to Deafness and congenital structural abnormalitiespanel. Sources: Expert list,Expert Review Green
FGFR3 was created by sleigh